Principles of Ambulatory Medicine, 7th Edition

Chapter 10

Care of the Patient with Cancer

Michael J. Purtell

Larry Waterbury

This chapter examines the role of the generalist in caring for patients who have cancer. Common cancers are discussed in other chapters (breast, Chapter 105; gastrointestinal, Chapter 45; gynecologic, Chapter 104; lung, Chapter 61; prostate, Chapter 53; skin, Chapter 114).Figure 10.1 depicts the estimated distribution of newly diagnosed cancers and cancer deaths for 2005. After initial diagnostic evaluation, the location of the primary cancer is unidentified in some patients with metastatic disease. The most common primary cancers that are eventually identified in such patients are cancers of the pancreas, lung, kidney, and colon (1). However, for 15% of such patients a primary is never identified after initial screening (syndrome of cancer with unknown primary). For these situations, an extensive search for the primary is not usually clinically useful. Therapy is based on the pattern of the metastases, and on the morphologic and immunochemical characteristics of the diagnostic tissue in conjunction with empiric guidelines derived from clinical trials testing various chemotherapy combinations. In the future, profiling the tissue with deoxyribonucleic acid (DNA) microarrays or selecting therapy with the use of proteomics, as well as further defining the extent of the cancer with such imaging modalities as positron emission tomography (PET) may become important (2,3).

General Aspects of Care

Communicating the Diagnosis

A patient's primary care provider is the one who is most likely to initiate diagnostic evaluation for cancer and to communicate the diagnosis to the patient. During these initial steps, the following elements are important: promptly scheduling tests and notifying the patient of results; communicating clearly; allowing the patient ample time to react to bad news. Almost always a referral to an oncologist should be considered. Treatment options and prognoses may change with new developments of which only the specialist may be aware. In the case of older (≥65; <75) patients, it is important that the primary care doctor does not unduly use age as a selection criteria when deciding if and to what subspecialty the patient should be referred. For example, it has been noted that whereas “fit” elderly (≥75) patients tolerate thoracic surgery as well as younger (<65) patients, many younger patients with early-stage lung cancer are referred to a thoracic surgeon, whereas the majority of elderly patients of similar potentially curable stage cancers are sent to the radiation oncologist, despite the underlining assumption that for early-stage lung cancer, surgery is the better option (4). Similarly, age should not be the major criteria when deciding between referral for hospice care or palliative chemotherapy (5). Irrespective of these considerations, it should be the role of the primary physician to promptly outline and explain, based on the type and extent of the cancer, what the patient's general options are and what the primary physician would recommend; to check the patient's understanding of information that has been given; and to include family members who the patient selects in all discussions regarding diagnosis, options, and prognosis. Chapters 3 and 4 discuss in detail approaches to communication with patients and their family members.

Initial Referral and Treatment

When possible, one should refer patients to oncologists whom one trusts and knows to be helpful, considerate clinicians. Multimodality treatment regimens involving the combined efforts of surgical, medical, and radiation oncologists may result in a bewildered patient without a

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clinician who accepts the primary responsibility for care. The patient's primary care practitioner should either coordinate care or identify who will be the coordinator for the patient's care and who will be accessible to the patient to answer questions, provide support, and ensure that necessary information is communicated. By receiving up-to-date and complete information about the diagnostic and therapeutic plans and the patient's evolving status, the primary care practitioner may be able to assess the overall picture and, as time goes on, identify when problems resulting from treatment (e.g., side effects, expense, family disruption, and deteriorating psychological status of patient) appear to outweigh the likely benefits of continued therapy. The treating oncologists will welcome such insights and consequently will consider a modification of the treatment regimen or will suggest a referral to a hospice program.

Followup Care

Most oncologists welcome participation of the patient's primary care practitioner in continuing care. This is particularly important when treatment is given in an oncology center in a distant city. Some less-toxic ambulatory treatment regimens and, particularly, symptom-management strategies may even be handled by the primary care practitioner under the direction of the specialist.

