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Results of a 7-day aprepitant schedule for the prevention of nausea and vomiting in 5-day cisplatin-based germ cell tumor chemotherapy

Supportive Care in Cancer volume 21, pages 1561–1568 (2013)Cite this article

Abstract

Purpose

The purpose of this study was to determine the efficacy of adding a 7-day aprepitant schedule to a 5HT3 receptor antagonist and dexamethasone for patients with germ cell tumors receiving first-line 5-day cisplatin-based chemotherapy.

Methods

In a single-arm, open-label, multi-center, phase 2 trial, chemo-naive patients received aprepitant 125 mg PO (per oral) on day 1 and 80 mg PO on days 2 to 7, a 5HT3 receptor antagonist on days 1 to 5, and dexamethasone 8 mg on days 1 to 8. The primary endpoint was no emesis (vomiting or dry retching) during days 1 to 7 of cycle 1.

Results

Fifty patients were recruited. For cycle 1, proportions reporting no emesis on day 1, no emesis on days 1 to 7, no nausea on day 1, and no nausea on days 1 to 7 were 96, 82, 71, and 27 %, respectively. The efficacy was maintained in all cycles with over 80 % of patients reporting no emesis on any given day of any given cycle. Emesis was more common on days 4 to 7 (68 % episodes) than on days 1 to 3 (32 % episodes). Over any 24-h period, 49 % of patients with emesis reported no more than two episodes, and 62 % of patients with nausea reported intensity as 3 or less on a scale from 0 to 10. There were no unexpected or serious adverse events reported.

Conclusion

Adding 7 days of aprepitant to a 5HT3 receptor antagonist and dexamethasone effectively controlled acute and delayed emesis with 5-day cisplatin regimens. Days of nausea were more common than days of vomiting.

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References

  1. Grimison PS, Stockler MR, Thomson DB, Olver IN, Harvey VJ, Gebski VJ, Lewis CR, Levi JA, Boyer MJ, Gurney H, Craft P, Boland AL, Simes RJ, Toner GC (2010) Comparison of two standard chemotherapy regimens for good-prognosis germ cell tumors: updated analysis of a randomized trial. J Natl Cancer Inst 102:1–10

    Article  Google Scholar 

  2. Einhorn LH, Brames MJ, Dreicer R, Nichols CR, Cullen MT Jr, Bubalo J (2007) 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 15:1293–130

    PubMed  Article  Google Scholar 

  3. Kris MG, Hesketh PJ, Herrstedt J, Rittenberg C, Einhorn LH, Grunberg S, Koeller J, Olver I, Borjeson S, Ballatori E (2005) Consensus proposals for the prevention of acute and delayed vomiting and nausea following high-emetic-risk chemotherapy. Support Care Cancer 13:85–96

    PubMed  Article  Google Scholar 

  4. Einhorn LH, Grunberg SM, Rapoport B, Rittenberg C, Feyer P (2011) Antiemetic therapy for multiple-day chemotherapy and additional topics consisting of rescue antiemetics and high-dose chemotherapy with stem cell transplant review and consensus statement. Supportive Care in Cancer 19(Suppl 1):S1–S4

    PubMed  Article  Google Scholar 

  5. Roila F, Herrstedt J, Aapro M, Gralla RJ, Einhorn LH, Ballatori E, Bria E, Cark-Snow RA, Esperson BT, Feyer P, Grunberg SM, Hesketh PJ, Jordan K, Kris MJ, Maranzano E, Molassiotis A, Morrow G, Olver I, Rapoport BL, Rittenberg C, Saito M, Tonato M, Warr D; ESMO/MASCC Guidelines Working Group (2010) Guideline update for MASCC and ESMO in the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting: results of the Perugia consensus conference. Ann Oncol 21(suppl 5):232–243

    Google Scholar 

  6. Toner GC, Stockler MR, Boyer MJ, Jones M, Thomson DB, Harvey VJ, Olver IN, Dhillon H, McMullen A, Gebski VJ, Levi JA, Simes RJ (2001) Comparison of two standard chemotherapy regimens for good-prognosis germ-cell tumours: a randomized trial. Australian and New Zealand Germ Cell Trial Group. Lancet 357(9258):739–45

