Thomas E. Hughes
Department of Pharmacy, National Institutes of Health Clinical Center, Bethesda, Maryland
All information has been obtained from the current product labeling as of June 1, 2004.
NOTES AND ABBREVIATIONS
Single-agent Dose
The doses listed for each agent are from the package inserts and apply when the agent is given alone, unless otherwise noted.
The doses are expressed in accordance with the nomenclature guidelines from Kohler et al. (1).
Abbreviations Listed under Adverse Reactions
ALDESLEUKIN (PROLEUKIN)
Mechanism of Action
Aldesleukin activates cellular immunity.
P.602
U.S. Food and Drug Administration–Approved Indications
Metastatic renal cell carcinoma and metastatic melanoma
U.S. Food and Drug Administration–Approved Dosage
Dose Modification Criteria
In the event of toxicity a dose may be withheld or interrupted.
Adverse Reactions
CNS: confusion, somnolence, anxiety, and dizziness; CV: hypotension, tachycardia, and arrhythmia; DERM: rash and pruritus; GI: diarrhea, N/V L3, mucositis, and anorexia; GU: oliguria and acute renal failure; HEMAT: myelosuppression; PULM: dyspnea and pulmonary edema; OTHER: pain, fever, chills, and malaise.
Comments
ALEMTUZUMAB (CAMPATH)
Mechanism of Action
Alemtuzumab is a humanized monoclonal antibody directed against the cell surface protein, CD52. The CD52 antigen is expressed on the surface of normal and malignant B and T lymphocytes, natural killer (NK) cells, monocytes, macrophages, and a subpopulation of granulocytes. The proposed mechanism of action of alemtuzumab is the antibody-dependent lysis of leukemic cells following binding to the cell surface.
U.S. Food and Drug Administration–Approved Indications
B-cell chronic lymphocytic leukemia (CLL): It is used for second-line therapy in patients who have been treated with alkylating agents and in those who have failed fludarabine therapy.
U.S. Food and Drug Administration–Approved Dosage
P.603
Dose Modification Criteria
Dose to be modified in cases of myelosuppression.
Adverse Reactions
CNS: headache, dysthesia, and dizziness; CV: hypotension and edema or peripheral edema; DERM: rash, urticaria, and pruritus; GI: N/V L2–3, diarrhea, anorexia, and mucositis or stomatitis; HEMAT: myelosuppression and lymphopenia; INFUS: rigors, fever, chills, N/VL2–3, hypotension, dyspnea, bronchospasm, headache, rash, and urticaria; PULM: dyspnea, cough, bronchitis, pneumonia, and bronchospasm; OTHER: opportunistic infections, sepsis, fatigue, asthenia, and pain.
Comments
ALTRETAMINE (HEXALEN)
Mechanism of Action
Altretamine has an unknown mechanism of action, but structure is similar to an alkylating agent.
U.S. Food and Drug Administration–Approved Indications
Ovarian cancer: second-line therapy; palliative therapy for persistent or recurrent ovarian cancer
U.S. Food and Drug Administration–Approved Dosage
65 mg per m2 PO q.i.d. (4 times daily; total daily dose: 260 mg per m2) for 14 or 21 consecutive days, every 28 days
Dose Modification Criteria
Dose modified in case of myelosuppression and nonhematologic toxicity (i.e., GI intolerance and progressive neurotoxicity).
P.604
Adverse Reactions
CNS: peripheral sensory neuropathy, mood disorders, ataxia, and dizziness; GI: N/V L3; HEMAT: myelosuppression [white blood cells (WBCs), red blood cells (RBCs), platelets].
Comments
Patients to be monitored for neurologic toxicity
ANASTROZOLE (ARIMIDEX)
Mechanism of Action
Anastrozole is a selective, nonsteroidal aromatase inhibitor.
U.S. Food and Drug Administration–Approved Indications
Breast Cancer:
U.S. Food and Drug Administration–Approved Dosage
1 mg PO daily (no requirement for glucocorticoid or mineralocorticoid replacement therapy)
Dose Modification Criteria
Renal impairment: no dose modification; hepatic impairment (mild to moderate): no dose modification; hepatic impairment (severe): no data available
Adverse Reactions
CNS: headache; CV: hot flashes/flushing; GI: nausea, diarrhea, and elevated LFT values (in patients with liver metastases); PULM: dyspnea; OTHER: asthenia, pain, back pain, and vaginal bleeding.
Comments
Patients with estrogen-receptor (ER)–negative disease and patients who do not respond to tamoxifen rarely respond to anastrozole.
ARSENIC TRIOXIDE (TRISENOX)
Mechanism of Action
The mechanism of action of arsenic trioxide is not completely defined. It induces apoptosis in NB4 human promyelocytic leukemia cells in vitro and damages or degrades the fusion protein PML/RAR α.
P.605
U.S. Food and Drug Administration–Approved Indications
Acute promyelocytic leukemia (APL): second-line therapy for the induction of remission and for consolidation of APL patients who are refractory to, or have relapsed from, retinoid and anthracycline chemotherapy.
U.S. Food and Drug Administration–Approved Dosage
Dose Modification Criteria
Renal impairment: no data available (use with caution); hepatic impairment: no data available.
Adverse Reactions
CNS: headache, dizziness, and paresthesias; CV: QT interval prolongation, complete atrioventricular block, torsade de pointes–type ventricular arrhythmia, atrial dysrhythmias, tachycardia, hypotension, and edema; DERM: rash, dermatitis, dry skin, and pruritus; ENDO: hyperglycemia, hypokalemia, and hypomagnesemia; GI: N/V L3, diarrhea, abdominal pain, anorexia, constipation, and elevated LFT values; HEMAT: leukocytosis and myelosuppression; PULM: dyspnea and cough; OTHER: fatigue, arthralgia, myalgia, pain, and APL differentiation syndrome or retinoic acid acute promyelocytic leukemia (RA-APL) syndrome (RA-APL syndrome: fever, dyspnea, weight gain, radiographic pulmonary infiltrates, and pleural or pericardial effusion).
Comments
ASPARAGINASE (ELSPAR)
Mechanism of Action
Asparaginase depletes asparagine, an amino acid required by some leukemic cells.
P.606
U.S. Food and Drug Administration–Approved Indications
For acute lymphoblastic leukemia (ALL): induction therapy with asparaginase (primarily in combination with other agents)
U.S. Food and Drug Administration–Approved Dosage
Dose Modification Criteria
No data available
Adverse Reactions
DERM: skin rash; ENDO: hyperglycemia; GI: N/V L2, pancreatitis, increased LFT values, increased bilirubin levels, and decreased serum albumin; GU: prerenal azotemia; HEMAT: coagulopathy; CNS: a variety of changes in mental status; OTHER: hypersensitivity, anaphylactic reactions, and hyperthermia.
Comments
AZACITIDINE (VIDAZA)
Mechanism of Action
Azacitidine is an antimetabolite; a pyrimidine nucleoside analog of cytidine. It causes hypomethylation of deoxyribonucleic acid (DNA) and produces direct cytotoxicity on abnormal hematopoietic cells in the bone marrow.
U.S. Food and Drug Administration–Approved Indications
Myelodysplastic syndrome (MDS): The specific subtypes of MDS for which azacitidine is indicated include refractory anemia or refractory anemia with ringed sideroblasts (if accompanied by neutropenia or thrombocytopenia or when tranfusions are required), refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia.
U.S. Food and Drug Administration–Approved Dosage
P.607
Dose Modification Criteria
Renal impairment: no data available (to be used with caution); Hepatic: no data available (to be used with caution); Myelosuppression: dose to be modified; nonhematologic toxicity (i.e., renal tubular acidosis and renal toxicity): dose to be modified.
Adverse Reactions
CNS: headache and dizziness; DERM: injection-site erythema or pain, ecchymosis, rash, and pruritus; ELECTRO: renal tubular acidosis (i.e., alkaline urine, fall in serum bicarbonate concentration, and hypokalemia); GI: N/V L1, diarrhea, constipation, anorexia, abdominal pain, and hepatotoxicity; GU: increased Cr and blood urea nitrogen (BUN) concentration, and renal failure; HEMAT: anemia, neutropenia, and thrombocytopenia; PULM: cough and dyspnea; OTHER: fever, rigors, fatigue, weakness, and peripheral edema.
Comments
BACILLE CALMETTE-GUÉRIN LIVE (INTRAVESICAL) (THERACYS, TICE BCG)
Mechanism of Action
Bacille Calmette-Guérin has local inflammatory and immune response effect.
U.S. Food and Drug Administration–Approved Indications
Treatment and prophylaxis of carcinoma in situ of the urinary bladder and for the prophylaxis of primary or recurrent stage Ta and/or T1 papillary tumors following transurethal resection (TUR).
U.S. Food and Drug Administration–Approved Dosage
One reconstituted vial (81 mg per 3 mL), diluted in 50 mL of sterile, preservative-free normal saline (0.9% sodium chloride injection), is instilled into bladder for as long as possible (for up to 2 hours) once weekly for 6 weeks (induction therapy), followed by one treatment at 3, 6, 12, 18, and 24 months each after the initial treatment (maintenance therapy).
One reconstituted vial (50 mg per mL), diluted in a total volume of 50-mL preservative-free normal saline (0.9% sodium chloride injection), is instilled into bladder for as long as possible (for up to 2 hours) once weekly for 6 weeks, followed by once monthly for 6 to 12 months.
Dose Modification Criteria
Withhold Bacille Calmette-Guérin (BCG) live in case of any suspicion of systemic infection.
P.608
Adverse Reactions
CNS: malaise, fever, and chills; GU: irritative bladder symptoms; OTHER: infectious complications (uncommon).
Comments
BEVACIZUMAB (AVASTIN)
Mechanism of Action
Bevacizumab is a recombinant humanized monoclonal immunoglobulin (Ig)G1 antibody that binds to and inhibits the biologic activity of human vascular endothelial growth factor (VEGF).
U.S. Food and Drug Administration–Approved Indications
Metastatic carcinoma of the colon or rectum: first-line therapy in combination with intravenous 5-fluorouracil–based chemotherapeutic agents.
U.S. Food and Drug Administration–Approved Dosage
Dose Modification Criteria
Renal impairment: no dose modification; hepatic impairment: no dose modification; myelosuppression: no dose modification; nonhematologic toxicity: dose to be modified.
Adverse Reactions
CNS: headache; CV: hypertension, hypertensive crisis, and CHF; GI: N/VL1, diarrhea, abdominal pain, gastrointestinal perforation, and wound dehiscence; GU: proteinuria and nephrotic syndrome; INFUS: fever, chills, wheezing, and stridor; PULM: dyspnea and wheezing stridor; OTHER: epistaxis and other mild to moderate hemorrhagic events, serious hemorrhagic events, wound healing complications, deep vein thrombosis or other thromboembolic events, and asthenia.
Comments
P.609
BEXAROTENE (TARGRETIN)
Mechanism of Action
Bexarotene is a retinoid that selectively binds and activates retinoid X receptor (RXR) subtypes. Once activated, these receptors function as transcription factors that regulate the expression of genes that control cellular differentiation and proliferation.
U.S. Food and Drug Administration–Approved Indications
Cutaneous T-cell lymphoma (CTCL): second-line therapy for the cutaneous manifestations of CTCL in patients who are refractory to at least one prior systemic therapy
U.S. Food and Drug Administration–Approved Dosage
300 mg per m2 PO daily with a meal
Dose Modification Criteria
Renal impairment: no dose modification (caution as a result of possible protein binding alterations); hepatic impairment: use with caution; toxicity: dose to be modified.
Adverse Reactions
CNS: headache; CV: peripheral edema; DERM: dry skin, photosensitivity, rash, and pruritus; ENDO: hypothyroidism and hypoglycemia (diabetic patients); GI: nausea, pancreatitis, elevated LFT values, and abdominal pain; HEMAT: leukopenia and anemia; OCULAR: cataracts; OTHER: lipid abnormalities (i.e., elevated triglycerides, elevated total and LDL cholesterol, and decreased HDL cholesterol), asthenia, and infection.