The followup of treated patients requires knowledge of the common sites and manifestations of tumor recurrence, the appropriate timing of followup examinations and tests, and a great deal of sensitivity in recognizing the feelings of the patient and the patient's family. Chapters elsewhere in this book on specific cancers discuss what is known and what is not known about the usefulness of followup assessments. Some patients function better if they are scheduled

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to be seen less frequently, so as not to be constantly reminded of the possibility of recurrence. Others require the constant reassurance of a negative examination and normal tests and are more comfortable with frequent followup visits. Usually there is room for considerable flexibility in a followup plan without jeopardizing the health of the patient.

Whenever a patient with cancer is seen in followup, it is important to explain carefully the meaning of symptoms or physical findings and the rationale for tests. If tests will take several days to return, that should be explained and a time for a telephone followup arranged.

It is possible in the future that tumor markers measured in the patient's serum—either to screen for cancer or to monitor therapy in patients with disseminated cancer—may be shown to be important in patient care. A critical analysis published in 1991 (6) and a more recent National Cancer Institute report (7) described potential roles for tumor markers in clinical decision making. Although tumor markers can be useful in monitoring the progress of known disease and the response to therapy, these are uses that benefit patients chiefly as part of the care plan of an oncologist or other specialist who is treating them. The routine use of tumor markers to screen for cancer in the asymptomatic patient remains potentially harmful, and there is no current consensus regarding any of the available markers, including the prostate specific antigen (see Table 14.2 and Chapter 53). Generally, it is inappropriate to monitor tumor markers routinely as part of the followup of patients with cancer who are potentially cured after primary and adjuvant therapy. This issue has been particularly well studied in patients with breast cancer (8). There are exceptions such as the use of the carcinoembryonic antigen (CEA) in colon cancer, the cancer antigen (CA)-125 in ovarian cancer, or β-human chorionic gonadotropin (β-hCG) in testicular cancers. The National Cancer Comprehensive Network publishes guidelines for the followup strategies of most cancers. These are available at its website:http://www.nccn.org/professionals/physician_gls/license_agreement.asp. Recommendations are ranked based on evidence-based criteria and degree of consensus among contributing experts.

Family Concerns

The crises attending evaluation for possible cancer and the diagnosis and care for cancer profoundly affect the spouses and families of patients. Common dilemmas for family members include emotional strain, physical demands in caring for the patient, altered roles and lifestyles, finances, and uncertainty about prognosis (9). In addition, there may be questions about the likelihood of cancer occurring in other members of the family. Each of these issues may require consideration by the patient's primary care practitioner (for details, see chapters on specific cancers and Chapters 13, 17, and 20).

Support from the American Cancer Society

The American Cancer Society has chapters in each state and can provide a variety of services to patients and their families. Services vary among states but may include loan of supplies (e.g., hospital beds), transportation to treatment facilities, reduced costs for chemotherapy, respite coverage for caregivers, and a wide range of information about support groups and other help available in the patient's community.

Nonoperable Cancers in which Treatment may Prolong Survival

Table 10.1 lists a number of nonoperable cancers in which survival may be prolonged by modern treatment regimens; patients with such cancers need ongoing followup with cancer specialists. These patients often benefit from multimodality treatment. Even within this group of cancers, when specialty help is needed, the primary care practitioner continues to play an important role, especially if the relationship with the patient or the family has been a lengthy one.

Cancers Poorly Responsive to Treatment

Table 10.2 lists a number of nonoperable cancers that are less responsive to therapy, where the impact of therapy on survival is unproven or minimal. Diagnosis and initial therapy for limited stage disease usually require surgery,

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but when metastasis is proven, the effect of systemic therapy, radiotherapy, or both, is at most palliative. In such situations, patients often expect their primary care practitioners to help them select or recommend treatment plans. Several questions come up at this juncture.