    PubMed  Article  CAS  Google Scholar 

  7. Tattersall FD, Rycroft W, Francis B, Pearce D, Merchant K, MacLoed AM, Ladduwahetty T, Keown L, Swain C, Baker R, Cascieri M, Ber E, Metzger J, MacIntyre DE, Hill RG, Hargreaves RJ (1996) Tachykinin NK1 receptor antagonists act centrally to inhibit emesis induced by the chemotherapeutic agent cisplatin in ferrets. Neuropharmacology 35:1121–1129

    PubMed  Article  CAS  Google Scholar 

  8. Poli-Bigelli S, Rodrigues-Pereira J, Carides AD, Juie Ma G, Eldridge K, Hipple A, Evans JK, Horgan KJ, Lawson F; Aprepitant Protocol 054 Study Group (2003) Addition of the neurokinin 1 receptor antagonist aprepitant to standard antiemetic therapy improves control of chemotherapy-induced nausea and vomiting. Cancer 97:3090–3098

    Article  Google Scholar 

  9. Hesketh PJ, Grunberg SM, Gralla RJ, Warr DG, Roila F, De Wit R, Chawla SP, Carides AD, Ianus J, Elmer ME, Evans JK, Beck K, Reines S, Horgan KJ, Aprepitant Protocoll 052 Study Group (2003) The oral neurokinin-1 antagonist aprepitant for the prevention of chemotherapy-induced nausea and vomiting: a multinational, randomized, double-blind, placebo-controlled trial in patients receiving high-dose cisplatin—the Aprepitant Protocol 052 Study Group. J Clin Oncol 21:4112–4119

    PubMed  Article  CAS  Google Scholar 

  10. Chawla SP, Grunberg SM, Gralla RJ, Hesketh PJ, Rittenberg C, Elmer ME, Scmidt C, Taylor A, Carides AD, Evans JK, Horgan JK (2003) Establishing the dose of the oral NK1 antagonist aprepitant for the prevention of chemotherapy-induced nausea and vomiting. Cancer 97:2290–2300

    PubMed  Article  CAS  Google Scholar 

  11. McRea JB, Majumbar AK, Goldberg MR, Goldberg MR, Iwamato M, Gargano C, Panebianco DL, Hesny M, Lines CR, Petty KJ, Deutsch PJ, Murphy MG, Gottesdiener KM, Goldwater DR, Blum RA (2003) Effects of the neurokinin 1 receptor antagonist aprepitant on the pharmacokinetics of dexamethasone and methylprednisolone. Clin Pharmacol Ther 74:17–24

    Article  Google Scholar 

  12. Grimison PS, Thomson DB, Stockler MR, et al. (2011) Accelerated BEP for advanced germ cell tumours: an Australian multicenter phase I/II trial. J Clin Oncol 29 (Suppl; abstr 4561)

  13. Herrstedt J, Muss HB, Warr DG, Hesketh PJ, Eisenberg PD, Raftopoulos H, Grunberg SM, Gabriel M, Rodgers A, Hustad CM, Horgan KJ, Skobieranda F, Aprepitant Moderately Emetogenic Chemotherapy Study Group (2005) Efficacy and tolerability of aprepitant for the prevention of chemotherapy-induced nausea and emesis over multiple cycles of moderately emetogenic chemotherapy. Cancer 104:1548–1555

    PubMed  Article  CAS  Google Scholar 

  14. Einhorn L, Brames M, Dreicer R, Nichols CR, Cullen MT Jr (2007) Palonosetron plus dexamethasone for prevention of chemotherapy-induced nausea and vomiting in patients receiving multiple-day cisplatin chemotherapy for germ cell cancer. Supportive Care in Cancer 15(11):1293–300

    PubMed  Article  Google Scholar 

  15. Jordan K, Kinitz I, Voigt W, Behlendorf T, Wolf H-H, Schmoll H-J (2009) Safety and efficacy of a triple antiemetic combination with the the NK-1 antagonist aprepitant in highly and moderately emetogenic multiple-day chemotherapy. Eur J Cancer 45:1184–1187

    PubMed  Article  CAS  Google Scholar 

  16. Molassiotis A, Stricker CT, Eaby B, Velders L, Coventary PA (2008) Understanding the concept of chemotherapy-related nausea: the patient experience. Eur J Cancer Care (Engl) 17:444–453

    Article  CAS  Google Scholar 

  17. D’Acquisto RW, Tyson LB, Gralla RJ et al (1986) The influence of a chronic high alcohol intake on chemotherapy-induced nausea and vomiting. Proc Am Soc Clin Oncol 5:257

