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Tuesday 13 September 2005

Delayed Nausea After Chemotherapy Poses Treatment Challenge

By: Hickok JT

Neither prochlorperazine nor first-generation 5-HT-receptor antagonists offer sufficient control of delayed chemotherapy-induced nausea, according to a study published in The Lancet Oncology.

Chemotherapy is often difficult for cancer patients due to severe nausea and vomiting. Despite significant progress over the past decade in controlling chemotherapy-induced nausea and vomiting (CINV), more than half of all patients receiving chemotherapy still suffer from these side effects. Furthermore, even when vomiting is controlled, nausea may persist. These symptoms can be severely debilitating and often lead patients to refuse further courses of chemotherapy. This minimizes chances for an optimal outcome. CINV can either be acute (occurring within the first 24 hours after chemotherapy), delayed (occurring more than 24 hours after chemotherapy), or both. Delayed nausea and vomiting is more common than acute nausea and vomiting.

Drugs to prevent nausea and vomiting (antiemetic drugs) can be given to patients before and after chemotherapy. In order to evaluate the effectiveness of two different types of antiemetics in preventing delayed chemotherapy-induced nausea, researchers conducted a randomized clinical trial of prochlorperazine and first-generation 5-HT-receptor antagonists (ondansetron, granisetron, and dolasetron). The study enrolled 691 patients from 18 private oncology practices in the US. None of the patients had had chemotherapy previously, and all were scheduled to receive the chemotherapy drug doxorubicin. All the patients received a 5-HT-receptor antagonist and dexamethasone before starting chemotherapy. On days two and three after chemotherapy, patients were randomized to receive one of three treatments: prochlorperazine given every eight hours regardless of symptoms, prochlorperazine given as needed, or any first-generation 5-HT-receptor antagonist.

A majority of patients in the study (77%) developed delayed nausea. Patients were more likely to have delayed nausea if they were younger (less than 53 years), female, or had had acute vomiting. Patients treated with prochlorperazine every eight hours were less likely than other patients to develop delayed nausea, but the proportion with delayed nausea remained “unacceptably high” in all treatment groups: Seventy-one percent of patients treated with prochlorperazine every eight hours had delayed nausea, compared to 79% of patients treated with 5-HT-receptor antagonists and 82% of patients treated with prochlorperazine as needed. There was no significant difference across treatment groups in the severity of the delayed nausea. Twenty-five percent of patients took additional medications to control nausea or vomiting.

The researchers conclude that none of the treatment approaches explored by this study adequately controlled delayed nausea, and that first-generation 5-HT-receptor antagonists are not better than prochlorperazine at preventing delayed nausea. The researchers note, however, that they did not evaluate more recently approved antiemetics such as aprepitant (an NK-1-receptor antagonist) or palonosetron (a second generation 5-HT-receptor antagonist).

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