Should palliative chemotherapy be recommended? Although it is difficult to generalize, several factors must be considered in attempting to help patients and their families decide whether the patient is likely to benefit from palliative chemotherapy. More than age, the functional status of the patient must be considered in such therapeutic decisions. The infirm, ill, poorly functional patient with widely disseminated and rapidly progressive disease may be more harmed than benefited by the side effects and discomforts of palliative treatment, especially if response rates are small and toxicity of treatment is high. Weight loss before therapy correlates closely with poor response rates in clinical chemotherapy trials in these less-responsive cancers (10). Other patients, even if elderly, who are in good functional status are much more suitable candidates for attempts at palliation (11). For example, elderly patients with metastatic lung cancer, but otherwise in good health, given systemic chemotherapy appear to maintain their quality of life longer than similar elderly patients given only supportive care. These findings mirror those observed with younger patients (4,5). The patient who believes that any chance of response is worth the price of toxicity and who cannot feel comfortable unless attempting some therapy, should generally be offered treatment.

If some attempt at palliative treatment seems worthwhile, should it be conventional therapy or experimental protocol therapy? Every oncology center has current protocols for the metastatic cancers listed in Table 10.2. Clinical protocols designed to seek improved methods of treatment are important for advances that may improve the outlook and the comfort of future patients. However, experimental therapy may have undesirable consequences for the individual patient. Sometimes, such protocols involve the investigation of treatments with more toxicity than current conventional therapies. They may require more frequent visits to the clinician and more frequent diagnostic tests, because of the necessity to document precisely the objective response. They may therefore also involve increased expense to the patient. The patient's insurance may or may not cover the specific experimental therapy being considered. Patients agreeing to experimental protocol therapy—and their practitioners—must be well informed about the side effects and likely benefits of therapy (12,13). The helpful consultant should describe the current conventional treatment for the patient's disease and tailor the recommendation to the specific patient. No treatment, conventional palliative chemotherapy or radiotherapy, or experimental therapy are appropriate choices for individual patients depending on their situations and preferences. Table 10.3 lists the major factors for patient and clinician in selecting among these options.

Radiotherapy

Patient Experience

The patient with cancer often has misconceptions about and limited knowledge of radiotherapy. It is thus important to explain radiotherapy to the patient in terms of the rationale, patient experience, and likely benefits and side effects of this treatment modality. The initial visit usually includes a complete history and physical examination by the radiotherapist. Further diagnostic tests (e.g., radiographs and computed tomography) may be obtained. If the therapist agrees that treatment is appropriate and urgent, the radiotherapy ports may be determined at the first visit and the patient may receive his or her first treatment at that time. The patient is told that skin tattoos may be placed to facilitate the uniformity of subsequent treatments. It is important to explain that the therapy machines are bulky and somewhat overwhelming in appearance. Some patients are frightened by the experience. This may be particularly so with techniques such as stereotactic-based radiosurgery (i.e., gamma knife), which rely on extremely accurate targeting of the tumor. To achieve or maintain the necessary precision, the patient is immobilized in a brace to prevent undue motion. These procedures will become more

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commonplace as studies supporting their benefits—already shown for the treatment of brain metastases—become available (14). If the referring clinician appreciates this, it is useful to contact the radiotherapist and to explain the particular fears of the patient ahead of time. Therapists often give patients and their families a tour of the radiotherapy treatment rooms before starting therapy and spend extra time answering questions about the treatment and its benefits and complications. The patient should be aware that the treatments themselves are not painful. The initial consultation is usually time-consuming (several hours), but subsequent treatments are usually scheduled precisely and frequently require only a small amount of time (15 to 30 minutes). Treatments are usually given several days a week and the entire course may take several weeks to complete. The patient usually does not see the radiotherapist at the time of each treatment but is seen by a radiotherapy nurse or technician. Consequently, the patient needs to know precisely with whom to communicate to address side effects or questions during radiotherapy.

Time Until Symptomatic Response

In addition to the timing and types of side effects that may be experienced, it is important for the patient to know that the response to treatment is often delayed and that sometimes the maximal effect is noted a few weeks after the course of radiotherapy is completed. For example, radiotherapy is useful in the palliation of pain secondary to local bony metastases, but 2 to 3 weeks may elapse before improvement occurs and improvement may not be maximal until a few weeks after treatment is discontinued. Some responses are more rapid, occurring after only a few days of therapy (e.g., relief of superior vena cava obstruction and neurologic deficits from spinal cord obstruction or central nervous system metastasis).

