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Differential time course of action of 5-HT3 and NK1 receptor antagonists when used with highly and moderately emetogenic chemotherapy (HEC and MEC)

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Abstract

Background

Cisplatin-based highly emetogenic chemotherapy (HEC) displays a biphasic pattern of emesis with both an early and delayed period. In contrast, moderately emetogenic chemotherapy (MEC) has a monophasic pattern. The objective of this analysis was to further investigate the impact of the NK1-receptor antagonist aprepitant on these patterns.

Methods

Three phase III HEC (patients scheduled to receive cisplatin-based chemotherapy) and one phase III MEC (breast cancer patients scheduled to receive anthracycline plus cyclophosphamide (AC)) trials of aprepitant were included. In all studies, patients were randomized in a 1:1 ratio to an aprepitant regimen (aprepitant plus ondansetron plus dexamethasone) or the standard regimen (ondansetron plus dexamethasone). The exact dosing regimen for ondansetron and dexamethasone was different in each study. In a post hoc analysis, multivariate logistic regression models were used to assess the impact on first emesis at different time intervals after chemotherapy.

Results

One thousand five hundred twenty-seven patients and 856 patients were randomized and assessed for efficacy in the HEC and MEC trials, respectively. For HEC, aprepitant reduced the risk of first emesis by 38–77% vs. standard regimen, beginning 15–18 h after cisplatin and extending to 60 h. For MEC, aprepitant reduced the risk of first emesis by 38–61% vs. active control, beginning 3 h after AC and for up to 12 h.

Conclusions

Time of onset and duration of enhanced control of emesis with the addition of aprepitant differed between HEC and MEC. This suggests that the pattern of NK1-sensitive mechanisms may vary for different chemotherapy regimens.

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References

  1. Sun CC, Bodurka DC, Weaver CB, Rasu R, Wolf JK, Bevers MW, Smith JA, Wharton JT, Rubenstein EB (2005) Rankings and symptom assessments of side effects from chemotherapy: insights from experienced patients with ovarian cancer. Support Care Cancer 13:219–227

    Article  PubMed  Google Scholar 

  2. Hesketh PJ (2008) Chemotherapy-induced nausea and vomiting. N Engl J Med 358:2482–2494

    Article  PubMed  CAS  Google Scholar 

  3. Roila F, Tonato M, Cognetti F, Cortesi E, Favalli G, Marangolo M, Amadori D, Bella MA, Gramazio V, Donati D et al (1991) Prevention of cisplatin-induced emesis: a double-blind multicenter randomized crossover study comparing ondansetron and ondansetron plus dexamethasone. J Clin Oncol 9:675–678

    PubMed  CAS  Google Scholar 

  4. Smith DB, Newlands ES, Rustin GJ, Begent RH, Howells N, McQuade B, Bagshawe KD (1991) Comparison of ondansetron and ondansetron plus dexamethasone as antiemetic prophylaxis during cisplatin-containing chemotherapy. Lancet 338:487–490

    Article  PubMed  CAS  Google Scholar 

  5. Hesketh PJ, Harvey WH, Harker WG, Beck TM, Ryan T, Bricker LJ, Kish JA, Murphy WK, Hainsworth JD, Haley B (1994) A randomized, double-blind comparison of intravenous ondansetron alone and in combination with intravenous dexamethasone in the prevention of high-dose cisplatin-induced emesis. J Clin Oncol 12:596–600

    PubMed  CAS  Google Scholar 

  6. Tavorath R, Hesketh PJ (1996) Drug treatment of chemotherapy-induced delayed emesis. Drugs 52:639–648

    Article  PubMed  CAS  Google Scholar 

  7. Tattersall FD, Rycroft W, Cumberbatch M, Mason G, Tye S, Williamson DJ, Hale JJ, Mills SG, Finke PE, MacCoss M, Sadowski S, Ber E, Cascieri M, Hill RG, MacIntyre DE, Hargreaves RJ (2000) The novel nk1 receptor antagonist mk-0869 (l-754, 030) and its water soluble phosphoryl prodrug, l-758, 298, inhibit acute and delayed cisplatin-induced emesis in ferrets. Neuropharmacology 39:652–663

    Article  PubMed  CAS  Google Scholar 

  8. Poli-Bigelli S, Rodrigues-Pereira J, Carides AD, Julie Ma G, Eldridge K, Hipple A, Evans JK, Horgan KJ, Lawson F (2003) Addition of the neurokinin 1 receptor antagonist aprepitant to standard antiemetic therapy improves control of chemotherapy-induced nausea and vomiting. Results from a randomized, double-blind, placebo-controlled trial in latin america. Cancer 97:3090–3098

