Pooled analysis of phase III clinical studies of palonosetron versus ondansetron, dolasetron, and granisetron in the prevention of chemotherapy-induced nausea and vomiting (CINV)

Abstract

PurposePreventing chemotherapy-induced nausea and vomiting (CINV) is integral to treatment success in patients with cancer. This analysis was undertaken to assess the relative efficacy and safety of palonosetron versus older 5HT3 RAs in preventing CINV associated with moderately or highly emetogenic chemotherapy.MethodsPatient-level data from four randomized, double-blind, phase III trials comparing palonosetron 0.25 or 0.75 mg with ondansetron 32 mg, dolasetron 100 mg, or granisetron 40 μg/kg were analyzed. Endpoints included complete response (CR: no emesis and no rescue antiemetics) in the acute (0–24 h), delayed (>24–120 h), and overall (0–120 h) postchemotherapy periods (primary), complete control (CC: no emesis, no rescue antiemetics, and no more than mild nausea), number of emetic episodes, and nausea severity.ResultsCR rates were significantly higher for palonosetron (n = 1,787) versus older 5HT3 RAs (n = 1,175) in the delayed (57 vs 45 %, P < 0.0001) and overall periods (51 vs 40 %, P < 0.0001); odds ratios (95 % CI) in the acute, delayed, and overall periods were 1.15 (0.98–1.34), 1.62 (1.40–1.88), and 1.56 (1.34–1.81), respectively. Significant differences in CC rates and nausea severity were observed for the delayed and overall periods and in emetic episodes for all three periods. The incidence of treatment-related adverse events was similar with palonosetron (0.25 mg, 20.0 %; 0.75 mg, 26.5 %) and older 5HT3 RAs (27.5 %).ConclusionsPalonosetron is more effective than older 5HT3 RAs for controlling CINV in the delayed and overall postchemotherapy periods.

Synthesis and evaluation of (S)-[18F]fesetron in the rat brain as a potential PET imaging agent for serotonin 5-HT3 receptors

“…28 The CINV drugs are known to mediate their effects by acting on this region in the brain and brain stem. 1,29 Further confirmation of this brain region will have to be carried out.…”

Comparative investigation of the anti-emetic effects of granisetron and palonosetron during the treatment of acute myeloid leukemia

“…Several investigators reported that palonosetron provides more effective CINV control through the entire chemotherapy process (including the delayed phase) than any other 5-HT3 receptor to date (16,17). The present results similarly observed that palonosetron is effective for controlling acute-and delayed-phase nausea through the entire treatment period.…”

Palonosetron for the treatment of chemotherapy-induced nausea and vomiting

“…concluded that palonosetron was more effective than the first-generation receptor antagonists in preventing acute and delayed CINV in patients receiving MEC or HEC, regardless of the use of concomitant corticosteroids. Schwartzberg et al [47] concluded that palonosetron is more effective than the first-generation 5-HT 3 receptor antagonists in controlling CINV in the delayed and overall post-chemotherapy periods based on a pooled analysis of Phase III clinical studies of palonosetron versus ondansetron, dolasetron, and granisetron. In an additional review, Popovic et al [48] concluded that palonosetron is safer and more efficacious than the other 5-HT 3 receptor antagonists.…”

“…The adverse reactions reported were the most common reactions reported for the 5-HT 3 receptor antagonist class, headache, and constipation. All other reactions occurred at an incidence of £ 1% in patients treated with 0.25 mg of palonosetron [44][45][46][47][48][49][50].…”