Management of Adverse Effects

Nausea and Vomiting
Antiemetics prevent or relieve nausea and vomiting, which commonly occurs with radiotherapy to the abdomen and with many chemotherapeutic drugs, especially when given in combination. Sometimes the nausea and vomiting is functional or due to the cancer itself. Therefore, the underlying cause should always be sought and corrected.

Stimulation of the vomiting center in the medulla can arise in the chemoreceptor trigger zone (CTZ), cerebral cortex, or vestibular apparatus or can be relayed directly from peripheral areas (eg, gastric mucosa). Antiemetics appear to act in these areas, but their mechanism of action is not well understood. Generally, drug therapy is more successful for prophylaxis than for treatment of nausea and vomiting.

Serotonin-receptor antagonists are the most effective drugs available for the management of nausea and vomiting associated with radiotherapy or chemotherapy and with many disease processes. Virtually no toxicity occurs with granisetron and ondansetron, although headache and, rarely, orthostatic hypotension have occurred with ondansetron. These drugs are first-line antiemetic therapy; their major drawback is expense.

Antidopaminergics include many of the phenothiazines (eg, prochlorperazine, fluphenazine), which appear to act by selectively depressing the CTZ and, to a lesser extent, the vomiting center. These second-line drugs are useful in treating mild to moderate nausea and vomiting. Because most phenothiazines (except thioridazine and mesoridazine) appear to be equally effective if given in sufficient dosage, the choice of drug may depend on consideration of side effects.

Metoclopramide stimulates the motility of the upper GI tract, increases the tone and amplitude of gastric contractions, and increases duodenal and jejunal peristalsis. The result is accelerated gastric emptying and intestinal transit.

Metoclopramide functions as an antiemetic by its gastrokinetic effects and, in addition, appears to have some central dopamine antagonist actions. The most important side effects are extrapyramidal symptoms, which are in part dose-related. Benadryl will protect from these. Other side effects include drowsiness and fatigue. The drug is contraindicated when stimulation of GI motility might be dangerous (mechanical obstruction or perforation), in pheochromocytoma, and in epileptics or in patients receiving other drugs likely to cause extrapyramidal reactions. Its use as an antiemetic has largely been replaced by the serotonin-receptor antagonists.

Dronabinol, Δ-9-tetrahydrocannabinol (THC), is approved to treat nausea and vomiting caused by chemotherapy in patients unresponsive to conventional antiemetic treatment. THC is the principal psychoactive component of marijuana. Its mechanism of antiemetic action is unknown, but cannabinoids bind to opioid receptors in the forebrain and may indirectly inhibit the vomiting center. The drug has largely been abandoned because it has variable oral bioavailability, is ineffective against the nausea and vomiting of platinum-based chemotherapy regimens, and has significant side effects (eg, drowsiness, orthostatic hypotension, dry mouth, mood changes, visual and time sense alterations).

Cytopenias
Anemia, leukopenia, and thrombocytopenia may develop during radiotherapy or chemotherapy. Clinical symptoms and decreased efficacy of radiotherapy occur at Hct levels < 30%. Although packed RBC transfusions are rarely needed, recombinant erythropoietin is used to manage the cancer fatigue and RBC requirement. In general, 100 to 150 U/kg sc three times/wk (a convenient adult dose is 10,000 U) is very effective and has reduced or eliminated the need for transfusions. Significant thrombocytopenia (platelet count < 10,000/mL), especially if bleeding is present, can be managed with transfusions of platelet concentrates. Recombinant thrombopoietin is available and will likely markedly reduce such transfusion needs.

Neutropenia (absolute neutrophil count < 1000/μL) is the most clinically relevant cytopenia because neutropenic fever and an increased risk of infection occur. Fever > 38° C (100.4° F) in a granulocytopenic patient should be regarded as an emergency. Evaluation of the neutropenic patient should include immediate cultures of blood, sputum, urine, and stool. The examination should focus on possible abscess sites (eg, retina, ears, rectum). Because the absence of neutrophils means that the expected signs of recognition of an abscess may not be evident, focal pain and tenderness may be clues to an incipient abscess.

A stable patient may be treated with an intensive outpatient regimen at many institutions, but in the absence of a defined program, hospitalization is needed. Treatment with broad-spectrum antibiotics should be started immediately after cultures of the blood, sputum, urine, and any suspicious skin lesions are obtained. If diffuse pulmonary infiltrates are present, the physician should include Pneumocystis carinii pneumonia in the differential diagnosis and institute empiric therapy, especially in patients with leukemia or lymphoma. In the presence of such infiltrates, the antibiotic regimen should include trimethoprim-sulfamethoxazole, an aminoglycoside, and a cephalosporin. In patients with an indwelling venous catheter, gram-positive infections are common and vancomycin should be added. If fever continues after 24 h, a semisynthetic penicillin (eg, ticarcillin) should be added. If fever continues for 72 to 120 h, a fungal etiology should be considered and amphotericin B should be added to the therapy program.

An important therapeutic addition during neutropenic sepsis or fever is cytokine therapy with granulocyte colony-stimulating factor (G-CSF-or alternatively granulocyte-macrophage colony-stimulating factor [GM-CSF]). G-CSF (5 μg/kg/day sc or by infusion) is the drug of choice and should be instituted at the onset of fever or sepsis.

Other Common Adverse Effects
Enteritis from abdominal radiotherapy can be alleviated with antidiarrheal drugs. Mucositis from radiotherapy can preclude substantial oral intake and lead to malnutrition and weight loss. Simple measures (eg, use of analgesics and topical lidocaine before meals, a bland diet without citrus food or juices, avoidance of temperature extremes) allow the patient to eat and maintain weight. If these simple measures fail, enteral alimentation with a flexible plastic tube (Dobhoff) may be considered as long as the small intestine is functionally normal. In cases of mucositis and diarrhea or an abnormally functioning bowel, parenteral alimentation may be substituted. Pain may be a problem but can be treated with drugs, focal radiotherapy, or surgery. Similarly, depression must be recognized. Frank discussion of a patient’s fears can often relieve anxiety; a growing armamentarium is now available for treatment of depression.

Incurable Cancer

A common misconception is that some cancers are untreatable. Although the cancer may be incurable, the patient can be treated. Treatment means more than the use of surgery, radiotherapy, or chemotherapy; it means the wise care of the patient. For patients whose cancers are not responsive to these modalities, use of an ineffective chemotherapy drug to be “doing something” to the cancer is poor medicine. Appropriate therapy for such patients (and for all cancer patients) includes nutritional support, effective pain management, relevant palliative care, and psychiatric and social support. Above all, the patient must know that the clinical team will not abandon him because specific therapy does not exist or has not been effective. Participation in well-controlled research trials, if available and appropriate, should be considered and discussed with the patient. Hospice or other related end-of-life care programs are important parts of cancer treatment.

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Provided by ArmMed Media
Revision date: July 7, 2011
Last revised: by Janet A. Staessen, MD, PhD