    Article  PubMed  CAS  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 (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

    Article  PubMed  CAS  Google Scholar 

  10. Schmoll HJ, Aapro MS, Poli-Bigelli S, Kim HK, Park K, Jordan K, von Pawel J, Giezek H, Ahmed T, Chan CY (2006) Comparison of an aprepitant regimen with a multiple-day ondansetron regimen, both with dexamethasone, for antiemetic efficacy in high-dose cisplatin treatment. Ann Oncol 17:1000–1006

    Article  PubMed  CAS  Google Scholar 

  11. Hesketh PJ, Van Belle S, Aapro M, Tattersall FD, Naylor RJ, Hargreaves R, Carides AD, Evans JK, Horgan KJ (2003) Differential involvement of neurotransmitters through the time course of cisplatin-induced emesis as revealed by therapy with specific receptor antagonists. Eur J Cancer 39:1074–1080

    Article  PubMed  CAS  Google Scholar 

  12. Warr DG, Hesketh PJ, Gralla RJ, Muss HB, Herrstedt J, Eisenberg PD, Raftopoulos H, Grunberg SM, Gabriel M, Rodgers A, Bohidar N, Klinger G, Hustad CM, Horgan KJ, Skobieranda F (2005) Efficacy and tolerability of aprepitant for the prevention of chemotherapy-induced nausea and vomiting in patients with breast cancer after moderately emetogenic chemotherapy. J Clin Oncol 23:2822–2830

    Article  PubMed  CAS  Google Scholar 

  13. Martin M (1996) The severity and pattern of emesis following different cytotoxic agents. Oncology 53(Suppl 1):26–31

    Article  PubMed  Google Scholar 

  14. Roila F, Donati D, Tamberi S, Margutti G (2002) Delayed emesis: incidence, pattern, prognostic factors and optimal treatment. Support Care Cancer 10:88–95

    Article  PubMed  Google Scholar 

  15. Cocquyt V, Van Belle S, Reinhardt R et al (2001) L-758, 298, a prodrug for the selective neurokinin-1 antagonist, L-754, 030, compared to ondansetron for the prevention of cisplatin-induced emesis. Eur J Cancer 37:835–842

    Article  PubMed  CAS  Google Scholar 

  16. Campos D, Pereira JR, Reinhardt R et al (2001) Prevention of cisplatin-induced emesis by the oral neurokinin-1 antagonist, aprepitant, in combination with granisetron and dexamethasone or with dexamethasone alone. J Clin Oncol 19:1759–1767

    PubMed  CAS  Google Scholar 

  17. Hesketh PJ (1999) Defining the emetogenicity of cancer chemotherapy regimens: relevance to clinical practice. Oncologist 4:191–196

    PubMed  CAS  Google Scholar 

  18. Grunberg SM, Dugan M, Muss H, Wood M, Burdette-Radoux S, Weisberg T, Siebel M (2009) Effectiveness of a single-day three-drug regimen of dexamethasone, palonosetron, and aprepitant for the prevention of acute and delayed nausea and vomiting caused by moderately emetogenic chemotherapy. Support Care Cancer 17:589–594

    Article  PubMed  Google Scholar 

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Disclosures

PJH is a consultant to and has received honoraria from Merck & Co., and has received research funding from Merck & Co. and GlaxoSmithKline. DGW is a consultant to Merck & Co. JCS is a paid consultant to Merck & Co. ADC is an employee of Merck & Co.

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Authors and Affiliations

  1. Department of Hematology Oncology, Lahey Clinic Medical Center, 41 Mall Road, Burlington, MA, 01805, USA

    Paul J. Hesketh

  2. Princess Margaret Hospital, 610 University Avenue, Toronto, ON, M5G 2M9, Canada

    David G. Warr

  3. Reagent, 148 W24 Street #12, New York, NY, 10011, USA

    James C. Street

  4. Merck Research Laboratories, 351 N. Sumneytown Pike, North Wales, PA, 19154, USA

    Alexandra D. Carides

Authors
  1. Paul J. Hesketh
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  2. David G. Warr
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  3. James C. Street
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  4. Alexandra D. Carides
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Correspondence to Paul J. Hesketh.

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Reagent is a medical communications company under contract with Merck & Co., Inc.

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Hesketh, P.J., Warr, D.G., Street, J.C. et al. Differential time course of action of 5-HT3 and NK1 receptor antagonists when used with highly and moderately emetogenic chemotherapy (HEC and MEC). Support Care Cancer 19, 1297–1302 (2011). https://doi.org/10.1007/s00520-010-0944-4

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  • DOI: https://doi.org/10.1007/s00520-010-0944-4

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