In his article, Dr. Grunberg charts the history of our understanding of chemotherapy-induced nausea and vomiting, and the discovery and development of drugs for its prevention. He places appropriate emphasis on the serotonin (5-HT3) antagonistsnotably, ondansetron(Drug information on ondansetron), granisetron(Drug information on granisetron), and dolasetron(Drug information on dolasetron)which have revolutionized the field over the past decade.
As detailed by Dr. Grunberg, these drugs have not only proven to be extremely effective in the prevention of acute, chemotherapy-induced emesis, but are also extremely flexible in schedule and route of administration, with remarkably few side effects. This has led to the rapid adoption of these drugs in clinical practice, and their popular use. An important problem not addressed by Dr. Grunberg in this article is how to control the cost of these agents, which can total hundreds of dollars per day.
At Memorial Sloan-Kettering Cancer Center (MSKCC), we have established an Antiemetic Subcommittee comprised of physicians, nurses, and pharmacists, to maintain institution-specific guidelines for the administration of antiemetic agents. Our recommendations are based on considerations such as the dose-response curves of various antiemetic agents. As detailed by Dr. Grunberg, the 5-HT3 antagonists have logarithmic dose-response curves, which rapidly reach a therapeutic plateau and reflect long half-lives of 5 to 10 hours. This accounts for the clinical effectiveness of a single, up-front dose of a 5-HT3 antagonist for acute emetic prophylaxis, which is our institutional standard.
We limit the automatic use of these agents to patients receiving chemotherapy likely to cause vomiting (eg, cisplatin(Drug information on cisplatin) or doxorubicin(Drug information on doxorubicin)) and always administer 5-HT3 antagonists with dexamethasone(Drug information on dexamethasone) to enhance the effectiveness of the regimen. We also use a 5-HT3 antagonist/dexamethasone combination for the prevention of delayed emesis. A combination of dexamethasone and metoclopramide(Drug information on metoclopramide) is a good alternative regimen for delayed emesis.
As a result of our guidelines, patients at MSKCC have demonstrated excellent tolerance of emetogenic chemotherapy, accompanied by an increase in antiemetic use, yet a dramatic decrease in antiemetic drug expenditures across the institution. Other groups have published similar guidelines intended to both improve patient outcomes and control resource utilization.
Understanding of Mechanisms