Comments
P.610
pregnancy test within 1 week before starting bexarotene therapy, and the test should be repeated at monthly intervals while the patient remains on therapy. Effective contraception (two reliable forms used simultaneously) must be used for 1 month before initiation of therapy, during therapy, and for at least 1 month following discontinuation of therapy. Bexarotene may induce the metabolism of hormonal contraceptives and reduce their effectiveness; therefore, one form of contraception should be nonhormonal.
BICALUTAMIDE (CASODEX)
Mechanism of Action
Bicalutamide has antiandrogenic activity.
U.S. Food and Drug Administration–Approved Indications
Palliation of advanced prostate cancer (stage D2) in combination with a luteinizing hormone–releasing hormone (LH-RH) agonist.
U.S. Food and Drug Administration–Approved Dosage
50 mg PO daily
Dose Modification Criteria
Renal impairment: no dose modification; hepatic impairment (mild to moderate): no dose modification; hepatic impairment (severe): use with caution.
Adverse Reactions
ENDO: loss of libido, hot flashes, and gynecomastia; GI: nausea, diarrhea, and constipation; GU: impotence.
Comments
Monitor LFT results before treatment, at regular intervals for the first 4 months, and periodically thereafter.
BLEOMYCIN (BLENOXANE)
Mechanism of Action
The mechanism of action of bleomycin is unknown, but it may inhibit DNA and ribonucleic acid (RNA) synthesis.
U.S. Food and Drug Administration–Approved Indications
Squamous cell cancers, non-Hodgkin lymphoma, testicular cancer, Hodgkin disease, and malignant pleural effusions
U.S. Food and Drug Administration–Approved Dosage
P.611
Dose Modification Criteria
Renal impairment: use with caution (dose modification guidelines are not provided within package insert but are available from other references).
Adverse Reactions
DERM: erythema, rash, striae, vesiculation, hyperpigmentation, skin tenderness, alopecia, nail changes, pruritus, and stomatitis; PULM: pulmonary fibrosis (increases at cumulative doses >400 U, but can occur at lower total doses) and pneumonitis; Other: fever; chills; idiosyncratic reaction consisting of hypotension, mental confusion, fever, chills, and wheezing has been reported in 1% of lymphoma patients; and local pain with intrapleural administration.
Comments
BORTEZOMIB (VELCADE)
Mechanism of Action
Bortezomib is a reversible inhibitor of the 26S proteosome, a large protein complex that degrades ubiquitinated proteins. Inhibition of the 26S proteosome prevents targeted proteolysis, which can effect multiple signaling cascades within the cell. This disruption of normal homeostatic mechanisms can lead to cell death.
U.S. Food and Drug Administration–Approved Indications
Multiple myeloma: second-line therapy in patients with multiple myeloma who have received at least two earlier therapies and have demonstrated disease progression during the last therapy.
U.S. Food and Drug Administration–Approved Dosage
The dosage is 1.3 mg per m2 i.v. as a bolus injection administered twice weekly for 2 weeks (days 1, 4, 8, and 11), followed by a 10-day rest period (days 12 to 21). Three weeks (21 days) is considered to be a treatment cycle. At least 72 hours should elapse between consecutive doses of bortezomib.
Dose Modification Criteria
Renal impairment: no data are available (use with caution); Hepatic impairment: no data are available (use with caution); Myelosuppression: dose to be modified; nonhematologic toxicity (e.g., neuropathy and neuropathic pain): dose to be modified
Adverse Reactions
CNS: peripheral neuropathy, neuropathic pain, dizziness, and headache; CV: hypotension (including orthostatic hypotension and syncope) and edema; DERM: rash; GI: N/V L2–3, diarrhea, anorexia, and constipation; HEMAT: myelosuppression (thrombocytopenia more severe than anemia, which is more severe than neutropenia); OCULAR: diplopia and blurred vision; PULM: dyspnea; OTHER: asthenia, fatigue, fever, insomnia, and arthralgia.
P.612
BUSULFAN (MYLERAN); BUSULFAN INJECTION (BUSULFEX)
Mechanism of Action
Busulfan is an alkylating agent.
U.S. Food and Drug Administration–Approved Indications
U.S. Food and Drug Administration–Approved Dosage
Dose Modification Criteria
Myelosuppression: dose to be modified
Adverse Reactions
CNS: seizures; DERM: hyperpigmentation; GI: N/V oral L1, i.v. L4; HEMAT: severe myelosuppression; HEPATIC: venoocclusive disease (VOD); PULM: pulmonary fibrosis and VOD.
Comments
CAPECITABINE (XELODA)
Mechanism of Action
Capecitabine is an antimetabolite that is enzymatically converted to fluorouracil in tumors.
U.S. Food and Drug Administration–Approved Indications
P.613
U.S. Food and Drug Administration–Approved Dosage
The dosage is 1,250 mg per m2 PO twice daily (total daily dose: 2,500 mg per m2) at the end of a meal for 2 weeks, followed by a 1-week rest period, given as 3-week cycles. Product labeling may be consulted for a dosing chart.
Dose Modification Criteria
Renal (mild impairment; CrCl 51 to 80 mL per minute): no modification to dosage; renal (moderate impairment; CrCl 30 to 50 mL per minute): dosage to be modified; hepatic (mild-to-moderate impairment because of liver metastases): no modification of dosage; toxicity (grade 2 toxicity or higher): dosage to be modified. Product labeling may be consulted for dose modification guidelines.
Adverse Reactions
CNS: fatigue or weakness, paresthesia, and peripheral sensory neuropathy; DERM: hand and foot syndrome (palmar–plantar erythrodysesthesia) and dermatitis; GI: N/V L2, diarrhea, mucositis, abdominal pain, anorexia, and hyperbilirubinemia; HEMAT: myelosuppression.
CARBOPLATIN (PARAPLATIN)
Mechanism of Action
Carboplatin is an alkylating-like agent producing interstrand DNA cross-links.
U.S. Food and Drug Administration–Approved Indications
Advanced ovarian cancer:
U.S. Food and Drug Administration–Approved Dosage
Total dose in milligrams = (target AUC) × [glomerular filtration rate (GFR) + 25].
Dose Modification Criteria
Renal impairment: dosage is to be modified; Myelosuppression: dosage is to be modified.
P.614
Adverse Reactions
CNS: neuropathy; GI: N/V L4, increased LFT values; ELECTRO: Mg, Na, Ca, and K alterations; GU: Increased Cr and BUN; HEMAT: myelosuppression (thrombocytopenia greater than leukopenia and anemia); OTHER: anaphylactic reactions; pain and asthenia.
Comments
Not to be confused with cisplatin for dosing or during preparation.
CARMUSTINE (BICNU)
Mechanism of Action
Carmustine is an alkylating agent.
U.S. Food and Drug Administration–Approved Indications
Indicated as palliative therapy either as a single agent or in established combination therapy with other approved chemotherapeutic agents in the following: brain tumors, multiple myeloma, Hodgkin disease, and non-Hodgkin lymphomas.
U.S. Food and Drug Administration–Approved Dosage
Single agent in previously untreated patients: 150 to 200 mg per m2 i.v. × one dose every 6 weeks, or 75 to 100 mg per m2 i.v. daily × two doses every 6 weeks.
Dose Modification Criteria
Myelosuppression: dosage to be modified.
Adverse Reactions
GI: N/V L5 for dosage >250 mg per m2, and L4 for dosage ≤250 mg per m2; increased LFT values; GU: nephrotoxicity with large cumulative doses; HEMAT: myelosuppression (can be delayed); OCULAR: retinal hemorrhages; PULM: pulmonary fibrosis (acute and delayed).
Comments
Risk of pulmonary toxicity increases with cumulative total doses >1,400 mg per m2 and in patients with a history of lung disease, radiation therapy, or concomitant bleomycin.
CETUXIMAB (ERBITUX)
Mechanism of Action
Cetuximab is a recombinant chimeric monoclonal antibody that binds to the extracellular domain of the human epidermal growth factor receptor (EGFR) on both normal and tumor cells, and competitively inhibits the binding of epidermal growth factor (EGF) and other ligands, thereby blocking the phosphorylation and activation of receptor-associated kinases.
U.S. Food and Drug Administration–Approved Indications
Metastatic colorectal carcinoma (second-line therapy): cetuximab is indicated for use in combination with irinotecan in EGFR-expressing metastatic colorectal carcinoma in patients
P.615
who are refractory to irinotecan-based chemotherapy, and as monotherapy in patients who are intolerant to irinotecan-based chemotherapy.
U.S. Food and Drug Administration–Approved Dosage
In the treatment of metastatic colorectal carcinoma (combined with irinotecan or as monotherapy): 400 mg per m2 i.v. infusion over 120 minutes as an initial loading dose (first infusion) followed by a weekly maintenance dose of 250 mg per m2 i.v. infusion over 60 minutes. Premedication with an H1 antagonist (e.g., 50 mg of diphenhydramine i.v.) is recommended.
Dose Modification Criteria
Renal impairment: no dosage modification; hepatic impairment: no dosage modification; symptoms of non-hematologic toxicity (dermatologic toxicity): dosage to be modified.
Adverse Reactions
DERM: acneform rash, skin drying and fissuring, and nail toxicity; GI: nausea, constipation, and diarrhea; INFUS: chills, fever, dyspnea, airway obstruction (bronchospasm, stridor, hoarseness), urticaria, and hypotension; PULM: interstitial lung disease; OTHER: asthenia, malaise, and fever.
Comments
CHLORAMBUCIL (LEUKERAN)
Mechanism of Action
Alkylating agent
U.S. Food and Drug Administration–Approved Indications
Palliation of CLL, Hodgkin disease, and non-Hodgkin lymphomas
P.616
U.S. Food and Drug Administration–Approved Dosage
Dose Modification Criteria
Myelosuppression: dose to be modified
P.617
Adverse Reactions
CNS: seizures, confusion, twitching, and hallucinations; DERM: rash and rare reports of progressive skin hypersensitivity reactions; GI: N/V L1 and increased LFT values; HEMAT: myelosuppression and lymphopenia; PULM: pulmonary fibrosis; OTHER: allergic reactions, secondary acute myelomonocytic leukemia (AML) (long-term therapy), and sterility.
Comments
Radiation and cytotoxic drugs render the bone marrow more vulnerable to damage; chlorambucil should be used with caution within 4 weeks of a full course of radiation therapy or chemotherapy.
CISPLATIN (PLATINOL)
Mechanism of Action
Cisplatin is an alkylating-like agent that produces interstrand DNA cross-links.
U.S. Food and Drug Administration–Approved Indications
U.S. Food and Drug Administration–Approved Dosage
Dose Modification Criteria
Renal impairment: dose to be modified; myelosuppression: dose to be modified
Adverse Reactions
CNS: neuropathy, paresthesia, and ototoxicity; ELECTRO: Mg, Na, Ca, and K alterations; GI: N/V (for dose ≥50 mg per m2: L5, for dose <50 mg per m2: L4) increased LFT values [especially serum glutamic-oxaloacetic transaminase (ALT), bilirubin]; GU: increased Cr and BUN (cumulative); HEMAT: myelosuppression, and anemia; OCULAR: optic neuritis, papilledema, and cerebral blindness infrequently reported; OTHER: anaphylactic reactions and rare vascular toxicities.
Comments
CLADRIBINE (LEUSTATIN)
Mechanism of Action
Antimetabolite
U.S. Food and Drug Administration–Approved Indications
Hairy cell leukemia
U.S. Food and Drug Administration–Approved Dosage
Dose Modification Criteria
Renal impairment: no data available on dosage modification; hepatic impairment: no data available on dosage modification.
Adverse Reactions
CNS: fatigue, headache, and peripheral neuropathy; GI: N/V L1; HEMAT: myelosuppression and lymphopenia; DERM: rash; OTHER: fever.
