NEW ORLEANS-Palonosetron (Aloxi) prevented chemotherapy-induced nausea and vomiting in older patients better than two other 5-HT3 receptor antagonists-ondansetron
NEW ORLEANSPalonosetron (Aloxi) prevented chemotherapy-induced nausea and vomiting in older patients better than two other 5-HT3 receptor antagonistsondansetron (Zo-fran) and dolasetron (Anzemet)and its extended half-life means that a single dose can prevent delayed nausea and vomiting, according to two posters presented at the 40th Annual Meeting of the American Society of Clinical Oncology.
Both posters reexamined data from the same two randomized, double-blind phase III studies. One study had compared efficacy of palonosetron and ondansetron, and the other had compared efficacy of palonosetron and dolasetron. The 754 subjects in the two studies were on moderately emetogenic chemotherapy. Patients were given a single intravenous dose of one of the antiemesis drugs 30 minutes before initiation of chemotherapy (most often cyclophosphamide, doxorubicin, or carboplatin [Paraplatin]).
In the study that contained dolasetron, some patients also received dexamethasone. The doses of the study drugs were 0.25 mg of palonosetron, 32 mg of ondansetron, or 100 mg of dolasetron.
Matti S. Aapro, MD, and his colleagues performed a retrospective analysis to compare the incidence of vomiting in a subset of 165 patients age 65 and older (abstract 8049). Dr. Aapro is director of the e-Learning Division, Multidisciplinary Institute of Oncology, Genolier Clinic, Switzerland. These researchers chose elderly subjects because they often have comorbidities and have a higher risk of treatment complications. "Therefore, simple, convenient treatment regimens are desirable in this population," Dr. Aapro said.
Endpoints were complete response (no vomiting and no rescue medication), vomiting episodes, nausea, and time to treatment failure (vomiting or use of rescue medication).
In the 5 days after chemotherapy administration, complete responses occurred significantly more often in patients taking palonosetron (70.9%) than in those taking either of the other drugs (52.1%; P = .011). In addition, more patients in the palonosetron group were free of nausea during those 5 days. The difference was statistically significant on days 2 and 3, when 66% and 68% of the palonosetron patients were nausea free, respectively, compared with 45% and 50% of the other patients.
Palonosetron was well tolerated in both studies, with adverse events occurring roughly as often as in the ondan-setron and dolasetron groups. The most common adverse effects in all groups were constipation, headache, and somnolence.
The researchers concluded that one dose of palonosetron was more effective in preventing chemotherapy-induced nausea and vomiting than a single dose of ondansetron or dolasetron in elderly patients. "We see no increase in side effects," Dr. Aapro said in an interview with ONI, "and we see the efficacy is maintained," compared with younger patients in the studies.
Another poster, presented by Steven M. Grunberg, MD, professor of medicine and pharmacology, Division of Hematology/Oncology, University of Vermont, Burlington, looked at the entire group of 754 subjects (abstract 8051).
Acute nausea and vomiting after chemotherapy are known to be the best predictors of delayed nausea/vomiting. The researchers sought to determine whether palonosetron prevented delayed nausea/vomiting solely as a carryover effect from its ability to prevent nausea/vomiting on day 1, or whether palonosetron truly has pharmacological effects that last throughout the first 5 days. Palonosetron has a 40-hour half-life, compared with 4 hours for ondansetron and 7.3 hours for dolasetron.
The researchers analyzed the data in two ways. In both analyses, the primary endpoint was complete response (no vomiting and no rescue medication) at 24 hours. The secondary endpoint was complete response from hour 0 to hour 120.
In the first analysis, the incidence of delayed nausea/vomiting was compared in patients who did and did not have acute nausea/vomiting. In patients who took palonosetron, 80% of the patients who did not experience acute nausea/vomiting also did not have delayed nausea/vomiting, compared with 69% of the patients taking one of the other antiemetics. In the palonosetron group, 23% of the patients who did have acute nausea/vomiting did not have delayed nausea/vomiting, compared with 12% of patients taking the other antiemetics. Both differences were statistically significant.
In the second analysis, the researchers performed a Bayesian logistical regression, taking into account factors that increase or decrease the risk of nausea/ vomiting, such as sex, age, and chemotherapy regimen. They created a carryover effect variable to represent how having vomited or having used rescue therapy on 1 day affected the outcome of the succeeding day.
They found that vomiting or needing rescue therapy on 1 day was the biggest predictor of whether the person would vomit or need rescue therapy the next day. However, patients on ondansetron or dolasetron had a higher relative risk of vomiting or needing rescue therapy on the day after vomiting or needing rescue therapy than did patients taking palonosetron.
Dr. Grunberg concluded: The fact that palonosetron prevented delayed nausea/vomiting just as well in patients who had acute nausea/vomiting as it did in those who did not provides evidence that palonosetron’s greater efficacy at preventing delayed nausea/vomiting is a true pharmacological effect and not just a carryover effect from the better prevention on day 1. As a result, Dr. Grunberg said in an interview with ONI, "we think that the extended half-life of palonosetron really does make a difference."