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Palonosetron plus dexamethasone for prevention of chemotherapy-induced nausea and vomiting in patients receiving multiple-day cisplatin chemotherapy for germ cell cancer

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Abstract

Goals of work

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.

Materials and 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.

Main 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.

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Notes

  1. Kytril® (2005) (granisetron hydrochloride) Injection. Prescribing information. Roche Laboratories, Inc. Nutley, NJ, USA November 2005.

  2. Zofran® (2006) (ondansetron hydrochloride) Injection. Prescribing information. GlaxoSmithKline, Research Triangle Park, NC, USA. February 2006.

  3. Anzemet® (2006) Injection (dolasetron meselate injection). Prescribing information. Sanofi-Aventis US, L.L.C., Bridgewater, NJ, USA, June 2006.

  4. Aloxi® (palonosetron HCl) injection. Prescribing information. Helsinn Birex Pharmaceuticals Ltd., Damastown, Dublin, Republic of Ireland: 2005; MGI PHARMA, INC., Bloomington, MN, USA, January 2006.

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Acknowledgments

This research was sponsored by Helsinn Healthcare, S.A., Pambio-Noranco (Lugano), Switzerland and supported by MGI PHARMA, INC., Bloomington, MN, USA. Bruce Roth, MD, from Vanderbilt Medical Center, Nashville, TN, USA contributed to this research as a principal investigator. Medical writing and editorial assistance in the preparation of this manuscript were provided by Thomson Scientific Connexions through support from MGI PHARMA, INC. Portions of this research have been presented in poster form at the 42nd Annual Meeting of the American Society of Clinical Oncology, June 2–6, 2006, Atlanta, GA, USA; at the 2006 MASCC/ISOO18th International Symposium, June 22–24, 2006, Toronto, Canada; and at the 2nd Annual Chicago Supportive Oncology Conference, September 28–30, 2006, Chicago, IL, USA.

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Authors and Affiliations

  1. Division of Hematology–Oncology, Indiana University School of Medicine, Indiana University Cancer Center, 535 Barnhill Drive, Room 473, Indianapolis, IN, 46202-5289, USA

    Lawrence H. Einhorn & Mary J. Brames

  2. Lance Armstrong Foundation, P.O. Box 161150, Austin, TX, 78716-1150, USA

    Lawrence H. Einhorn

  3. Department of Solid Tumor Oncology, Taussig Cancer Center, The Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA

    Robert Dreicer

  4. Oregon Health and Science University, OHSU Cancer Institute, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA

    Craig R. Nichols & Joseph Bubalo

  5. MGI PHARMA, INC., 5775 W. Old Shakopee Road, Bloomington, MN, 55437, USA

    Michael T. Cullen Jr.

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  1. Lawrence H. Einhorn
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  2. Mary J. Brames
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  3. Robert Dreicer
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  5. Michael T. Cullen Jr.
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Correspondence to Lawrence H. Einhorn.

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Einhorn, L.H., Brames, M.J., Dreicer, R. et al. Palonosetron plus dexamethasone for prevention of chemotherapy-induced nausea and vomiting in patients receiving multiple-day cisplatin chemotherapy for germ cell cancer. Support Care Cancer 15, 1293–1300 (2007). https://doi.org/10.1007/s00520-007-0255-6

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