Comments
Immunosuppression (lymphopenia) persists for up to 1 year after cladribine therapy.
CYCLOPHOSPHAMIDE (CYTOXAN)
Mechanism of Action
Cyclophosphamide is an alkylating agent that is activated by the liver.
P.618
U.S. Food and Drug Administration–Approved Indications
Lymphomas, leukemias, multiple myeloma, mycosis fungoides (advanced disease), neuroblastoma (disseminated disease), adenocarcinoma of the ovary, retinoblastoma, breast cancer.
U.S. Food and Drug Administration–Approved Dosage
Dose Modification Criteria
Myelosuppression: dose to be modified.
P.619
Adverse Reactions
CNS: syndrome of inappropriate antidiuretic hormone (SIADH); DERM: rash, skin and nail pigmentation, and alopecia; GI: N/V (>1,500 mg per m2: L5, between 750 mg per m2 and 1,500 mg per m2: L4, <750 mg per m2: L3), anorexia, and diarrhea; GU: hemorrhagic cystitis, renal tubular necrosis; HEMAT: myelosuppression (leukopenia greater than thrombocytopenia and anemia); PULM: pulmonary fibrosis; OTHER: secondary malignancies; sterility, amenorrhea; anaphylactic reactions; cardiac toxicity with high-dose regimens.
Comments
Encourage forced fluid intake and frequent voiding to reduce the risk of hemorrhagic cystitis. Use of vigorous intravenous hydration and Mesna therapy with high-dose cyclophosphamide may be considered.
CYTARABINE (CYTOSAR AND OTHERS)
Mechanism of Action
Cytarabine is an antimetabolite.
U.S. Food and Drug Administration–Approved Indications
Induction therapy of acute nonlymphocytic leukemia, (ANLL), in combination with other agents, ALL, blast-phase chronic myelocytic leukemia (CML), intrathecal prophylaxis and treatment of meningeal leukemia.
U.S. Food and Drug Administration–Approved Dosage
Dose Modification Criteria
Hepatic/Renal impairment: To be used with caution and at possibly reduced dose in patients with poor hepatic or renal function (no specific criteria). Neurotoxicity: dose to be modified.
Adverse Reactions
CNS: cerebellar dysfunction, somnolence, coma (generally seen with high-dose regimens), and chemical arachnoiditis (intrathecal administration); DERM: rash and alopecia; GI: N/V L2 (>1 g per m2 L4), anorexia, diarrhea, mucositis, increased LFT values and pancreatitis (in patients who have previously received asparaginase); HEMAT: myelosuppression; OCULAR: conjunctivitis (generally seen with high-dose regimens); OTHER: cytarabine (Ara-C) syndrome (includes fever, myalgia, bone pain, rash, conjunctivitis, and malaise); acute respiratory distress syndrome reported with high-dose regimens.
Comments
CYTARABINE LIPOSOME INJECTION (DEPOCYT)
Mechanism of Action
Cytarabine liposome is an antimetabolite.
U.S. Food and Drug Administration–Approved Indications
Intrathecal treatment of lymphomatous meningitis.
U.S. Food and Drug Administration–Approved Dosage
Dose Modification Criteria
Neurotoxicity: dose to be modified.
Adverse Reactions
CNS: Chemical arachnoiditis, headache, asthenia, confusion, and somnolence.
DACARBAZINE (DTIC-DOME)
Mechanism of Action
Mechanism of dacarbazine is unknown.
U.S. Food and Drug Administration–Approved Indications
Metastatic malignant melanoma, Hodgkin disease (second-line therapy).
P.620
U.S. Food and Drug Administration–Approved Dosage
Adverse Reactions
DERM: alopecia, rash, facial flushing, and facial paresthesia; GI: N/V L5, anorexia, diarrhea, increased LFT values, and hepatic necrosis; OTHER: pain and burning at infusion, anaphylaxis, fever, myalgias, and malaise.
DACTINOMYCIN (COSMEGEN)
Mechanism of Action
Dactinomycin is an intercalating agent.
U.S. Food and Drug Administration–Approved Indications
Indicated as part of a combination chemotherapy or multi-modality treatment regimen for the following malignancies: Wilms tumor; childhood rhabdomyosarcoma; Ewing sarcoma; and metastatic, nonseminomatous testicular cancer. Indicated as a single agent or as part of a combination regimen for gestational trophoblastic neoplasia. Indicated as a component of regional perfusion in the treatment of locally recurrent or locoregional solid malignancies.
U.S. Food and Drug Administration–Approved Dosage
Dose Modification Criteria
Myelosuppression: dose to be modified.
Adverse Reactions
DERM: alopecia, erythema, skin eruptions, radiation recall, and tissue damage or necrosis, with extravasation; ELECTRO: hypocalcemia; GI: N/V (>1.5 mg per m2: L4, ≤1.5 mg per m2: L3), mucositis, anorexia, dysphagia, increased LFT values, and hepatotoxicity; HEMAT: myelosuppression; OTHER: fever, fatigue, myalgia, and secondary malignancies.
Comments
Vesicant
DAUNORUBICIN (CERUBIDINE)
Mechanism of Action
Daunorubicin is an intercalating agent that inhibits topoisomerase-II.
P.621
U.S. Food and Drug Administration–Approved Indications
In adult ANLL or ALL (children and adults) in combination with other agents for remission induction.
U.S. Food and Drug Administration–Approved Dosage
Dose Modification Criteria
Renal impairment: dose to be modified; hepatic: dose is to be modified.
P.622
Adverse Reactions
CV: CHF, (risk of cardiotoxicity increases rapidly with total lifetime cumulative doses >400 to 550 mg per m2 in adults or >300 mg per m2 in children), arrhythmias; DERM: nail hyperpigmentation, rash, alopecia, tissue damage or necrosis, with extravasation; GI: N/V L3, mucositis; HEMAT: myelosuppression; Other: red-tinged urine, fever, chills, and secondary malignancies.
Comments
DAUNORUBICIN CITRATE LIPOSOME INJECTION (DAUNOXOME)
Mechanism of Action
Daunorubicin is an intercalating agent that inhibits topoisomerase-II.
U.S. Food and Drug Administration–Approved Indications
Advanced human immunodeficiency virus (HIV)-associated Kaposi sarcoma (first-line therapy).
U.S. Food and Drug Administration–Approved Dosage
40 mg per m2 i.v. over 60 minutes × one dose every 2 weeks.
Dose Modification Criteria
Hepatic: dose is to be modified; renal impairment: dose is to be modified; myelosuppression: dose is to be modified.
Adverse Reactions
CV: CHF, arrhythmias; DERM: nail, alopecia, hyperpigmentation, and rash; GI: N/V L2, mucositis, and diarrhea; HEMAT: myelosuppression; INFUS: back pain, flushing, and chest tightness (infusion-related reactions usually subside with interruption of the infusion, and generally do not recur if the infusion is then resumed at a slower rate); OTHER: red-tinged urine, fever, chills, and fatigue.
Comments
DENILEUKIN DIFTITOX (ONTAK)
Mechanism of Action
Denileukin diftitox is a fusion protein composed of diphtheria toxin fragments linked to interleukin 2 (IL-2) sequences; interacts with IL-2 cell surface receptors and inhibits cellular protein synthesis.
U.S. Food and Drug Administration–Approved Indications
Treatment of persistent or recurrent CTCL in patients whose malignant cells express the CD25 component of the IL-2 receptor.
U.S. Food and Drug Administration–Approved Dosage
Adverse Reactions
CNS: dizziness; CV: vascular leak syndrome (hypotension and edema hypoalbuminemia), hypotension, and thrombotic events; DERM: rash, pruritus; GI: N/V L3, anorexia, diarrhea, and increased LFT values; HEMAT: anemia; INFUS: acute hypersensitivity-type reactions consisting of one or more of the following: hypotension, back pain, dyspnea, vasodilation, rash, chest pain or tightness, tachycardia, dysphagia, syncope, allergic reactions, or anaphylaxis; PULM: dyspnea and cough; OTHER: flu-like syndrome consisting of one or more of the following: fever and/or chills, asthenia, digestive symptoms, myalgias, and arthralgias (appears several hours to days after dose infusion).
Comments
P.623
DOCETAXEL (TAXOTERE)
Mechanism of Action
Docetaxel has the effect of microtubule assembly stabilization.
U.S. Food and Drug Administration–Approved Indications
U.S. Food and Drug Administration–Approved Dosage
Dose Modification Criteria
Hepatic: dose to be modified; myelosuppression: dose to be modified; nonhematologic toxicity: dose to be modified (package labeling to be consulted for dose modification guidelines)
Adverse Reactions
CNS: peripheral neurosensory toxicity (paresthesia, dysesthesia, and pain), fever, and asthenia; DERM: rash with localized skin eruptions, erythema and pruritus, nail changes (pigmentation, onycholysis, and pain), and alopecia; GI: N/V L2, diarrhea, mucositis, and increased LFT values; HEMAT: myelosuppression; INFUS: acute hypersensitivity-type reactions consisting of hypotension and/or bronchospasm or generalized rash/erythema; OTHER: severe fluid retention and myalgia.
Comments
P.624
DOXORUBICIN (ADRIAMYCIN AND OTHERS)
Mechanism of Action
Doxorubicin is an intercalating agent and inhibits topoisomerase-II.
U.S. Food and Drug Administration–Approved Indications
ALL, acute nonlymphocytic leukemia; Wilms tumor; neuroblastoma; soft tissue and bone sarcoma; breast, ovarian, thyroid, bronchiogenic, gastric cancer and transitional cell bladder cancer; Hodgkin disease; malignant lymphoma.
U.S. Food and Drug Administration–Approved Dosage
Dose Modification Criteria
Hepatic: dose to be modified; myelosuppression: dose to be modified.
Adverse Reactions
CV: CHF, (risk of cardiotoxicity increases rapidly with total lifetime cumulative doses >450 mg per m2) and arrhythmias; DERM: nail hyperpigmentation, onycholysis, alopecia, radiation recall, tissue damage or necrosis with extravasation; GI: N/V (>60 mg per m2: L4, 20 to 60 mg per m2: L3, <20 mg per m2: L2) and mucositis; HEMAT: myelosuppression; OTHER: red-tinged urine, fever, chills, and secondary malignancies.
Comments
Vesicant
DOXORUBICIN HYDROCHLORIDE LIPOSOME INJECTION (DOXIL)
Mechanism of Action
Doxorubicin is an intercalating agent and inhibits topoisomerase-II.
U.S. Food and Drug Administration–Approved Indications
U.S. Food and Drug Administration–Approved Dosage
P.625
Dose Modification Criteria
Hepatic: dose to be modified; Palmar–plantar erythrodysesthesia: dose to be modified; Myelosuppression: dose to be modified; Stomatitis: dose to be modified.
P.626
Adverse Reactions
CV: CHF and arrhythmias; DERM: palmar–plantar erythrodysesthesia, alopecia, and rash; GI: N/V L2, mucositis or stomatitis; HEMAT: myelosuppression; INFUS: flushing, shortness of breath, facial swelling, headache, chills, chest pain, back pain, tightness in chest or throat, fever, tachycardia, pruritus, rash, cyanosis, syncope, bronchospasm, asthma, apnea, and/or hypotension; OTHER: asthenia and red-tinged urine.
Comments
EPIRUBICIN (ELLENCE)
Mechanism of Action
Epirubicin is an intercalating agent and inhibits topoisomerase-II.
U.S. Food and Drug Administration–Approved Indications
Adjuvant therapy of axillary node–positive breast cancer.
U.S. Food and Drug Administration–Approved Dosage
The following dosage regimens were used in the trials supporting use of epirubicin as a component of adjuvant therapy in patients with axillary-node–positive breast cancer.
Dose Modification Criteria
Renal impairment: dose to be modified; hepatic impairment: dose to be modified; myelosuppression: dose to be modified.