An excellent booklet, Radiation Therapy and You: A Guide to Self-Help During Treatment, is available free from the National Institutes of Health to patients undergoing radiotherapy (see http://www.hopkinsbayview.org/PAMreferences). It is helpful to have copies of this booklet available for patients and families to read when radiotherapy is being considered.

Side Effects

Table 10.4 describes important side effects of radiotherapy. The patient will be most concerned by the common side effects that occur during treatment and by those that may remain for a few weeks after treatment is discontinued.

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Dermatitis secondary to radiotherapy is less common than it used to be because of the use of the modern high-energy machines. Severe burning requiring specialized treatment is uncommon; however, skin discoloration may occur. The patient should be told that the radiation field should not be exposed to sunlight or extreme cold, that total but temporary hair loss will usually occur in the areas being radiated and that complete return of hair, after high-dose radiation, may take many months or may not occur.

The most troublesome side effects that occur during radiotherapy are gastrointestinal. Patients receiving radiation to the chest or upper back often experience symptoms of radiation esophagitis (odynophagia and sometimes reflux symptoms that may respond to elevation of the head of the bed and to antacids). Severe esophagitis is more likely to occur when radiotherapy has been used in patients who have had prior chemotherapy, especially with such agents as doxorubicin, bleomycin, or cis-platinum. Candida superinfection of the irritated esophagus is not unusual, especially in patients who are receiving steroids. This usually responds well to treatment with fluconazole (100 mg daily). Patients should improve with a 1-week course of therapy. Abdominal irradiation can cause diarrhea that may persist to some degree during the entire course of treatment. In addition to replacing fluids and electrolytes, some dietary maneuvers may minimize diarrhea; these are listed in Table 10.5. Nausea and anorexia are the most troublesome side effects of abdominal irradiation and are discussed separately later in this chapter.

Patients who receive radiotherapy to the head or neck are subject to oral and dental complications. Before treatment, all patients should have a complete dental examination by a dentist experienced in the treatment of patients who have undergone radiotherapy. Damage to the teeth, gums, and bone, plus the xerostomia that results from high-dosage radiotherapy to the oral mucous membranes and salivary glands, may result in severe problems. Many of these can be prevented by appropriate prophylaxis (aggressive treatment of periodontal disease and infected teeth before radiation) and an ongoing program during and after radiotherapy, which should be strictly followed. The use of artificial saliva (Saliva Substitute, Roxane Laboratories) may be helpful for patients with xerostomia.

Corticosteroids and Radiotherapy

The patient's primary care practitioner may sometimes be involved with the early treatment of central nervous system metastases or spinal cord compression, using corticosteroids in conjunction with radiotherapy. Multiple regimens are used. A common regimen consists of dexamethasone (Decadron), 4 to 25 mg four times a day, continued until the patient has received several courses of radiotherapy and then slowly tapered over 2 to 3 weeks. Steroids decrease the local edema that occurs in these situations and help protect against radiation-induced edema during the first few days of therapy. Despite the use of steroid, a patient receiving spinal radiation for a cord compression syndrome may rarely experience sudden neurologic deterioration during the initial period of treatment because of radiation-induced edema. This demands an emergent evaluation by a neurosurgeon for possible decompression laminectomy.

Cumulative Dosage

A maximal cumulative dosage of radiotherapy can safely be given to any one site without the risk of significant permanent tissue damage. This dosage varies for each organ system. If ports do not overlap, definitive full-dose radiotherapy can be given to multiple sites either concomitantly or sequentially. Problems occur when ports are contiguous or overlapping. For example, it is often more beneficial to give palliative total spine irradiation to patients with several isolated spine metastases than to treat only focal symptomatic areas, which may preclude later palliative radiotherapy to symptomatic contiguous areas.

