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Optimal Use of Antiemetics in the Outpatient Setting

Optimal Use of Antiemetics in the Outpatient Setting

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) antagonists—notably, ondansetron, granisetron, and 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.

Institutional Standards

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 or doxorubicin) and always administer
5-HT3 antagonists with 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
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.[1] Other groups have published similar guidelines intended to both
improve patient outcomes and control resource utilization.[2]

Understanding of Mechanisms

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