Adverse Reactions
CV: CHF (risk of cardiotoxicity increases rapidly with total lifetime cumulative doses >900 mg per m2), arrhythmias; DERM: alopecia, radiation recall, tissue damage or necrosis with extravasation; GI: N/V (>90 mg per m2: L4, ≤90 mg per m2: L3), and mucositis; HEMAT: myelosuppression; OTHER: facial flushing, and secondary malignancies.
Comments
Vesicant
ESTRAMUSTINE (EMCYT)
Mechanism of Action
Estramustine is an alkylating agent, an estrogen, and induces microtubule instability.
U.S. Food and Drug Administration–Approved Indications
Palliative treatment of metastatic and/or progressive carcinoma of the prostate.
U.S. Food and Drug Administration–Approved Dosage
Dose Modification Criteria
Hepatic impairment: to be administered with caution, no specific dose modifications
Adverse Reactions
CV: Edema, fluid retention, and venous thromboembolism; ENDO: hyperglycemia, gynecomastia, and impotence; GI: diarrhea, nausea, and elevated LFT values [especially glutamic-oxaloacetic transaminase (SGOT) or lactate dehydrogenase (LDH)]; PULM: dyspnea.
ETOPOSIDE (VEPESID)
Mechanism of Action
Etoposide leads to topoisomerase-II interaction.
U.S. Food and Drug Administration–Approved Indications
Refractory testicular cancer; small cell lung cancer (SCLC, first-line therapy in combination with other agents).
U.S. Food and Drug Administration–Approved Dosage
P.627
repeated every 3 to 4 weeks (in combination with other approved agents). Current literature may be consulted for dose recommendations.
Dose Modification Criteria
Renal impairment: dose to be modified.
Adverse Reactions
DERM: alopecia, rash, urticaria, and pruritus; GI: N/V L2, mucositis, and anorexia; HEMAT: myelosuppression; INFUS: hypotension (infusion-rate related), anaphylactic-like reactions (characterized by chills, fever, tachycardia, bronchospasm, dyspnea, and/or hypotension); OTHER: secondary malignancies.
P.628
ETOPOSIDE PHOSPHATE (ETOPHOS)
Mechanism of Action
Etoposide phosphate is rapidly and completely converted to etoposide in plasma, leading to topoisomerase-II interaction.
U.S. Food and Drug Administration–Approved Indications
Refractory testicular cancer; SCLC, first-line therapy in combination with other agents.
U.S. Food and Drug Administration–Approved Dosage
Dose Modification Criteria
Renal impairment: dose to be modified.
Adverse Reactions
DERM: alopecia, rash, urticaria, and pruritus; GI: N/V L2, mucositis, and anorexia; HEMAT: myelosuppression; INFUS: hypotension (infusion-rate related) and anaphylactic-like reactions (characterized by chills, fever, tachycardia, bronchospasm, dyspnea, and/or hypotension); OTHER: secondary malignancies.
Comments
Etoposide phosphate is a water-soluble ester of etoposide. The water solubility of etoposide phosphate lessens the potential for precipitation following dilution and during intravenous administration. Enhanced water solubility also allows for lower dilution volumes and more rapid intravenous administration compared to conventional etoposide.
EXEMESTANE (AROMISAN)
Mechanism of Action
Exemestane is an irreversible steroidal aromatase inactivator.
U.S. Food and Drug Administration–Approved Indications
Advanced breast cancer after tamoxifen failure in postmenopausal women.
U.S. Food and Drug Administration–Approved Dosage
25 mg PO daily after a meal.
Dose Modification Criteria
Renal impairment: no dose modification; hepatic impairment: no dose modification.
Note: Drug exposure is increased with hepatic and/or renal insufficiency. The safety of chronic dosing in these settings has not been studied. On the basis of experience with exemestane at repeated doses up to 200 mg daily that demonstrated a moderate increase in non–life-threatening adverse effects, dosage adjustment does not appear to be necessary.
Adverse Reactions
CNS: depression, insomnia, and anxiety; CV: hot flashes and edema; GI: nausea or increased appetite; HEMAT: lymphocytopenia; OTHER: tumor site pain, asthenia, fatigue, increased sweating, and fever.
FLOXURIDINE
Mechanism of Action
Floxuridine is an antimetabolite catabolized to fluorouracil.
U.S. Food and Drug Administration–Approved Indications
Palliative management of gastrointestinal adenocarcinoma metastasis to the liver when given by continuous regional intraarterial infusion in carefully selected patients who are considered incurable by surgery or other means.
U.S. Food and Drug Administration–Approved Dosage
0.1 to 0.6 mg/kg/day by continuous arterial infusion. The higher dose ranges (0.4 to 0.6 mg/kg/day) are usually employed for hepatic artery infusion because the liver metabolizes the drug, thereby reducing the potential for systemic toxicity. Therapy may be given until adverse reactions appear; when toxicities have subsided, therapy may be resumed. Patients may be maintained on therapy as long as response to floxuridine continues.
P.629
Dose Modification Criteria
Renal impairment: no dose modification; hepatic impairment: no dose modification; myelosuppression: dose to be modified; nonhematologic toxicity: dose to be modified
Adverse Reactions
CV: myocardial ischemia; DERM: alopecia, dermatitis, and rash; GI: N/VL1–2, stomatitis, diarrhea, enteritis, gastrointestinal ulceration and bleeding, and elevated LFT values; HEMAT: myelosuppression; INFUS: procedural complications of regional arterial infusion: arterial aneurysm, arterial ischemia, arterial thrombosis, embolism, fibromyositis, thrombophlebitis, hepatic necrosis, abscesses, infection at catheter site, bleeding at catheter site, catheter blocked, displaced or leaking; OTHER: fever, lethargy, malaise, and weakness.
FLUDARABINE (FLUDARA)
Mechanism of Action
Fludarabine is an antimetabolite.
U.S. Food and Drug Administration–Approved Indications
B-cell CLL (second-line after alkylating agent therapy)
U.S. Food and Drug Administration–Approved Dosage
25 mg per m2 i.v. over 30 minutes daily × 5 days, repeated every 28 days.
Dose Modification Criteria
Renal impairment: dose to be modified
Adverse Reactions
CNS: weakness, agitation, confusion, visual disturbances, coma (severe neurotoxicity generally seen with high-dose regimens but have been reported rarely at recommended doses), and peripheral neuropathy; CV: edema; DERM: rash; GI: N/V L1, diarrhea, and anorexia; HEMAT: myelosuppression, autoimmune hemolytic anemia, and lymphopenia; PULM: pneumonitis and cases of severe pulmonary toxicity have been reported; OTHER: myalgia, tumor lysis syndrome, and fatigue.
Comments
P.630
FLUOROURACIL (ADRUCIL AND OTHERS)
Mechanism of Action
Fluorouracil is an antimetabolite.
U.S. Food and Drug Administration–Approved Indications
Palliative management of cancer of colon, rectum, breast, stomach, and pancreas.
U.S. Food and Drug Administration–Approved Dosage
Current literature may be consulted.
Adverse Reactions
CNS: Acute cerebellar syndrome, nystagmus, headache, visual changes, and photophobia; CV: angina and ischemia; DERM: dry skin, photosensitivity, hand-foot syndrome (palmar–plantar erythrodysesthesia), alopecia, dermatitis, and thrombophlebitis; GI: N/V L2, mucositis, diarrhea, anorexia, and gastrointestinal ulceration and bleeding; HEMAT: myelosuppression; OTHER: anaphylaxis and generalized allergic reactions.
Comments
Fluorouracil may be given by continuous intravenous infusion or by rapid i.v. administration (i.v. bolus or push). The method of administration will change the toxicity profile of fluorouracil (e.g., greater potential for GI toxicities such as mucositis and diarrhea with continuous i.v. infusions and more hematologic toxicity with bolus administration).
FLUTAMIDE (EULEXIN)
Mechanism of Action
Flutamide is an antiandrogen.
U.S. Food and Drug Administration–Approved Indications
Stage D2 metastatic prostate carcinoma [in combination with luteinizing hormone releasing hormone (LHRH) agonists] or locally confined stage B2–C prostate carcinoma (in combination with LHRH agonists and radiation therapy).
U.S. Food and Drug Administration–Approved Dosage
Adverse Reactions
DERM: Rash; GI: nausea, diarrhea, constipation, increased LFT values (LFT results to be monitored periodically because of rare associations with cholestatic jaundice, hepatic necrosis, and encephalopathy); GU: impotence; ENDO: loss of libido, hot flashes, and gynecomastia.
Comments
Interacts with warfarin; international normalized ratio (INR) to be monitored closely.
P.631
FULVESTRANT (FASLODEX)
Mechanism of Action
Fulvestrant is an ER antagonist.
U.S. Food and Drug Administration–Approved Indications
Breast cancer: second-line therapy for hormone-receptor–positive metastatic breast cancer in postmenopausal women with disease progression following antiestrogen therapy.
U.S. Food and Drug Administration–Approved Dosage
250 mg i.m. injection × one dose and repeated at 1-month intervals.
Dose Modification Criteria
Renal impairment: no dosage modification; hepatic (mild impairment): no dosage modification; hepatic (moderate-to-severe impairment): no data available, to be used with caution.
Adverse Reactions
CNS: headache; CV: peripheral edema; ENDO: hot flashes; GI: nausea, constipation, diarrhea, abdominal pain, and anorexia; OTHER: pain, pharyngitis, injection-site reactions, and asthenia.
GEFITINIB (IRESSA)
Mechanism of Action
Gefitinib is an inhibitor of multiple tyrosine kinases, including those associated with the EGFR.
U.S. Food and Drug Administration–Approved Indications
NSCLC: second-line monotherapy for the treatment of patients with locally advanced or metastatic NSCLC after failure of both platinum-based and docetaxel chemotherapies.
U.S. Food and Drug Administration–Approved Dosage
250 mg PO daily
Dose Modification Criteria
Renal impairment: no dose modification; hepatic impairment: no dose modification.
Adverse Reactions
DERM: rash, acne, dry skin, and pruritus; GI: nausea, diarrhea, anorexia, and elevated LFT values; OCULAR: eye pain, corneal erosion or ulcer (sometimes in association with aberrant eyelash growth); PULM: interstitial lung disease (interstitial pneumonia, pneumonitis, and alveolitis); OTHER: asthenia, and weight loss.
Comments
P.632
GEMCITABINE (GEMZAR)
Mechanism of Action
Gemcitabine is an antimetabolite.
U.S. Food and Drug Administration–Approved Indications
U.S. Food and Drug Administration–Approved Dosage
Dose Modification Criteria
Renal impairment: dose to be used with caution; hepatic impairment: dose to be used with caution; myelosuppression: dose to be modified; nonhematologic toxicity: dose to be modified.
Adverse Reactions
DERM: rash and alopecia; GI: N/V L2, constipation, diarrhea, mucositis, increased LFT values and bilirubin, and rare reports of severe hepatotoxicity; GU: proteinuria, hematuria, and hemolytic-uremic syndrome; HEMAT: myelosuppression; PULM: dyspnea, rare reports of severe pulmonary toxicity (pneumonitis, pulmonary fibrosis, pulmonary edema, and acute respiratory distress syndrome); OTHER: fever, pain, and rare reports of vascular toxicity (vasculitis).
P.633
Comments
GEMTUZUMAB OZOGAMICIN (MYLOTARG)
Mechanism of Action
Gemtuzumab is a humanized monoclonal antibody directed at the CD33 cell surface antigen conjugated with a cytotoxic antitumor antibiotic, calicheamicin. Binding of the anti-CD33 antibody portion of gemtuzumab ozogamicin results in the internalization and release of the calicheamicin, which subsequently causes DNA double strand breakage and cell death.
U.S. Food and Drug Administration–Approved Indications
AML: second-line therapy for patients with CD33-positive AML who are in first relapse, who are 60 years of age or older, and who are not considered candidates for other cytotoxic chemotherapy.