Chemotherapy

Patient Experience

The chemotherapy experience for the patient is so varied (depending on the disease being treated) that it is hard to give a general description. The medical oncologist giving therapy can best explain to the patient the specifics of treatment, including how it is administered, the frequency of treatment, the hoped-for response, and the side effects. The most common troublesome side effects for the patient are hair loss and nausea and vomiting. The frequency and degree of hair loss vary with the treatment regimen, but it is helpful for the patient to know that hair will regrow once the treatment is discontinued. The treatment of nausea and vomiting is discussed later in this chapter (see Nausea, Vomiting, and Anorexia). Table 10.6 lists other acute and chronic side effects of various chemotherapeutic agents. Knowledge of the long-term side effects of various agents is particularly important for the primary care practitioner, who may be responsible for followup care of patients with good prognoses after chemotherapy.

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An excellent free booklet, Chemotherapy and You: A Guide to Self-Help During Treatment, written for patients, is available through the National Institutes of Health (see http://www.hopkinsbayview.org/PAMreferences). It is helpful to have this booklet available for patients and families to read when chemotherapy is being considered.

Chemotherapy-Induced Granulocytopenic Fever

The most common side effect of cytotoxic chemotherapy is myelosuppression and the associated risk of systemic infection (15). Granulocytopenia is defined as an absolute neutrophil count of <1,000 cells/mm³. However, a significant risk of infection is not incurred until the concentration falls below 500 cells/mm³. In particular, the incidence of culture-proven septicemia correlates best with the number of days a patient remains with a neutrophil count below 100 cells/mm³. The nadir of the white count, and hence the largest risk of serious infection, usually occurs 10 to 14 days after chemotherapy is administered. It is the responsibility of the treating oncologist to monitor the neutrophil counts and to instruct patients when to check their temperatures and when to seek help if a fever or other signs (e.g., malaise, chills, cough) of infection develop. However, there may be circumstances when the patient's primary care practitioner may be contacted by the patient.

It has been dogma that any granulocytopenic patient is at great risk for gram-negative bacteremia, especially Pseudomonas, and that all febrile neutropenic patients need immediate hospitalization with appropriate empiric antibiotic coverage. For the primary care practitioner, who may not have the patient's latest hemogram and who may not have followed the recent course of the patient, this still may be the best guideline. On admission the patient should have blood and urine cultures and a chest radiograph. A history of new symptoms and an examination guided by symptoms, but always including attention to the mouth, skin, and perirectal area, may reveal a source. Unlike unimpaired patients, immunocompromised patients can have a life-threatening septicemia with few or no focal signs or symptoms. Therefore, instead of watching and waiting at the time of admission, one should initiate treatment with broad-spectrum antibiotics such as a semisynthetic penicillin and an aminoglycoside or third- or fourth-generation cephalosporin to which Pseudomonas is sensitive. In recent years, the incidence of Pseudomonas bacteremia has markedly decreased in these patients; Escherichia coli and Klebsiella pneumoniaeremain the most common infections, and the incidence of gram-positive infections, especially coagulase-negative staphylococci, has risen, probably because of the increased use of indwelling venous access devices. On occasion, when the patient is not sick and the expected length of neutropenia is short,

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the experienced oncologist may elect to treat the febrile neutropenic patient as an outpatient. The quinolones are most commonly used. When gram-positive infections are suspected, clindamycin and amoxicillin/potassium clavulanate are frequently used.

