Palonosetron plus dexamethasone for prevention of chemotherapy-induced nausea and vomiting in patients receiving multiple-day cisplatin chemotherapy for germ cell cancer.
OBJECTIVE
The aims of this study were to assess the safety and antiemetic efficacy of multiple-day dosing of palonosetron plus dexamethasone in patients receiving highly emetogenic multiple-day cisplatin-based chemotherapy for germ cell tumors.


METHODS
Forty-one men undergoing 5-day cisplatin-based chemotherapy for testicular cancer received palonosetron 0.25 mg IV once daily 30 min before chemotherapy on days 1, 3, and 5 plus IV dexamethasone 20 mg before chemotherapy on days 1 and 2, and 8 mg PO bid on days 6 and 7 and 4 mg bid on day 8. Safety and efficacy were assessed in 24-h intervals for 9 days. Efficacy endpoints included emesis, intensity of nausea and its interference with patient functioning, and rescue antiemetic use. A subset of patients (n = 11) was studied for electrocardiograph effects and pharmacokinetic evaluation.


RESULTS
This multiple-day antiemetic regimen was safe, with headache and constipation the most common treatment-related adverse events, mostly mild. Neither adverse events nor electrocardiographic changes appeared to increase in frequency, duration, or intensity over time despite a 1.42-fold systemic accumulation of palonosetron with repeated doses. The majority of patients had no emesis at any time throughout days 1-5 (51%) or days 6-9 (83%), had no moderate-to-severe nausea, and did not require rescue medication. Most patients reported that nausea had no significant effect on daily functioning on days 1-4 (72%) and days 5-9 (85%).


CONCLUSIONS
Palonosetron on days 1, 3, and 5, along with a regimen of dexamethasone, was safe and well tolerated and effectively controlled both nausea and emesis in patients undergoing 5-day cisplatin-based chemotherapy for testicular cancer.
Einhorn
Lawrence H
LH
Division of Hematology-Oncology, Indiana University School of Medicine, Indiana University Cancer Center, 535 Barnhill Drive, Room 473, Indianapolis, IN, 46202-5289, USA. leinhorn@iupui.edu.|Lance Armstrong Foundation, P.O. Box 161150, Austin, TX, 78716-1150, USA. leinhorn@iupui.edu.
Brames
Mary J
MJ
Division of Hematology-Oncology, Indiana University School of Medicine, Indiana University Cancer Center, 535 Barnhill Drive, Room 473, Indianapolis, IN, 46202-5289, USA.
Dreicer
Robert
R
Department of Solid Tumor Oncology, Taussig Cancer Center, The Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.
Nichols
Craig R
CR
Oregon Health and Science University, OHSU Cancer Institute, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA.
Cullen
Michael T
MT
MGI PHARMA, INC., 5775 W. Old Shakopee Road, Bloomington, MN, 55437, USA.
Bubalo
Joseph
J
Oregon Health and Science University, OHSU Cancer Institute, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA.
D000328:Adult; D000932:Antiemetics / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D003907:Dexamethasone / Q000494:pharmacology / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009325:Nausea / Q000139:chemically induced / Q000517:prevention & control*; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy*; D000077924:Palonosetron; D011812:Quinuclidines / Q000494:pharmacology / Q000627:therapeutic use*; D014481:United States; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*
D000932:Antiemetics; D000970:Antineoplastic Agents; D007546:Isoquinolines; D011812:Quinuclidines; D000077924:Palonosetron; D003907:Dexamethasone; D002945:Cisplatin