U.S. Food and Drug Administration–Approved Dosage
Dose Modification Criteria
Renal impairment: no data available for determining dosage; hepatic impairment: no data available for determining dosage (use with caution)
Adverse Reactions
CNS: headache; CV: hypotension, hypertension; DERM: rash; GI: N/V L3, mucositis, anorexia, constipation, diarrhea, elevated LFT values and/or bilirubin level, hepatic VOD; HEMAT: myelosuppression; INFUS: fever, chills, nausea, vomiting, headache, hypotension, hypertension, hyperglycemia, hypoxia, dyspnea, and anaphylaxis; PULM: dyspnea, pulmonary infiltrates, pleural effusions, noncardiogenic pulmonary edema, pulmonary insufficiency and hypoxia, and acute respiratory distress syndrome; OTHER: tumor lysis syndrome, infection, bleeding episodes, and asthenia.
Comments
P.634
gemtuzumab ozogamicin may be at increased risk. Monitor for rapid weight gain, right upper quadrant pain, hepatomegaly, ascites, and elevations in bilirubin and/or liver enzymes.
GOSERELIN ACETATE IMPLANT (ZOLADEX)
Mechanism of Action
Goserelin is an LHRH agonist; chronic administration leads to sustained suppression of pituitary gonadotropins and subsequent suppression of serum testosterone in men and serum estradiol in women.
U.S. Food and Drug Administration–Approved Indications
U.S. Food and Drug Administration–Approved Dosage
Dose Modification Criteria
Renal impairment: no dosage modification; hepatic impairment: no dosage modification.
Adverse Reactions
CV: transient changes in blood pressure (hypo- or hypertension); CNS: pain; ENDO: (men) hot flashes, gynecomastia, sexual dysfunction, and decreased erections; (women) hot flashes, headache, vaginal dryness, vaginitis, emotional lability, change in libido, depression, increased sweating, and change in breast size; GU: erectile dysfunction and lower urinary tract symptoms; OTHER: tumor flare in the first few weeks of therapy, loss of bone mineral density, osteoporosis, bone fracture, and asthenia.
Comments
Use with caution in patients at risk for developing ureteral obstruction or spinal cord compression.
HYDROXYUREA (HYDREA, DROXIA)
Mechanism of Action
Hydroxyurea inhibits DNA synthesis; it is a radiation sensitizer.
P.635
U.S. Food and Drug Administration–Approved Indications
Use in combination with radiation therapy for melanoma; recurrent, metastatic, or inoperable ovarian cancer; resistant CML; and primary squamous cell carcinomas of the head and neck (excluding the lip). Hydroxyurea is also indicated in adult patients with sickle cell anemia with recurrent moderate-to-severe painful crises.
U.S. Food and Drug Administration–Approved Dosage
Dose Modification Criteria
Renal impairment: dose to be used with caution; hepatic impairment: dose to be used with caution; myelosuppression: dose to be modified.
P.636
Adverse Reactions
CNS: drowsiness (large doses); DERM: rash, peripheral and facial erythema, skin ulceration, dermatomyositis-like skin changes, hyperpigmentation; GI: N/V L1, diarrhea, anorexia, mucositis, and constipation; HEMAT: myelosuppression (leukopenia and anemia more severe than thrombocytopenia).
Comments
IDARUBICIN (IDAMYCIN)
Mechanism of Action
Idarubicin is an intercalating agent and a topoisomerase-II inhibitor.
U.S. Food and Drug Administration–Approved Indications
In combination with other agents for adult AML (FAB classification M1 to M7).
U.S. Food and Drug Administration–Approved Dosage
AML induction in combination with cytarabine: 12 mg per m2 slow i.v. injection (over 10 to 15 minutes) daily for 3 days.
Dose Modification Criteria
Renal impairment: dose to be modified; hepatic impairment: dose to be modified; mucositis: dose to be modified.
Adverse Reactions
CV: CHF, arrhythmia; DERM: alopecia, radiation recall, and rash; GI: N/V L3, mucositis, abdominal cramps, and diarrhea; HEMAT: myelosuppression.
Comments
IFOSFAMIDE (IFEX)
Mechanism of Action
Ifosfamide is an alkylating agent.
U.S. Food and Drug Administration–Approved Indications
Germ cell testicular cancer (third-line therapy in combination with other agents).
U.S. Food and Drug Administration–Approved Dosage
1.2 g per m2 i.v. daily for 5 days, repeated every 3 weeks. Give Mesna 20% (wt/wt; 240 mg per m2 per dose for a 1.2 g per m2 ifosfamide dose) at time of ifosfamide, and then 4 and 8 hours after ifosfamide.
Dose Modification Criteria
Renal impairment: no known experience with dosage; hepatic impairment: no known experience with dosage; myelosuppression: dose to be modified; neurotoxicity: dose to be modified.
Adverse Reactions
CNS: encephalopathy, somnolence, confusion, depressive psychosis, hallucinations, and dizziness; DERM: alopecia; GI: N/V L3, increased LFT values; GU: hemorrhagic cystitis, Fanconi syndrome (proximal tubular impairment), glomerular or tubular toxicity; HEMAT: myelosuppression.
Comments
IMATINIB (GLEEVEC)
Mechanism of Action
Imatinib is an inhibitor of multiple tyrosine kinases, including the Bcr-Abl tyrosine kinase, which is created by the Philadelphia chromosome abnormality in CML. Imatinib is also an inhibitor of the receptor tyrosine kinases for platelet-derived growth factor (PDGF) and stem cell factor (SCF), c-kit, and inhibits PDGF- and SCF-mediated cellular events.
P.637
U.S. Food and Drug Administration–Approved Indications
U.S. Food and Drug Administration–Approved Dosage
Dose Modification Criteria
Renal impairment: no data available; hepatic impairment: no data available; myelosuppression: dose to be modified; nonhematologic toxicity: dose to be modified
Adverse Reactions
CNS: headache and dizziness; CV: superficial edema (periorbital, lower limb), severe fluid retention (pleural effusion, ascites, pulmonary edema, and rapid weight gain); DERM: rash GI: nausea, diarrhea, GI irritation, dyspepsia, elevated LFT values, and severe hepatotoxicity; HEMAT: myelosuppression, and hemorrhage; PULM: cough; OTHER: muscle cramps, pain (musculoskeletal, joint, and abdominal), myalgia, arthralgia, nasopharyngitis, fatigue, and fever.
Comments
P.638
INTERFERON α-2A (ROFERON-A)
Mechanism of Action
Interferon α-2A suppresses cell proliferation and enhances macrophage phagocytic activity and lymphocyte cytotoxicity.
P.639
U.S. Food and Drug Administration–Approved Indications
Oncology indications (adults, as old as 18 years or older): Hairy cell leukemia, AIDS-related Kaposi sarcoma, and CML (Philadelphia chromosome positive).
Other indications: chronic hepatitis C
U.S. Food and Drug Administration–Approved Dosage
Dose Modification Criteria
In cases of serious adverse events: dose is to be modified.
Adverse Reactions
CNS: dizziness, depression, suicidal ideation, and paresthesias; DERM: skin rash, alopecia; ENDO: thyroid abnormalities; GI: diarrhea, nausea, anorexia, taste alteration, abdominal pain, and increased LFT values; HEMAT: myelosuppression; PULM: dyspnea, pulmonary infiltrates, pneumonitis, and pneumonia; OTHER: flu-like symptoms (i.e., fever, chills, headache, fatigue, malaise, and myalgia), hypersensitivity reactions, ophthalmologic disorders, and autoimmune disorders.
Comments
INTERFERON α-2B (INTRON A)
Mechanism of Action
Interferon α-2B suppresses cell-proliferation and enhances macrophage phagocytic activity and lymphocyte cytotoxicity.
U.S. Food and Drug Administration–Approved Indications
Oncology indications (adults, as old as 18 years or older): hairy cell leukemia, malignant melanoma (adjuvant therapy to surgical treatment), AIDS-related Kaposi sarcoma, and follicular lymphoma (clinically aggressive disease in conjunction with anthracycline-containing combination chemotherapy).
Other indications: condyloma acuminata, chronic hepatitis C, and chronic hepatitis B
U.S. Food and Drug Administration–Approved Dosage
Dose Modification Criteria
In case of serious adverse events: dose is to be modified.
Adverse Reactions
CNS: dizziness, depression, suicidal ideation, and paresthesias; DERM: skin rash, alopecia; ENDO: thyroid abnormalities; GI: diarrhea, nausea, anorexia, taste alteration, abdominal pain, and increased LFT values; HEMAT: myelosuppression; PULM: dyspnea, pulmonary infiltrates, pneumonitis, and pneumonia; OTHER: “flu-like symptoms” (fever, chills, headache, fatigue, malaise, and myalgia), hypersensitivity reactions, ophthalmologic disorders, and autoimmune disorders.
Comments
IRINOTECAN (CAMPTOSAR)
Mechanism of Action
Irinotecan is a topoisomerase-I inhibitor.
U.S. Food and Drug Administration–Approved Indications
U.S. Food and Drug Administration–Approved Dosage
P.640
Dose Modification Criteria
Hepatic impairment: dose to be modified; pelvic or abdominal irradiation: dose to be modified; myelosuppression: dose to be modified; nonhematologic toxicity: dose to be modified (package labeling to be consulted for dose modifications).
P.641
Adverse Reactions
CNS: insomnia and dizziness; CV: vasodilation; DERM: alopecia, sweating, and rash; GI: N/V L3, diarrhea (early and late), abdominal pain, mucositis, anorexia, flatulence, and increased bilirubin, LFT values; HEMAT: myelosuppression; PULM: dyspnea, coughing, and rhinitis; OTHER: asthenia and fevers.
Comments
Can induce both early (within 24 hours of administration) and late forms of diarrhea. The early onset diarrhea is cholinergic in nature and may be accompanied by symptoms of rhinitis, increased salivation, miosis, lacrimation, diaphoresis, flushing, and abdominal cramping. These early cholinergic symptoms can be treated by administration of atropine. Late onset of diarrhea (generally after 24 hours) should be treated aggressively with high-dose loperamide. Each patient should be instructed to have loperamide readily available so that treatment can be initiated at the earliest onset of diarrhea. Package labeling may be consulted for dosage recommendations for atropine and loperamide.
LETROZOLE (FEMARA)
Mechanism of Action
Letrozole is a selective, nonsteroidal aromatase inhibitor.
U.S. Food and Drug Administration–Approved Indications
Breast cancer:
U.S. Food and Drug Administration–Approved Dosage
2.5 mg PO daily.
Dose Modification Criteria
Renal impairment (CrCl ≥10 mL per minute): no dose modification; hepatic (mild-to-moderate impairment): no dose modification; hepatic (severe impairment): dose to be modified.
Adverse Reactions
CNS: headache; GI: nausea, constipation, or diarrhea; OTHER: hot flashes, fatigue, musculoskeletal pain, arthralgia, and peripheral edema.
LEUPROLIDE ACETATE (LUPRON, LUPRON DEPOT, LUPRON DEPOT-3 MONTH, LUPRON DEPOT-4 MONTH, VIADUR)
Mechanism of Action
Leuprolide acetate is an LHRH agonist; chronic administration leads to sustained suppression of pituitary gonadotropins and subsequent suppression of serum testosterone in men and serum estradiol in women.
U.S. Food and Drug Administration–Approved Indications
U.S. Food and Drug Administration–Approved Dosage
Prostate cancer: Lupron: 1 mg s.c. daily; Lupron Depot: 7.5 mg i.m. monthly; Lupron Depot-3 month: 22.5 mg i.m. every 3 months; Lupron Depot-4 month: 30 mg i.m. every 4 months; Viadur implant: one implant (contains 72 mg of leuprolide acetate) every 12 months.
Adverse Reactions
CV: transient changes in blood pressure (hypo- or hypertension); ENDO: hot flashes, gynecomastia, sexual dysfunction, and decreased erections; GU: erectile dysfunction, lower urinary tract symptoms, and testicular atrophy; OTHER: tumor flare in the first few weeks of therapy, bone pain, injection-site reactions, loss of bone mineral density, osteoporosis, bone fracture, and asthenia.