Nausea, Vomiting, and Anorexia

Nausea and vomiting can be the most troublesome side effects of radiotherapy and chemotherapy. In the past, the symptomatic treatment of nausea was only moderately effective, and vomiting was particularly troublesome with therapies containing cis-platinum. However, antiemetic regimens combining corticosteroids (dexamethasone, 10 to 20 mg either intravenously or orally) with an HT₃ serotonin blocker (e.g., ondansetron, 15 to 30 mg intravenously or orally) have greatly reduced the incidence of nausea and vomiting in the first 24 hours after therapy with cis-platinum and other strongly emetic regimens (16; NCCN website at: http://www.nccn.org). Oral serotonin blockers can be helpful for ongoing nausea from radiotherapy and chemotherapy. Lorazepam may have a role in relaxing the anxious patient before chemotherapy, and because of its interference with short-term memory, it may also lessen the chance of a patient developing anticipatory nausea (17). The nausea of less emetogenic regimens usually can be controlled with a 10- to 20-mg dose of dexamethasone and a lower dose of an HT₃ serotonin inhibitor. Prochlorperazine, preferably 10 mg intravenously, can be effective for acute emesis; 10 mg orally or 25 mg rectally can be used for more chromic nausea. Nausea that begins 1 or 2 days after the administration of the chemotherapy and lasts for a week or more is still a difficult problem to treat, especially after administration of cis-platinum. Attempts to treat with a short course of oral dexamethasone (8 to 12 mg/day) or with prochlorperazine (one or two 10-mg capsules orally or a 25-mg suppository every 4 to 6 hours) are only moderately successful. Once developed, delayed nausea is usually not helped by oral serotonin blockers. However with the recent introduction of the antiemetic aprepitant (an inhibitor of neurokinin 1 receptors) and of palonosetron, a serotonin 5HT₃ receptor inhibitor with a prolonged biologic half-life, delayed nausea and vomiting are less of a problem (18). In addition to pharmacologic palliation, the patient with marked nausea will find that it is often helpful to be extremely still, lying down in a quiet room without external stimuli. Even with the improvements in therapy for chemotherapy-induced nausea, patients still consider nausea and vomiting among the most troublesome side effects of chemotherapy (19).

A number of dietary maneuvers may be helpful to the patient experiencing nausea and vomiting after therapy. The patient who experiences severe nausea and vomiting after therapy should probably drink only clear liquids until the symptoms are decreased. In general, it is more helpful to take smaller portions of food frequently than to take larger meals less often, to take foods that are low in fat, and to avoid overly sweet foods. Mild nausea, especially that experienced before therapy or in anticipation of therapy, may be helped by taking dry toast or crackers in small quantities. It is recommended that patients not lie down just after eating. Some patients find also that it is helpful not to drink liquids with their food (because this may increase their feeling of bloating and subsequent nausea). Many patients become nauseated at the smell of food cooking, and it may be helpful for them to go to another part of the house or to stay out of the house when food is being prepared. Greasy and fried foods seem to be the worst offenders in this regard and are best avoided.

A major problem with intensive cancer therapy is general anorexia, which is often associated with alterations in taste and smell and which may result in considerable nutritional problems and weight loss (20). Consultation with a dietitian may be helpful in such a situation. Oral progesterone (Megace) in large doses (300 to 800 mg/day) may be helpful for the patient with persistent anorexia (21). Dexamethasone in dosages of 2 to 4 mg twice per day can also be used. The steroid side effects restricts its use to acute brief episodes or end-of-life situations. Some studies show that oxandrolone, a weak anabolic steroid, preserves muscle mass better than other agents. Because it does not have any immunosuppressive properties, it may be more suited for those patients still receiving chemotherapy (22). Its expense limits its use.

An excellent free booklet, Eating Hints for Cancer Patient: Before, During, and After Treatment, is available through the National Cancer Institute (see http://www.hopkinsbayview.org/PAMreferences). It contains all sorts of dietary advice for patients with cancer, including many recipes.

Terminal Care

The primary care practitioner who has participated in various phases of cancer care and who has an ongoing relationship with the patient and his or her family is often in the best position to help during a patient's terminal illness. The practitioner who develops some expertise in this regard can find enormous gratification from this role. Chapter 13 deals with many of the issues important in caring for terminally ill patients and their families, including the very important issues of pain control, hospice care, and bereavement. An excellent publication,Coping with Cancer: A Resource for the Health Professional, is available free of charge from the National Institutes of Health (seehttp://www.hopkinsbayview.org/PAMreferences). In addition to other useful information, it lists organizations and agencies that provide useful services that may aid the practitioner in providing support for the dying patient.

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Specific References*

For annotated General References and resources related to this chapter, visit http://www.hopkinsbayview.org/PAMreferences.

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