Making chemotherapy easier

Article Abstract:

Although not all chemotherapeutic agents lead to severe nausea and vomiting, the ones that do may cause patients to stop treatment before its effects are complete. This has led to research efforts to develop drugs that work against vomiting (antiemetic agents). Chemotherapy leads to vomiting in at least three ways. Receptor molecules on the surfaces of cells in the brain respond to chemicals; nerve endings in the digestive system are stimulated, triggering the reflex; and emotional pathways are activated by fear and odors associated with past vomiting. Since receptors for dopamine are found in both the emetic center in the brain and the gastrointestinal tract, antiemetic drugs have usually worked by blocking dopamine's effects. Two studies in the March 22, 1990, issue of The New England Journal of Medicine report success with a new kind of drug that blocks the action of serotonin, a substance associated with migraine headache, appetite, and mood control. It appears that serotonin receptors, located in both the gastrointestinal tract and the central nervous system, are the main mediators of the vomiting reflex. The reports used ondansetron, a serotonin receptor blocker, after chemotherapy with cisplatin, one of the most powerful emetogenic (nausea-causing) agents. Odansetron was found to be more effective in reducing vomiting than metoclopramide, the previously most effective preparation. Furthermore, one study found an increase in the concentration of a metabolite, a breakdown product, of serotonin in patients' urine after they had received cisplatin, indicating that serotonin is fundamentally important to the emetic reflex. In evaluating different antiemetic agents, it appears that the chemotherapeutic substance must be taken into account; some drugs that work after fluorouracil do not work after cisplatin. It can be especially difficult to evaluate the antiemetic effectiveness of drugs after chemotherapy treatments that do not induce vomiting in all patients. More standardized criteria for evaluating the emetogenic properties of chemotherapy, as well as the antiemetic potential of new drugs, are called for. (Consumer Summary produced by Reliance Medical Information, Inc.)

editorial

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Comparison of the 5-hydroxytryptamine 3 (serotonin) antagonist ondansetron (GR 38032F) with high-dose metoclopramide in the control of cisplatin-induced emesis

Article Abstract:

Nausea and vomiting are two of the most unpleasant side effects after treatment with cisplatin, a potent chemotherapeutic agent for many forms of cancer. No currently available antiemetic (anti-vomiting) agent is completely effective against these side effects; metoclopramide, one of the most effective, only establishes complete control of vomiting in 38 to 60 percent of patients. The effectiveness of metoclopramide was compared with that of odansetron in 97 patients undergoing treatment with cisplatin. Patients received one drug at the first treatment, then the other at the second treatment, and alternated the drugs they received throughout the study. Analysis of data from the 76 patients who completed the study showed that vomiting was completely or nearly completely controlled for 75 percent of patients on odansetron but only 42 percent for those on metoclopramide. Moreover, odansetron was more effective in controlling acute nausea. It is likely that the effectiveness of odansetron is due to its ability to block the action of serotonin, a chemical that acts on the central nervous system to induce vomiting. (Consumer Summary produced by Reliance Medical Information, Inc.)

Metoclopramide

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Reduction of cisplatin-induced emesis by a selective neurokinin-1-receptor antagonist

Article Abstract:

A drug that blocks the neurokinin-1 receptor appears to be effective in preventing nausea and vomiting in cancer patients who take cisplatin. The neurokinin-1 receptor is a receptor for substance P, which can cause vomiting. Researchers randomly assigned 159 patients who were starting treatment with cisplatin to take a drug called L-754,030 or a placebo after taking a single dose of cisplatin. The drug suppressed immediate vomiting in 93% of the patients who took it, and delayed vomiting in 82%. The figures for the placebo group were 67% and 33%, respectively.

Prevention, Vomiting

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