Three palonosetron regimens to prevent CINV in myeloma patients receiving multiple-day high-dose melphalan and hematopoietic stem cell transplantation

Ann Oncol. 2011 Apr;22(4):939-946. doi: 10.1093/annonc/mdq457. Epub 2010 Oct 8.

Abstract

Background: 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).

Patients and methods: 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).

Results: 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.

Conclusions: 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Alkylating / administration & dosage
  • Antineoplastic Agents, Alkylating / adverse effects*
  • Antineoplastic Agents, Alkylating / therapeutic use
  • Dexamethasone / administration & dosage
  • Dexamethasone / adverse effects
  • Dexamethasone / therapeutic use
  • Double-Blind Method
  • Female
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Isoquinolines / administration & dosage
  • Isoquinolines / adverse effects
  • Isoquinolines / therapeutic use*
  • Male
  • Melphalan / administration & dosage
  • Melphalan / adverse effects*
  • Melphalan / therapeutic use
  • Middle Aged
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / surgery
  • Nausea / chemically induced
  • Nausea / prevention & control*
  • Palonosetron
  • Quinuclidines / administration & dosage
  • Quinuclidines / adverse effects
  • Quinuclidines / therapeutic use*
  • Vomiting / chemically induced
  • Vomiting / prevention & control*

Substances

  • Antineoplastic Agents, Alkylating
  • Isoquinolines
  • Quinuclidines
  • Palonosetron
  • Dexamethasone
  • Melphalan