    Google Scholar 

  18. Albany C, Brames MJ, Fausel C, Johnson CS, Picus J, Einhorn LH (2012) Randomized, double-blind, placebo-controlled, phase III cross-over study evaluating the oral neurokinin-1 antagonist aprepitant in combination with a 5HT3 receptor antagonist and dexamethasone in patients with germ cell tumors receiving 5-day cisplatin combination chemotherapy regimens: a Hoosier Oncology Group Study. J Clin Oncol 30:3998–4003

    PubMed  Article  CAS  Google Scholar 

  19. Hesketh PJ, Wright O, Rosati G, Russo M, Levin J, Lane S, Moiseyenko V, Dube P, Kopp M, Makhson A (2011) Single-dose intravenous casopitant in combination with ondansetron and dexamethasone for the prevention of oxaliplatin-induced nausea and vomiting: a multicentre, randomized, double-blind, active-controlled, two arm parallel group study. Support Care Cancer 20:1471–1478

    PubMed  Article  Google Scholar 

  20. Olver IN (2008) Prevention of chemotherapy-induced nausea and vomiting: focus on fosaprepitant. Ther Clin Risk Manag 4:1–6

    Google Scholar 

Download references

Acknowledgments

The authors acknowledge the contributions of the patients and the investigators. This study was conducted under the auspices of ANZUP and coordinated by the National Health and Medical Research Council Clinical Trials Centre, University of Sydney. It was supported in part by drug supply from Investigator-Initiated Studies Program of Merck and Co. and research grant from Merck Sharp & Dohme (Australia) Pty Limited. IDD is supported by an NHMRC Practitioner Fellowship. The opinions expressed in this paper are those of the authors and do not necessarily represent those of Merck & Co or Merck Sharpe & Dohme (Australia) Pty Limited.

Conflict of interest

Two of the authors, Ian Olver and Martin Stockler, applied for and received a grant from Merck Sharp & Dohme (Australia) Pty Limited to partly fund this study but have no other relationship with this company to declare. None of the authors have other conflicts of interest to declare. The authors had full control of the primary data and agree to allow the journal to review those data if requested.

Author information

Affiliations

  1. Sydney Medical School, CEO Cancer Council Australia, GPO Box 408, Sydney, New South Wales, 2001, Australia

    I. N. Olver

  2. Sydney Cancer Centre, Sydney, New South Wales, Australia

    P. Grimison & M. R. Stockler

  3. NHMRC Clinical Trials Centre, University of Sydney, Sydney, New South Wales, Australia

    M. Chatfield, M. R. Stockler, V. Gebski, A. Boland & A. McDonald

  4. Peter MacCallum Cancer Centre, East Melbourne and University of Melbourne, Melbourne, Australia

    G. C. Toner

  5. Royal Hobart Hospital, Hobart, Tasmania, Australia

    R. Harrup

  6. Border Medical Oncology, Albury, Victoria, Australia

    C. Underhill

  7. Flinders Medical Centre, Flinders University, Adelaide, South Australia, Australia

    G. Kichenadasse

  8. Royal Adelaide Hospital, Adelaide, South Australia, Australia

    N. Singhal

  9. Ludwig Institute for Cancer Research, Austin Health, Melbourne, Victoria, Australia

    I. D. Davis

  10. Princess Alexandra Hospital, Brisbane, Queensland, Australia

    D. Thomson

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  1. I. N. Olver
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  2. P. Grimison
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  3. M. Chatfield
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  4. M. R. Stockler
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  5. G. C. Toner
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  6. V. Gebski
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  7. R. Harrup
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  8. C. Underhill
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  9. G. Kichenadasse
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  10. N. Singhal
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  11. I. D. Davis
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  12. A. Boland
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  13. A. McDonald
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  14. D. Thomson
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for the Australian and New Zealand Urogenital and Prostate Cancer Trials Group

Corresponding author

Correspondence to I. N. Olver.

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Olver, I.N., Grimison, P., Chatfield, M. et al. Results of a 7-day aprepitant schedule for the prevention of nausea and vomiting in 5-day cisplatin-based germ cell tumor chemotherapy. Support Care Cancer 21, 1561–1568 (2013). https://doi.org/10.1007/s00520-012-1696-0

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Keywords

  • Aprepitant
  • Dexamethasone
  • 5Hydroxytryptamine3 receptor antagonist
  • 5-day cisplatin
  • Antiemetic
  • Germ cell tumors