palonosetron and Multiple-Myeloma

Chemotherapy-induced nausea and vomiting (CINV) is a significant side effect in multiple myeloma (MM) patients receiving high-dose melphalan treatment followed by autologous stem cell transplantation (ASCT). We evaluated the efficacy and safety of a triple antiemetic combination of palonosetron, aprepitant, and low-dose dexamethasone in 24 MM patients who received melphalan conditioning (100 mg/m

Topics: Adult; Aged; Antiemetics; Aprepitant; Dexamethasone; Drug Therapy, Combination; Humans; Isoquinolines; Melphalan; Middle Aged; Morpholines; Multiple Myeloma; Myeloablative Agonists; Palonosetron; Postoperative Nausea and Vomiting; Quinuclidines; Transplantation, Autologous; Treatment Outcome

Explore safety and efficacy of three palonosetron-containing regimens for emesis prevention over 7 days in multiple myeloma (MM) patients receiving melphalan (100 mg/m(2)) and hematopoietic stem cell transplantation (HSCT).. Randomized, double-blind pilot study in MM patients (n=73) receiving 1, 2, or 3 days of 0.25 mg palonosetron (30-s i.v. bolus) 30 min before melphalan (days -2 and -1) and HSCT (day 0). Patients received dexamethasone (20 mg i.v., days -2 and -1) immediately before or after study drug/placebo. Daily diaries recorded emesis, rescue medication, nausea duration, and adverse events (AEs).. Seven-day complete protection (no emesis) occurred in 41.7% [95% confidence interval (CI) 22.1% to 63.4%], 41.7% (95% CI 22.1% to 63.4%), and 44.0% (95% CI 24.2% to 65.1%) of patients receiving 1, 2, or 3 days of palonosetron, respectively (P=0.43). Complete response (emesis free without rescue medication) occurred in 8.3%, 20.8%, and 20.0% (P=0.14). Common AEs (≥10%) were mild-to-moderate diarrhea, constipation, headache, insomnia, and flatulence. No serious AEs occurred.. Palonosetron with dexamethasone was safe and effective in preventing emesis in MM patients receiving melphalan and HSCT. This pilot study with a limited number of patients suggests that multiple doses of palonosetron could be more effective than a single dose in making patients emesis free without need for rescue medication. However, even multiple doses of palonosetron resulted in only 20% of patients being emesis free without rescue medication, suggesting that further improvement will require development of more effective combination antiemetic therapy.

Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Dexamethasone; Double-Blind Method; Female; Hematopoietic Stem Cell Transplantation; Humans; Isoquinolines; Male; Melphalan; Middle Aged; Multiple Myeloma; Nausea; Palonosetron; Quinuclidines; Vomiting

Chemotherapy-induced nausea and vomiting (CINV) is one of the most frequent adverse events compromising quality of life (QoL) in patients undergoing autologous stem cell transplantation (ASCT). However, CINV prophylaxis is still lacking uniformity for high-dose melphalan (HDM), which is used to condition patients with multiple myeloma (MM). Netupitant/palonosetron (NEPA) is administered with dexamethasone (DEXA) for CINV prevention in several chemotherapy regimens. Our study aims to assess the efficacy of NEPA, without DEXA, in preventing CINV in 106 adult patients with MM receiving HDM and ASCT. All patients had antiemetic prophylaxis with multiple doses of NEPA 1 h before the start of conditioning and after 72 h and 120 h. A complete response (CR) was observed in 99 (93%) patients at 120 h (overall phase). The percentage of patients with complete control was 93%. The CR rate during the acute phase was 94% (n = 100). During the delayed phase, the CR rate was 95% (n = 101). Grade 1 nausea and vomiting were experienced by 82% and 12% of the patients, respectively. Grade 2 nausea was reported in 18% and vomiting in 10% of patients. Our results showed, for the first time, that NEPA, without DEXA, was a well-tolerated and effective antiemetic option for MM patients receiving HDM followed by ASCT.

Topics: Antiemetics; Dexamethasone; Hematopoietic Stem Cell Transplantation; Humans; Melphalan; Multiple Myeloma; Nausea; Palonosetron; Pyridines; Quality of Life; Quinuclidines; Transplantation, Autologous; Vomiting

Topics: Adult; Aged; Antiemetics; Dexamethasone; Drug Therapy, Combination; Female; Hematopoietic Stem Cell Transplantation; Humans; Induction Chemotherapy; Male; Melphalan; Middle Aged; Multiple Myeloma; Nausea; Palonosetron; Prospective Studies; Pyridines; Transplantation Conditioning; Transplantation, Autologous; Vomiting

The current standard for prevention of chemotherapy-induced nausea/vomiting in autologous stem cell transplant only achieves 4-20% emetic control.. To assess emetic responses to multiday palonosetron, aprepitant, and low-dose dexamethasone among patients with myeloma and lymphoma undergoing autologous hematopoietic stem cell transplant.. Oral aprepitant 125/80/80 mg was administered with intravenous dexamethasone 4 mg and palonosetron 0.25 mg on days -3, -2, -1 for multiple myeloma and days -7 through -3 for lymphoma. Palonosetron was repeated day +3 in both groups.. A total of 20 patients were enrolled and 18 analyzed. None experienced emetic failure with complete control achieved in 78, 33, and 17% in the acute, delayed, and extended phases, respectively. Nausea occurred in 78% although not significant in 61%, with median Nausea Visual Score of 4.5. Quality of life correlated with emetic and nausea control. Eight patients developed grade 2-3 nonhematologic toxicities with only one event attributed to the study medications.. This triplet regimen was feasible with acceptable safety profile in the autologous hematopoietic stem cell transplant setting. Emetic control was best achieved in the acute phase. Lesser degree of emetic and nausea control in the delayed and extended phases impacted quality of life. Our results warrant further evaluation in a larger autologous hematopoietic stem cell transplant population.

Topics: Adult; Aged; Antiemetics; Aprepitant; Dexamethasone; Female; Hematopoietic Stem Cell Transplantation; Humans; Isoquinolines; Lymphoma; Male; Middle Aged; Morpholines; Multiple Myeloma; Nausea; Palonosetron; Pilot Projects; Quality of Life; Quinuclidines; Transplantation, Autologous; Vomiting