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© 2003 American Society for Clinical Oncology
In Reply:Baystate Regional Cancer Program, Baystate Medical Center, Springfield, MA, Tufts University School of Medicine, Boston, MA Gridelli and colleagues rightly state that challenges remain in the control of chemotherapy-induced nausea and emesis (CINE). This extends particularly to delayed CINE, which in recent years has received increased attention with regard to incidence, and more scrutiny with regard to prevention. They also describe the general reasons for not implementing guidelines,1 but postulate that underemployment of corticosteroids may be explained by patient-based clinical factors, specifically patient comorbidities and the risk of polypharmacy, and that these exceptions are reasonable, particularly in elderly patients. All patients have lists, of variable length, of active and inactive medical problems that require consideration when diagnosis and treatment is entertained; similarly, every patient requires a thoughtful review of their current medications and conditions in order to avoid drug interactions and contraindicated therapy. However, the implications of undertreatment should be considered equally. The use of a short course of dexamethasone, a corticosteroid with negligible mineralicorticoid activity, is unlikely to exacerbate hypertension that is well-controlled. Although hyperglycemia may be caused by glucocorticoids, patients known to be diabetic can be monitored and diabetic management altered if necessary. The consequences of CINE on these patients, which may result in noncompliance with essential medications, reduced caloric intake, and potentially inappropriate diabetic management, could pose a greater risk. In any event, such concerns did not seem to limit the usage of corticosteroids before chemotherapy, which was exceedingly high in our series,2 as in others.3–6 We do not believe that physician apprehension regarding exacerbation of comorbidities can explain the poor overall compliance with delayed CINE prophylaxis recommendations. We agree that polypharmacy is an issue for all patients, especially the elderly. However, CINE can degrade quality of life significantly, and they remain symptoms greatly feared by cancer patients.7 The relevance of the patient’s current medication regimen and the true risks of toxicity and drug interaction must be placed in the context of the reason for, and goals of, chemotherapy use and the concurrent obligation for appropriate supportive management. Patients with moderately-emetogenic chemotherapy receive postchemotherapy prophylaxis (when they receive it at all) most frequently with a 5HT3 receptor antagonist as a sole intervention or in combination with corticosteroids.2–6 The recent report by the Italian Group for Antiemetic Research8 of a randomized study of dexamethasone with or without ondansetron compared with placebo in this setting demonstrated that combination therapy resulted in more toxicity but no additional efficacy compared with dexamethasone monotherapy. Dexamethasone-associated insomnia (a major concern expressed by clinicians in our study2) was more prevalent in the combination arm than for dexamethasone alone (1% v 4.8%; Fisher’s exact test P = .03), and infrequent in both; dexamethasone-associated toxicities were not different than those found for placebo, including insomnia and gastrointestinal intolerance. While a relatively small proportion of patients enrolled onto this study were elderly, those enrolled (largely women treated for breast cancer) reflect the population of patients most frequently treated with chemotherapy.2,4,5 Although dexamethasone is the most frequently-employed corticosteroid in this setting, patients in our series receiving other corticosteroids (for example, prednisone in combination with cyclophosphamide, doxorubicin, and vincristine [the CHOP regimen]) were accepted as being in compliance if the dosage was equivalent to that recommended in the institutional guidelines. The widespread disuse of corticosteroids to prevent delayed CINE seems to represent a failure to offer routine therapy, proven safe and effective, rather than a case-by-case evaluation of appropriateness. As new antiemetic agents are implemented, most effectively in combination with corticosteroids,9 we must redouble our efforts to ensure that the majority of patients receive best-evidenced care; those that do not should be exceptions only for individualized, clinically-relevant, valid reasons. AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The following authors or their immediate family members have indicated a financial interest. No conflict exists for drugs or devices used in a study if they are not being evaluated as part of the investigation. Acted as a consultant within the last 2 years: Wilson C. Mertens, Merck & Co. Received more then $2,000 a year from a company for either of the last 2 years: Wilson C. Mertens, Merck & Co. REFERENCES
1. Cabana MD, Rand CS, Powe NR, et al.: Why don’t physicians follow clinical practice guidelines? A framework for improvement. JAMA 282:1458–1465, 1999
2. Mertens WC, Higby DJ, Brown D, et al: Improving the care of patients with regard to chemotherapy-induced nausea and emesis: the effect of feedback to clinicians on adherence to antiemetic prescribing guidelines. J Clin Oncol 21:1373–1378, 2003 3. De Angelis V, Roila F, Patoia L, et al: Impact on antiemetic prescriptions of the Consensus Conference (CC) and of an expert’s visit to oncological centers. Proc Am Soc Clin Oncol 19: 606a, 2000 (abstr 2386) 4. De Angelis V, Roila F, Sabbatini R, et al: Cancer chemotherapy (CT)-induced delayed emesis: Antiemetic prescriptions in clinical practice. Proc Am Soc Clin Oncol 22: 739, 2003 (abstr 2971) 5. Cohen L, de Moor C, Eisenberg P, et al: Chemotherapy-induced nausea and vomiting (CINV) remains a problem and significantly interferes with daily function (DF) in pts receiving emetogenic chemotherapy (CT) in the United States. Proc Am Soc Clin Oncol 22: 739, 2003 (abstr 2972)
6. Italian Group for Antiemetic Research: Transferability to clinical practice of the results of controlled clinical trials: The case of antiemetic prophylactic treatment for cancer chemotherapy-induced nausea and vomiting. Ann Oncol 9:759–765, 1998
7. Bernhard J, Maibach B, Thurlimann B, et al: Patients’ estimation of overall treatment burden: Why not ask the obvious? J Clin Oncol 20:65–72, 2002
8. Italian Group for Antiemetic Research: Dexamethasone alone or in combination with ondansetron for the prevention of delayed nausea and vomiting induced by chemotherapy. N Engl J Med 342:1554–1559, 2000 9. Warr D, Gralla RJ, Hesketh PJ, et al: The oral NK1 antagonist aprepitant for the prevention of chemotherapy induced nausea and vomiting: Two randomized, double-blind, placebo-controlled trials. Proc Am Soc Clin Oncol 22:726, 2003 (abstr 2919)
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Copyright © 2003 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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