Medline ® Abstracts for References 38-40
of 'Prevention and treatment of chemotherapy-induced nausea and vomiting in adults'
Improved prevention of moderately emetogenic chemotherapy-induced nausea and vomiting with palonosetron, a pharmacologically novel 5-HT3 receptor antagonist: results of a phase III, single-dose trial versus dolasetron.
Eisenberg P, Figueroa-Vadillo J, Zamora R, Charu V, Hajdenberg J, Cartmell A, Macciocchi A, Grunberg S, 99-04 Palonosetron Study Group
BACKGROUND: Palonosetron, a highly selective and potent 5-HT(3) receptor antagonist with a strong binding affinity and a long plasma elimination half-life (approximately 40 hours), has shown efficacy in Phase II trials in preventing chemotherapy-induced nausea and vomiting (CINV) resulting from highly emetogenic chemotherapy. The current Phase III trial evaluated the efficacy and safety of palonosetron in preventing acute and delayed CINV after moderately emetogenic chemotherapy.
METHODS: In the current study, 592 patients were randomized to receive a single, intravenous dose of palonosetron 0.25 mg, palonosetron 0.75 mg, or dolasetron 100 mg, 30 minutes before receiving moderately emetogenic chemotherapy. The primary efficacy endpoint was the proportion of patients with a complete response (CR; defined as no emetic episodes and no rescue medication) during the first 24 hours after chemotherapy. Secondary endpoints included assessment of prevention of delayed emesis (2-5 days postchemotherapy).
RESULTS: In the current study, 569 patients received study medication and were included in the intent-to-treat efficacy analyses. CR rates during the first 24 hours were 63.0% for palonosetron 0.25 mg, 57.1% for palonosetron 0.75 mg, and 52.9% for dolasetron 100 mg. CR rates during the delayed period (24-120 hours after chemotherapy) were superior for palonosetron compared with dolasetron. Adverse events (AEs) were mostly mild to moderate and not related to study medication, with similar incidences among groups. There were no serious drug-related AEs.
CONCLUSIONS: A single dose of palonosetron is as effective as a single dose of dolasetron in preventing acute CINV and superior to dolasetron in preventing delayed CINV after moderately emetogenic chemotherapy, with a comparable safety profile for all treatment groups.
California Cancer Care, Greenbrae, California, USA.
Palonosetron improves prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy: results of a double-blind randomized phase III trial comparing single doses of palonosetron with ondansetron.
Gralla R, Lichinitser M, Van Der Vegt S, Sleeboom H, Mezger J, Peschel C, Tonini G, Labianca R, Macciocchi A, Aapro M
Ann Oncol. 2003;14(10):1570.
BACKGROUND: Although all first-generation 5-HT(3) receptor antagonists demonstrate efficacy in preventing acute chemotherapy-induced nausea and vomiting (CINV), effective prevention of delayed CINV has not yet been achieved. This study compared the efficacy and tolerability of palonosetron, a novel, second-generation 5-HT(3) receptor antagonist, with ondansetron.
PATIENTS AND METHODS: In this multicenter, randomized, double-blind, stratified, phase III study, 570 adult cancer patients were randomized to receive a single i.v. dose of palonosetron 0.25 mg, palonosetron 0.75 mg or ondansetron 32 mg, each administered 30 min before initiation of moderately emetogenic chemotherapy. The primary end point was the proportion of patients with no emetic episodes and no rescue medication [complete response (CR)]during the 24 h after chemotherapy administration (acute period). Secondary end points included efficacy in treatment of delayed CINV (</=5 days post-chemotherapy) and overall tolerability.
RESULTS: 563 patients were evaluable for efficacy. CR rates were significantly higher (P<0.01) for palonosetron 0.25 mg than ondansetron during the acute (0-24 h) (81.0% versus 68.6%, respectively), delayed (24-120 h) (74.1% versus 55.1%) and overall (0-120 h) (69.3% versus 50.3%) periods. CR rates achieved with palonosetron 0.75 mg were numerically higher but not statistically different from ondansetron during all three time intervals. Both treatments were well tolerated.
CONCLUSIONS: A single i.v. dose of palonosetron 0.25 mg was significantly superior to i.v. ondansetron 32 mg in the prevention of acute and delayed CINV.
New York Lung Cancer Alliance, New York, NY, USA.
A systematic review and meta-analysis of intravenous palonosetron in the prevention of chemotherapy-induced nausea and vomiting in adults.
Likun Z, Xiang J, Yi B, Xin D, Tao ZL
Oncologist. 2011;16(2):207. Epub 2011 Jan 31.
OBJECTIVES: We performed a systematic review and meta-analysis to compare treatment effectiveness and adverse effects in cancer patients receiving chemotherapy with palonosetron to prevent chemotherapy-induced nausea and vomiting (CINV).
METHODS: We identified randomized controlled clinical trials (RCT) comparing palonosetron with first-generation 5-HT3RA in the prevention of CINV in cancer patients. Meta-analyses were performed on homogeneous studies. Fixed or random-effects models were used to combine data.
RESULTS: Eight eligible trials were identified, reporting outcomes on 3,592 patients. Meta-analyses showed statistically significant differences in favor of palonosetron compared with first-generation 5-HT3RA in prevention of acute CINV (p = .0003), delayed CINV (p<.00001), and overall phase of CINV (p<.00001). Subgroup analyses showed statistically significant differences in favor of both 0.25 mg and 0.75 mg of palonosetron in prevention of all phases of CINV. There were no statisticallysignificant differences between 0.25 and 0.75 mg of palonosetron. Compared with the first-generation 5-HT3RA, 0.75 mg of palonosetron showed a statistically significant difference in the occurrence of constipation (p = .04).
INTERPRETATION: The use of palonosetron should be considered an integral part of adjuvant therapy for prevention of the acute, delayed, and overall phases of CINV. The 0.25 mg intravenous palonosetron dose is as effective as the 0.75 mg intravenous palonosetron dose. However, 0.75 mg intravenous palonosetron causes constipation more frequently than the first-generation 5-HT3RA.
Digestive Oncology Department of Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China. firstname.lastname@example.org