Comments
LEVAMISOLE (ERGAMISOL)
Mechanism of Action
Mechanism of levamisole is unknown; levamisole may be an immunomodulator.
U.S. Food and Drug Administration–Approved Indications
Adjuvant treatment in combination with fluorouracil after surgical resection in patients with Dukes stage C colon cancer
U.S. Food and Drug Administration–Approved Dosage
P.642
Dose Modification Criteria
Hepatic (severe impairment): use with caution; myelosuppression: dose to be modified.
Adverse Reactions
CNS: cases of an encephalopathy syndrome associated with demyelination reported; DERM: rash, dermatitis, and alopecia; GI: nausea, diarrhea, mucositis, anorexia, and abdominal pain; HEMAT: myelosuppression and agranulocytosis; OTHER: dysgeusia and fatigue.
Comments
Monitor for myelosuppression and agranulocytosis. Concomitant use with alcohol may result in a disulfiram (Antabuse) reaction. Levamisole may interact with phenytoin, leading to elevated phenytoin plasma levels; monitor phenytoin plasma levels with concomitant use. Levamisole may also interact with warfarin, leading to an increased PT and INR.
LOMUSTINE (CCNU, CEE NU)
Mechanism of Action
Lomustine is an alkylating agent.
U.S. Food and Drug Administration–Approved Indications
Primary and metastatic brain tumors; Hodgkin disease (second-line therapy in combination with other agents).
U.S. Food and Drug Administration–Approved Dosage
Single-agent therapy: 100 to 130 mg per m2 as a single oral dose every 6 weeks.
Dose Modification Criteria
Myelosuppression: dose to be modified.
Adverse Reactions
GI: N/V (≥60 mg per m2: L5, ≤60 mg per m2: L3) increased LFT values, and mucositis; GU: increased BUN and Cr; HEMAT: severe delayed myelosuppression and cumulative myelosuppression; PULM: (cumulative and usually occurs after 6 months of therapy or a cumulative lifetime dose of 1,100 mg per m2, although it has been reported with total lifetime doses as low as 600 mg), fibrosis, and infiltrate; OTHER: secondary malignancies.
Comments
P.643
MECHLORETHAMINE (MUSTARGEN)
Mechanism of Action
Mechlorethamine is an alkylating agent.
U.S. Food and Drug Administration–Approved Indications
U.S. Food and Drug Administration–Approved Dosage
Dose Modification Criteria
Myelosuppression: dose to be modified.
Adverse Reactions
CNS: vertigo, tinnitus, and diminished hearing; DERM: alopecia, phlebitis, tissue damage or necrosis with extravasation, rash; GI: N/V L5, metallic taste in mouth, and diarrhea; HEMAT: myelosuppression; OTHER: hyperuricemia, secondary malignancies, infertility, and azoospermia.
Comments
Vesicant.
MEDROXYPROGESTERONE ACETATE (DEPO-PROVERA)
Mechanism of Action
Medroxyprogesterone acetate is a derivative of progesterone.
U.S. Food and Drug Administration–Approved Indications
Adjunctive therapy and palliative treatment of inoperable, recurrent, and metastatic endometrial or renal cancer.
U.S. Food and Drug Administration–Approved Dosage
400 to 1,000 mg i.m. injection × one dose. Doses may be repeated weekly initially; if improvement is noted, the dose may be reduced to maintenance doses as low as 400 mg i.m. monthly.
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Adverse Reactions
CNS: headache, nervousness, dizziness, and depression; CV: edema, weight gain, and thromboembolic events; DERM: urticaria, pruritus, rash, acne, alopecia, and hirsutism; ENDO: breast tenderness and galactorrhea; GI: nausea, cholestatic jaundice; GU: breakthrough bleeding, spotting, change in menstrual flow, amenorrhea, and changes in cervical erosion and secretions; OCULAR: neuroocular lesions (retinal thrombosis and optic neuritis); OTHER: hypersensitivity reactions, fever, fatigue, insomnia, somnolence, and injection-site reactions.
MEGESTROL (MEGACE AND OTHERS)
Mechanism of Action
Megestrol is a progestational agent.
U.S. Food and Drug Administration–Approved Indications
Palliative therapy of advanced breast cancer and endometrial cancer.
U.S. Food and Drug Administration–Approved Dosage
Adverse Reactions
CNS: mood changes; CV: deep vein thrombosis; DERM: alopecia; ENDO: Cushing-like syndrome, hyperglycemia, glucose intolerance, weight gain, and hot flashes; GU: vaginal bleeding; OTHER: carpal tunnel syndrome and tumor flare.
Comments
Other indications include cancer and AIDS-related anorexia and cachexia as an appetite stimulant and to promote weight gain. Usual dose range: 160 to 800 mg per day (consult current literature).
MELPHALAN (ALKERAN); MELPHALAN INJECTION
Mechanism of Action
Melphalan is an alkylating agent.
U.S. Food and Drug Administration–Approved Indications
Palliative therapy for multiple myeloma and nonresectable ovarian cancer.
U.S. Food and Drug Administration–Approved Dosage
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repeat administration at 4-week intervals. Current literature to be referred to for other dosing regimens.
Dose Modification Criteria
Renal impairment: dose to be modified; myelosuppression: dose to be modified.
Adverse Reactions
DERM: vasculitis, alopecia, and skin ulceration or necrosis at injection site (rare); HEMAT: myelosuppression and hemolytic anemia; GI: N/V L1 (oral), L4 (high dose i.v.), diarrhea, mucositis, anorexia, and increased LFT values; PULM: pulmonary toxicity (pulmonary fibrosis and interstitial pneumonitis); OTHER: hypersensitivity reactions, secondary malignancies, and infertility.
Comments
MERCAPTOPURINE (PURINETHOL)
Mechanism of Action
Mercaptopurine is an antimetabolite.
U.S. Food and Drug Administration–Approved Indications
U.S. Food and Drug Administration–Approved Dosage
Dose Modification Criteria
Renal impairment: dose reduction to be considered for modification; hepatic impairment: dose reduction to be considered for modification; myelosuppression: dose to be modified.
Adverse Reactions
DERM: rash and alopecia; GI: anorexia, N/V L1, mucositis, and hepatotoxicity; HEMAT: myelosuppression; OTHER: tumor lysis syndrome.
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Comments
METHOTREXATE
Mechanism of Action
Methotrexate is an antimetabolite.
U.S. Food and Drug Administration–Approved Indications
U.S. Food and Drug Administration–Approved Dosage
Dose Modification Criteria
Renal impairment: dose to be modified.
Adverse Reactions
CNS: acute chemical arachnoiditis (intrathecal), subacute myelopathy (intrathecal), chronic leukoencephalopathy (intrathecal), and acute neurotoxicity or encephalopathy (high-dose i.v. therapy); DERM: alopecia, rash, urticaria, telangiectasia, acne, photosensitivity, and severe
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dermatologic reactions; GI: N/V (≤50 mg per m2 L1, >50 to <250 mg per m2 L2, 250 to 1,000 mg per m2 L3, >1,000 mg per m2 L4), mucositis/stomatitis, diarrhea, increased LFT values, and acute and chronic hepatotoxicity; GU: renal failure (high-dose therapy) and cystitis; HEMAT: myelosuppression; PULM: interstitial pneumonitis; OTHER: fever, malaise, chills, fatigue, teratogenic, and tumor lysis syndrome.
Comments
MITOMYCIN C (MUTAMYCIN)
Mechanism of Action
Mitomycin C induces DNA cross-links through alkylation; inhibits DNA and RNA synthesis.
U.S. Food and Drug Administration–Approved Indications
Disseminated gastric cancer or pancreatic cancer (in combination with other agents and as palliative treatment when other modalities have failed).
U.S. Food and Drug Administration–Approved Dosage
Single-agent therapy: 20 mg per m2 i.v. × 1 dose repeated every 6 to 8 weeks.
Current literature may be referred to for alternative dosing regimens and combination regimens.
Dose Modification Criteria
Adverse Reactions
CV: CHF (patients with prior doxorubicin exposure); DERM: alopecia, pruritus, tissue damage or necrosis with extravasation; GI: anorexia, N/V L2, mucositis, and diarrhea; GU: increased Cr; HEMAT: myelosuppression (may be cumulative); PULM: nonproductive cough, dyspnea, and interstitial pneumonia; OTHER: fever, hemolytic uremic syndrome, malaise, and weakness.
Comments
Vesicant.
MITOTANE (LYSODREN)
Mechanism of Action
Mitotane is an adrenal cytotoxic agent.
P.648
U.S. Food and Drug Administration–Approved Indications
Inoperable, functional, and nonfunctional adrenal cortical carcinoma.
U.S. Food and Drug Administration–Approved Dosage
Initial dose: 2 to 6 g PO per day in three to four divided doses. Doses are usually increased incrementally to 9 to 10 g per day or until maximum tolerated dose is achieved. Maximum tolerated dose range varies from 2 to 16 g per day but has usually been 9 to 10 g per day. Total daily doses should be administered in three to four divided doses.
Adverse Reactions
CNS: vertigo, depression, lethargy, somnolence, and dizziness; DERM: transient skin rashes; GI: anorexia, nausea, and diarrhea; OTHER: adrenal insufficiency.
Comments
MITOXANTRONE (NOVANTRONE)
Mechanism of Action
Mitoxantrone interacts with DNA and is an intercalating agent and a topoisomerase-II inhibitor.
U.S. Food and Drug Administration–Approved Indications
U.S. Food and Drug Administration–Approved Dosage
Dose Modification Criteria
Renal impairment: no data available; hepatic impairment: to be used with caution; dose adjustment may be considered.
Adverse Reactions
CV: CHF (clinical risk increases after a lifetime cumulative dose of 140 mg per m2), tachycardia, electrocardiographic changes, and chest pain; DERM: rash, alopecia, urticaria, nail bed changes; GI: N/V (>15 mg per m2: L4, ≤15 mg per m2: L3), mucositis, constipation,
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anorexia, and increased LFT values; HEMAT: myelosuppression; PULM: dyspnea; OTHER: bluish green urine, sclera may turn bluish, phlebitis (irritant), fatigue, secondary leukemias, and tumor lysis syndrome.
Comments
NILUTAMIDE (NILANDRON)
Mechanism of Action
Nilutamide is an antiandrogen.
U.S. Food and Drug Administration–Approved Indications
Metastatic prostate cancer (stage D2; in combination therapy with surgical castration). Dosing should begin on same day or day after surgical castration.
U.S. Food and Drug Administration–Approved Dosage
Give 300 mg PO daily × 30 days, and then 150 mg PO daily (with or without food).
Adverse Reactions
CNS: dizziness; CV: hypertension, and angina; ENDO: hot flashes, impotence, and decreased libido; GI: nausea, anorexia, increased LFT values (LFT results to be monitored periodically because of rare associations with cholestatic jaundice, hepatic necrosis, and encephalopathy), and constipation; OCULAR: visual disturbances and impaired adaptation to dark; PULM: interstitial pneumonitis and dyspnea.
Comments
OXALIPLATIN (ELOXATIN)
Mechanism of Action
Oxaliplatin is an alkylating-like agent producing interstrand DNA cross-links.
U.S. Food and Drug Administration–Approved Indications
Advanced or metastatic colorectal cancer:
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U.S. Food and Drug Administration–Approved Dosage
Combined therapy with infusional fluorouracil and leucovorin (FOLFOX regimen)
Day 1:
Day 2:
Cycles are repeated every 2 weeks.
Dose Modification Criteria
Renal impairment: no data available (to be used with caution); myelosuppression: dose to be modified; nonhematologic toxicity: dose to be modified.
