palonosetron and Acute-Disease

Despite the advance in supportive care that occurred with the introduction of selective serotonin subtype 3 (5-HT3) receptor antagonists, control of chemotherapy-induced nausea and vomiting (CINV) with first-generation agents (ondansetron, dolasetron, and granisetron) is less than ideal. Palonosetron is a unique 5-HT3 receptor antagonist whose distinctive pharmacologic characteristics (ie, high 5-HT3 receptor binding affinity, prolonged half-life) result in superior clinical benefit. Superiority of palonosetron over ondansetron and dolasetron in the prevention of both acute and delayed CINV has been observed in each phase III trial conducted. Of note, such evidence of superiority has never been seen in US Food and Drug Administration (FDA) registration trials of other approved agents in this class. Recently approved by the FDA, palonosetron 0.25 mg intravenously is indicated for the prevention of acute nausea and vomiting associated with initial and repeat courses of moderately and highly emetogenic cancer chemotherapy. Unlike other 5-HT3 receptor antagonists, palonosetron is also indicated for prevention of delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy. Palonosetron exhibits an excellent tolerability profile, with frequency, severity, and duration of adverse reactions similar to that of comparator agents. Unlike older agents that are considered therapeutically interchangeable at equipotent doses, palonosetron should be considered a clinically distinct and superior treatment for the prevention of CINV.

Topics: Acute Disease; Adult; Aged; Antiemetics; Antineoplastic Agents; Clinical Trials as Topic; Cytochrome P-450 CYP2D6; Dexamethasone; Female; Half-Life; Humans; Indoles; Isoquinolines; Male; Middle Aged; Nausea; Neoplasms; Ondansetron; Palonosetron; Protein Binding; Quinolizines; Quinuclidines; Serotonin 5-HT3 Receptor Antagonists; Serotonin Antagonists; Vomiting

Palonosetron and ondansetron are two selective 5-hydroxytryptamine (5-HT3) receptor antagonists that have shown remarkable efficacy in controlling nausea and vomiting following administration of moderately emetic anticancer chemotherapy. Their efficacy is enhanced by the concurrent administration of dexamethasone. In the present study, we aimed to compare the antiemetic efficacy of a palonosetron plus dexamethasone (PD) schedule versus an ondansetron plus dexamethasone (OD) schedule.. A randomised, crossover trial was conducted in 30 patients with head and neck cancer who were receiving moderately emetogenic chemotherapy. The patients were divided into two groups. In the first cycle, one group was given a PD schedule and the other, an OD schedule. For the subsequent cycle, crossover of the antiemetic schedules was done. The antiemetic effects were evaluated by recording the intensity of nausea and the frequency of vomiting in the acute and delayed phases.. Complete response in the acute phase was observed in 83.3 percent of the patients on the PD schedule and in 80 percent of those on the OD schedule. In the delayed phase, complete response was observed in 76.7 percent and 66.7 percent of the patients on the PD schedule and OD schedule, respectively. The overall rate of complete response was 66.7 percent in the PD group and 46.7 percent in the OD group. In the PD group, there were 73.3 percent of nausea-free patients as opposed to 66.7 percent in the OD group.. The results suggest that the PD schedule was superior to the OD schedule in controlling emesis in cancer chemotherapy, although this difference was not statistically significant.

Topics: Acute Disease; Adult; Antiemetics; Antineoplastic Agents; Cross-Over Studies; Dexamethasone; Drug Therapy, Combination; Female; Head and Neck Neoplasms; Humans; Isoquinolines; Male; Middle Aged; Nausea; Ondansetron; Palonosetron; Quinuclidines; Serotonin Antagonists; Time Factors; Vomiting

Aim of the present phase II non-randomized study was to verify whether palonosetron might be able to prevent acute and especially delayed CINV for either HEC or MEC, starting from the second chemotherapy cycle, in patients who had failed to respond to a different antiemetic 5-HT(3) antagonist during the first cycle. Stratification factor was age <65 years vs. > or =65 years of patients included. Forty-seven cancer patients (23 elderly and 24 non-elderly) scheduled to receive HEC or MEC regimens who had experienced CINV grade 3-4 during the first chemotherapy course and for whom the same course of chemotherapy regimen was further scheduled were enrolled. Complete response (CR) and complete control (CC) rates for the acute, delayed and overall phases of CINV were not significantly different between elderly and non-elderly patients. Palonosetron was safe: only grade 1-2 toxicities were observed with a peak of 12.9% for asthenia with no significant difference between elderly and non-elderly patients. In conclusion, single dose palonosetron (250 microg) should be considered a safe and effective second generation 5-HT(3) antagonist in the prevention of nausea and vomiting induced by HEC or MEC, irrespective of patients' age.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Dexamethasone; Female; Humans; Isoquinolines; Male; Middle Aged; Nausea; Neoplasms; Palonosetron; Quinuclidines; Serotonin Antagonists; Vomiting

The combination of palonosetron and aprepitant is safe and effective in the prevention of chemotherapy-induced emesis (CIE). The purpose of this pilot study was to ascertain the effectiveness of 1-day versus 3-day aprepitant in the prevention of acute and delayed nausea and vomiting in patients who were receiving highly emetogenic chemotherapy.. This study was institutional review board-approved and informed consent was obtained before this study was begun. This was a pilot, single-institution, randomized, double-blind, placebo-controlled trial that evaluated 3 different treatment arms. All groups received palonosetron 0.25 mg intravenously on Day 1 and dexamethasone on Days 1-4. Arm A received aprepitant 125 mg orally on Day 1 followed by 80 mg on Days 2-3. Arm B received aprepitant 125 mg orally on Day 1 and placebo on Days 2-3. Arm C received placebos on Days 1-3. The primary endpoint was to evaluate the proportion of patients with acute and delayed emesis within each group.. Seventy-five patients were included in the analysis. The study commenced with 3 groups; however, an interim analysis displayed unacceptable emesis events in Arm C, and this group was terminated. There were no significant differences between Arms A and B for emesis, nausea, or the use of breakthrough antiemetics. In Arms A and B, 93% of patients were emesis-free from Days 1-5 compared with only 50% in Arm C.. From this pilot study of patients who were receiving palonosetron, aprepitant, and dexamethasone for highly emetogenic chemotherapy, a single dose of aprepitant displayed similar effectiveness compared with 3-day aprepitant.

Topics: Acute Disease; Antiemetics; Antineoplastic Agents; Aprepitant; Dexamethasone; Double-Blind Method; Drug Therapy, Combination; Humans; Isoquinolines; Morpholines; Nausea; Palonosetron; Pilot Projects; Quinuclidines; Vomiting