Adverse Reactions
CNS: peripheral sensory neuropathies (details follow under “Comments”), headache; CV: edema, thromboembolic events; DERM: injection-site reactions; GI: N/V L3, diarrhea, mucositis or stomatitis, abdominal pain, anorexia, taste perversion, and elevated LFT values; GU: elevated serum creatinine; HEMAT: myelosuppression; PULM: pulmonary fibrosis, dyspnea, and cough; OTHER: fatigue, fever, back pain, pain, and hypersensitivity reaction.
Comments
PACLITAXEL (TAXOL)
Mechanism of Action
Paclitaxel stabilizes microtubule assembly.
U.S. Food and Drug Administration–Approved Indications
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U.S. Food and Drug Administration–Approved Dosage
Dose Modification Criteria
Hepatic impairment: dose to be modified; myelosuppression: dose to be modified; nonhematologic toxicity (neuropathy): dose to be modified.
Adverse Reactions
CNS: peripheral neurosensory toxicity (paresthesia, dysesthesia, and pain); CV: hypotension, bradycardia, and electrocardiographic changes; DERM: alopecia, onycholysis (more common with weekly dosing), and injection-site reactions; GI: N/V L2, diarrhea, and mucositis; HEMAT: myelosuppression; INFUS: acute hypersensitivity-type reactions; OTHER: arthralgia, and myalgia.
Comments
PEGASPARGASE (ONCASPAR)
Mechanism of Action
Pegaspargase is a modified (pegylated) version of the enzyme L-asparaginase. L-asparaginase depletes asparagine, an amino acid required by some leukemic cells.
P.652
U.S. Food and Drug Administration–Approved Indications
Patients with ALL who are hypersensitive to native forms of L-asparaginase.
U.S. Food and Drug Administration–Approved Dosage
Adverse Reactions
CNS: malaise, confusion, lethargy, and depression; CV: chest pain, hypertension, and hypotension; DERM: alopecia, itching, and injection-site reactions; ENDO: hyperglycemia; GI: anorexia; N/V L1-2, hepatotoxicity, increased LFT values, and pancreatitis; GU: increased BUN and Cr; HEMAT: hypofibrinogenemia; PULM: respiratory distress, cough, and epistaxis; OTHER: hypersensitivity reaction, fever, arthralgia, musculoskeletal pain, and tumor lysis syndrome.
Comments
Contraindications: active pancreatitis or history of pancreatitis, serious hemorrhagic episode with native L-asparaginase, serious allergic reactions (e.g., bronchospasm) to native L-asparaginase.
PEMETREXED (ALIMTA)
Mechanism of Action
Pemetrexed is an antimetabolite and also an antifolate that disrupts folate-dependent metabolic process essential for cell replication.
U.S. Food and Drug Administration–Approved Indications
Malignant pleural mesothelioma: in combination with cisplatin in patients whose disease is unresectable or who are otherwise ineligible for curative surgery.
U.S. Food and Drug Administration–Approved Dosage
Malignant pleural mesothelioma: 500 mg per m2 i.v. over 10 minutes on day 1 of each 21-day cycle. The recommended dose of cisplatin (in combination with pemetrexed) is 75 mg per m2 i.v. over 2 hours, beginning approximately 30 minutes after the end of pemetrexed. See comments section for premedication regimen for pemetrexed.
Dose Modification Criteria
Renal impairment (CrCl ≥45 mL per minute): no dose modification, renal impairment (CrCl <45 mL per minute): administration is not recommended; hepatic impairment: no data available; myelosuppression: dose to be modified; nonhematologic toxicity: dose to be modified.
Adverse Reactions
DERM: rash, desquamation; GI: N/V L2, mucositis, pharyngitis, diarrhea, anorexia, and increased LFT values; HEMAT: neutropenia, thrombocytopenia, and anemia; OTHER: fatigue, fever.
P.653
Comments
PENTOSTATIN (NIPENT)
Mechanism of Action
Pentostatin is an antimetabolite and an adenosine deaminase inhibitor.
U.S. Food and Drug Administration–Approved Indications
Hairy cell leukemia (first-line and in α-interferon-refractory disease)
U.S. Food and Drug Administration–Approved Dosage
4 mg per m2 i.v. every other week. The optimal treatment duration has not been determined. The package insert suggests continued treatment until a complete response has been achieved followed by two additional doses.
Dose Modification Criteria
Renal impairment: dose to be modified; myelosuppression: dose to be modified.
Adverse Reactions
DERM: rash; GI: N/V L3-4, and elevated LFT values; GU: mild transient rise in serum creatinine; HEMAT: leukopenia, anemia, and thrombocytopenia; OTHER: fever, infection, and fatigue.
Comments
POLIFEPROSAN 20 WITH CARMUSTINE IMPLANT (GLIADEL WAFER)
Mechanism of Action
The polifeprosan 20 with carmustine implant is designed to deliver carmustine directly into the surgical cavity created when a brain tumor is resected. On exposure to the aqueous environment
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of the resection cavity, carmustine is released from the copolymer and diffuses into the surrounding brain tissue. Carmustine is an alkylating agent.
U.S. Food and Drug Administration–Approved Indications
U.S. Food and Drug Administration–Approved Dosage
Each wafer contains 7.7 mg of carmustine. Up to eight wafers should be implanted at time of surgery (eight wafers result in a dose of 61.6 mg).
Adverse Reactions
CNS: meningitis, abscess, and brain edema; GI: nausea; OTHER: abnormal healing, pain, and fever.
Comments
Wafers can be broken in half. Proper handling and disposal precautions should be observed.
PORFIMER (PHOTOFRIN)
Mechanism of Action
Porfimer is a photosensitizing agent.
U.S. Food and Drug Administration–Approved Indications
U.S. Food and Drug Administration–Approved Dosage
2 mg per kg i.v. injection over 3 to 5 minutes × one dose followed by photodynamic therapy. For the treatment of esophageal and endobronchial cancer, patients may receive up to three additional courses; each course should be administered no sooner than 30 days after the previous course. For the ablation of high-grade dysplasia in Barrett esophagus, patients may receive up to three additional courses; each course should be administered no sooner than 90 days after the previous course.
Adverse Reactions
CNS: anxiety, confusion, and insomnia; CV: hypertension, hypotension, heart failure, chest pain, atrial fibrillation, and tachycardia; DERM: photosensitivity; HEMAT: anemia; GI: N/VL2, abdominal pain, anorexia, constipation, dysphagia, esophageal edema, and esophageal stricture;
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PULM: pleural effusion, dyspnea, pneumonia, pharyngitis, cough, respiratory insufficiency, and tracheoesophageal fistula; OTHER: fever.
Comments
Patients are photosensitive (including eyes) for at least 30 days after administration.
PROCARBAZINE (MATULANE)
Mechanism of Action
Mechanism of action of procarbazine is unknown. There is evidence that the drug may act by inhibition of protein, RNA, and DNA synthesis.
U.S. Food and Drug Administration–Approved Indications
Stages III and IV Hodgkin disease: first-line therapy in combination with other anticancer drugs. [Procarbazine is used as part of the MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) chemotherapy regimen.]
U.S. Food and Drug Administration–Approved Dosage
Adverse Reactions
CNS: paresthesias, confusion, lethargy, and mental depression; DERM: pruritus, hyperpigmentation, and alopecia; GI: anorexia, N/V L4, stomatitis, xerostomia, diarrhea, and constipation; HEMAT: myelosuppression; OTHER: fever, and myalgia.
Comments
RITUXIMAB (RITUXAN)
Mechanism of Action
Rituximab is a chimeric (murine, human) monoclonal antibody directed at the CD20 antigen found on the surface of normal and malignant B lymphocytes.
U.S. Food and Drug Administration–Approved Indications
Relapsed or refractory low-grade or follicular, CD20-positive, B cell, non-Hodgkin lymphoma.
P.656
U.S. Food and Drug Administration–Approved Dosage
Adverse Reactions
CNS: headache, and dizziness; CV: hypotension, arrhythmias, and peripheral edema; DERM: rash, pruritus, urticaria, and severe mucocutaneous reactions; GI: N/V L1-2, and abdominal pain; HEMAT: angioedema, leukopenia, thrombocytopenia, and neutropenia; INFUS: fever, chills, rigors, hypoxia, pulmonary infiltrates, adult respiratory distress syndrome, myocardial infarction, ventricular fibrillation, or cardiogenic shock; OTHER: throat irritation, rhinitis, bronchospasm, hypersensitivity reaction, myalgia, back pain, and tumor lysis syndrome.
Comments
STREPTOZOTOCIN (ZANOSAR)
Mechanism of Action
Streptozotocin is an alkylating agent.
U.S. Food and Drug Administration–Approved Indications
Metastatic islet cell carcinoma of the pancreas (functional and nonfunctional carcinomas).
U.S. Food and Drug Administration–Approved Dosage
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therapeutic response and who have not experienced significant toxicity with the previous course of treatment. However, a single dose should not exceed 1,500 mg per m2.
Dose Modification Criteria
Renal impairment: to be used with caution, dose reduction may be considered.
Adverse Reactions
DERM: injection-site reactions (irritant); ELECTRO: hypophosphatemia; ENDO: dysglycemia, may lead to insulin-dependent diabetes; GI: N/V L5, increased LFT values, diarrhea; GU: azotemia, anuria, renal tubular acidosis, increased BUN and serum creatinine, glycosuria; HEMAT: myelosuppression.
Comments
TAMOXIFEN (NOLVADEX)
Mechanism of Action
Tamoxifen is a nonsteroidal antiestrogen.
U.S. Food and Drug Administration–Approved Indications
U.S. Food and Drug Administration–Approved Dosage
Adverse Reactions
CV: thromboembolism, stroke, and pulmonary embolism; DERM: skin rash; ENDO: hot flashes; GI: nausea, anorexia; GU: menstrual irregularities, pruritus vulvae, and vaginal discharge or bleeding; HEMAT: bone marrow depression; OCULAR: vision disturbances and
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cataracts; PULM: dyspnea, chest pain, and hemoptysis; OTHER: dizziness, headaches, tumor or bone pain, pelvic pain, and uterine malignancies.
Comments
TEMOZOLOMIDE (TEMODAR)
Mechanism of Action
Temozolomide is an alkylating agent.
U.S. Food and Drug Administration–Approved Indications
Refractory anaplastic astrocytoma: Second-line therapy in adults (after a nitrosourea and procarbazine regimen).
U.S. Food and Drug Administration–Approved Dosage
Initial dose: 150 mg per m2 PO daily × 5 consecutive days every 28 days. If the initial dose leads to acceptable hematologic parameters at the nadir and on day of dosing (criteria in package insert to be verified), the temozolomide dose may be increased to 200 mg per m2 PO daily × 5 consecutive days per 28 day treatment cycle.
Dose Modification Criteria
Renal (severe impairment): to be used with caution; hepatic (severe impairment): to be used with caution; myelosuppression: dose to be modified.
Adverse Reactions
CNS: headache; HEMAT: myelosuppression; GI: N/V L2 (reduced by taking on an empty stomach); OTHER: asthenia, fatigue.
Comments
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TENIPOSIDE (VUMON)
Mechanism of Action
Teniposide is a topoisomerase-II inhibitor.
U.S. Food and Drug Administration–Approved Indications
Refractory childhood ALL: induction therapy as a second-line therapy (in combination with other agents).
U.S. Food and Drug Administration–Approved Dosage
Dose Modification Criteria
Renal impairment: to be used with caution, no guidelines available; hepatic impairment: to be used with caution, no guidelines available.
Adverse Reactions
CV: hypotension with rapid infusion; DERM: alopecia, thrombophlebitis, and tissue damage secondary to drug extravasation; GI: diarrhea, N/V L2, and mucositis; HEMAT: myelosuppression; OTHER: anaphylaxis, and hypersensitivity.
Comments
TESTOLACTONE (TESLAC)
Mechanism of Action
Testolactone is a synthetic derivative of testosterone that appears to inhibit steroid aromatase activity and consequently cause a reduction in estrone synthesis.
U.S. Food and Drug Administration–Approved Indications
U.S. Food and Drug Administration–Approved Dosage
250 mg PO q.i.d. (4 times daily; total daily dose: 1,000 mg per day).
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Adverse Reactions
CNS: paresthesia; CV: hypertension, peripheral edema, DERM: maculopapular erythema, alopecia, and nail growth disturbance; GI: anorexia, nausea; OTHER: malaise, aches, and glossitis.
THIOGUANINE (TABLOID)
Mechanism of Action
Thioguanine is an antimetabolite.
U.S. Food and Drug Administration–Approved Indications
ANLL: remission induction, remission consolidation, and maintenance therapy
U.S. Food and Drug Administration–Approved Dosage
Adverse Reactions
GI: anorexia and stomatitis, N/V L1, increased LFT values, and increased bilirubin (cases of venoocclusive hepatic disease have been reported in patients receiving combination chemotherapy for leukemia); HEMAT: myelosuppression; OTHER: hyperuricemia and tumor lysis syndrome.
Comments
THIOTEPA (THIOPLEX)
Mechanism of Action
Thiotepa is an alkylating agent.
U.S. Food and Drug Administration–Approved Indications
Superficial papillary carcinoma of the bladder, controlling intracavitary effusions secondary to diffuse or localized neoplasms of the serosal cavities, breast cancer, ovarian cancer, Hodgkin disease, and lymphosarcoma.
U.S. Food and Drug Administration–Approved Dosage
P.661
Adverse Reactions
CNS: dizziness, headache, blurred vision, and conjunctivitis; DERM: alopecia and pain at the injection site; GI: anorexia, N/V L2, and mucositis at high doses; GU: amenorrhea, reduced spermatogenesis, dysuria, and chemical or hemorrhagic cystitis (intravesical); HEMAT: myelosuppression; OTHER: fever, hypersensitivity reactions, fatigue, weakness, and anaphylaxis.
TOPOTECAN (HYCAMTIN)
Mechanism of Action
Topotecan is a topoisomerase-I inhibitor.
U.S. Food and Drug Administration–Approved Indications
U.S. Food and Drug Administration–Approved Dosage
Ovarian or SCLC: 1.5 mg per m2 i.v. over 30 minutes daily × 5 days, starting on day 1 of a 21-day course.
Dose Modification Criteria
Renal (mild impairment, CrCl 40 to 60 mL per minute): no dose modification; renal (moderate impairment, CrCl 20 to 39 mL per minute): dose to be modified; renal (severe impairment, <20 mL per minute): no recorded experience with dosage; hepatic impairment (bilirubin, mild-to-moderate elevation): no dosage modification; myelosuppression: dose to be modified.
Adverse Reactions
CNS: headache; DERM: alopecia and injection-site reactions; HEMAT: myelosuppression; GI: N/V L2, diarrhea, constipation, abdominal pain, stomatitis, and anorexia; OTHER: fatigue and asthenia.
Comments
Concomitant filgrastim may worsen neutropenia. If used, start filgrastim at least 24 hours after last topotecan dose.
TOREMIFENE (FARNESTON)
Mechanism of Action
Toremifene is a nonsteroidal antiestrogen.
U.S. Food and Drug Administration–Approved Indications
Metastatic breast cancer in postmenopausal women with ER–positive or unknown tumors.
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U.S. Food and Drug Administration–Approved Dosage
60 mg PO daily.
Adverse Reactions
CV: thromboembolism, stroke, and pulmonary embolism; CNS: dizziness, depression; DERM: skin discoloration, dermatitis; ELECTRO: hypercalcemia; ENDO: hot flashes; GI: N/V L1, constipation and elevated LFT values; GU: vaginal discharge, vaginal bleeding; OCULAR: dry eyes, ocular changes, and cataracts; OTHER: sweating and tumor flare.
Comments
Not to be used in patients with a history of thromboembolic disease or endometrial hyperplasia.
TRASTUZUMAB (HERCEPTIN)
Mechanism of Action
Trastuzumab is a humanized monoclonal antibody directed at the human EGFR 2 protein (HER2).
U.S. Food and Drug Administration–Approved Indications
U.S. Food and Drug Administration–Approved Dosage
Initial loading dose of 4 mg per kg i.v. infused over 90 minutes. Weekly maintenance dose of 2 mg per kg i.v. infused over 30 minutes (if first dose is tolerated).
Adverse Reactions
CNS: headache and dizziness (infusion reactions to be referred); CV: cardiomyopathy, ventricular dysfunction, CHF (incidence higher in patients receiving concurrent chemotherapy), and hypotension (infusion reactions); DERM: rash; HEMAT: myelosuppression (anemia and leukopenia with concurrent chemotherapy); GI: diarrhea, nausea, vomiting, and anorexia; INFUS: (first infusion) chills, fever, nausea, vomiting, pain (at tumor sites), rigors, headache, dizziness, dyspnea, rash, hypotension, and asthenia; PULM: cough, dyspnea, rhinitis, adult respiratory distress syndrome, bronchospasm, angioedema, wheezing, pleural effusions, pulmonary infiltrates, noncardiogenic pulmonary edema, pulmonary insufficiency, and hypoxia (some severe pulmonary reactions required supplemental oxygen or ventilatory support); OTHER: infection (higher incidence of mild upper respiratory infections and catheter infections observed in one randomized trial), asthenia, allergic reactions, and anaphylaxis.
Comments
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TRETINOIN (VESANOID)
Mechanism of Action
Tretinoin induces maturation, cytodifferentiation, and decreased proliferation of Acute Promyleocytic Leukemia cells.
U.S. Food and Drug Administration–Approved Indications
APL: Induction of remission in patients with APL (FAB M3, including the M3 variant), characterized by the t(15;17) translocation and/or the presence of the PML/RARα gene, who are refractory to or relapsed after anthracycline chemotherapy or for whom anthracycline therapy is contraindicated.
U.S. Food and Drug Administration–Approved Dosage
22.5 mg per m2 PO twice daily (total daily dose: 45 mg per m2) until complete remission is documented. Therapy should be discontinued 30 days after complete remission is obtained or after 90 days of treatment, whichever comes first.
Adverse Reactions
CNS: dizziness, anxiety, insomnia, headache, depression, confusion, intracranial hypertension, agitation, earaches, hearing loss, and pseudotumor cerebri; CV: hypertension, arrhythmias, flushing, and hyperlipidemia; DERM: dry skin or mucous membranes, rash, pruritus, alopecia, mucositis; GI: nausea, diarrhea, constipation, and dyspepsia; HEMAT: leukocytosis; OCULAR: visual changes; OTHER: dyspnea, fever, shivering, and retinoic acid–APL syndrome (RA-APL syndrome: fever, dyspnea, weight gain, radiographic pulmonary infiltrates, and pleural or pericardial effusion).
Comments
TRIPTORELIN (TRELSTAR)
Mechanism of Action
Triptorelin is an LHRH agonist; chronic administration leads to sustained suppression of pituitary gonadotropins and subsequent suppression of serum testosterone in men and serum estradiol in women.
P.664
U.S. Food and Drug Administration–Approved Indications
Palliative treatment of advanced prostate cancer.
U.S. Food and Drug Administration–Approved Dosage
Trelstar Depot: 3.75 mg i.m. injection monthly.
Trelstar LA: 11.25 mg i.m. injection every 84 days.
Adverse Reactions
CV: hypertension and peripheral edema; ENDO: hot flashes, gynecomastia, breast pain, sexual dysfunction, and decreased erections; GU: erectile dysfunction, lower urinary tract symptoms, and testicular atrophy; OTHER: tumor flare in the first few weeks of therapy, bone pain, injection-site reactions, loss of bone mineral density, osteoporosis, bone fracture, and asthenia.
Comments
VALRUBICIN (VALSTAR)
Mechanism of Action
Valrubicin is an intercalating agent and topoisomerase-II inhibitor.
U.S. Food and Drug Administration–Approved Indications
Carcinoma in situ of the urinary bladder: second-line intravesical treatment after bacille Calmette-Guérin (BCG) therapy in patients for whom immediate cystectomy would be associated with unacceptable morbidity or mortality.
U.S. Food and Drug Administration–Approved Dosage
800 mg to be administered intravesically weekly × 6 weeks. For each instillation, 800 mg of valrubicin is diluted with 0.9% sodium chloride to a total volume of 75 mL. Once instilled into the bladder, the patient should retain drug in bladder for 2 hours before voiding.
Adverse Reactions
GU: Irritable bladder symptoms: urinary frequency, dysuria, urinary urgency, hematuria, bladder spasm, bladder pain, urinary incontinence, cystitis, local burning symptoms related to the procedure, and red-tinged urine.
Comments
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VINBLASTINE (VELBAN)
Mechanism of Action
Vinblastine inhibits microtubule formation.
U.S. Food and Drug Administration–Approved Indications
Palliative treatment of the following malignancies:
U.S. Food and Drug Administration–Approved Dosage
Initial (adults): 3.7 mg per m2 i.v. weekly. May increase weekly dose up to 18.5 mg per m2 to maintain WBC >3,000 cells per mm3 (package insert to be consulted for schema).
Initial (pediatric): 2.5 mg per m2 i.v. weekly. May increase weekly dose up to 12.5 mg per m2 to maintain WBC >3,000 cells per mm3(package insert to be consulted for schema).
Current literature may be consulted for alternative dosing regimens.
Dose Modification Criteria
Renal impairment: no dosage modification; hepatic impairment: dose to be modified; myelosuppression: dose to be modified.
Adverse Reactions
CNS: peripheral neuropathy, paresthesias, loss of deep tendon reflexes, and SIADH; CV: hypertension; DERM: alopecia, tissue damage or necrosis with extravasation; GI: N/V L1, stomatitis, constipation, and ileus; GU: urinary retention and polyuria; HEMAT: myelosuppression; OTHER: bone pain, jaw pain, tumor pain, weakness, malaise, and Raynaud phenomenon.
Comments
VINCRISTINE (ONCOVIN AND OTHERS)
Mechanism of Action
Vincristine inhibits microtubule formation.
U.S. Food and Drug Administration–Approved Indications
P.666
U.S. Food and Drug Administration–Approved Dosage
Dose Modification Criteria
Renal impairment: no dosage modification; hepatic impairment: dose to be modified.
Adverse Reactions
CNS: peripheral neuropathy, paresthesias, numbness, loss of deep tendon reflexes, and SIADH; DERM: alopecia, tissue damage or necrosis with extravasation; GI: N/V L1, stomatitis, anorexia, diarrhea, constipation, and ileus; GU: urinary retention, OCULAR: ophthalmoplegia, extraocular muscle paresis; PULM: pharyngitis; OTHER: jaw pain.
Comments
VINORELBINE (NAVELBINE)
Mechanism of Action
Vinorelbine inhibits microtubule formation.
U.S. Food and Drug Administration–Approved Indications
NSCLC: First-line therapy as a single agent (stage IV) or in combination with cisplatin (stage III or IV) for ambulatory patients with unresectable, advanced NSCLC.
U.S. Food and Drug Administration–Approved Dosage
Vinorelbine 25 mg per m2 i.v. over 6 to 10 minutes weekly, plus
Cisplatin 100 mg per m2 i.v. every 4 weeks
or
P.667
Dose Modification Criteria
Renal impairment: no dosage modification; hepatic impairment: dose to be modified; neurotoxicity: dose to be modified; myelosuppression: dose to be modified.
Adverse Reactions
CNS: peripheral neuropathy, and loss of deep tendon reflexes; CV: thromboembolic events, and chest pain; DERM: alopecia, vein discoloration, venous pain, chemical phlebitis, tissue damage or necrosis with extravasation; GI: N/V L1–2, stomatitis, anorexia, constipation, ileus, and elevated LFT values; HEMAT: myelosuppression (granulocytopenia greater than thrombocytopenia or anemia); PULM: interstitial pulmonary changes, and shortness of breath; OTHER: jaw pain, tumor pain, fatigue, and anaphylaxis.
Comments
REFERENCES