Supportive Care in Cancer

, Volume 18, Issue 9, pp 1171–1177 | Cite as

Evaluation of risk factors predictive of nausea and vomiting with current standard-of-care antiemetic treatment: analysis of two phase III trials of aprepitant in patients receiving cisplatin-based chemotherapy

  • Paul J. HeskethEmail author
  • Matti Aapro
  • James C. Street
  • Alexandra D. Carides
Original Article


Goals of work

Certain patient and treatment characteristics are predictive of chemotherapy-induced nausea and vomiting (CINV). Objectives of this analysis were: (1) confirm the importance of several previously reported adverse risk factors for CINV in patients receiving chemotherapy, (2) assess the impact of the NK1 receptor antagonist aprepitant according to these risk factors, and (3) assess the impact of age on antiemetic outcome.

Patients and methods

Patients from two double-blind, placebo-controlled trials were randomized to an active-control group (ondansetron 32 mg IV, dexamethasone 20 mg PO day 1; dexamethasone 8 mg bid days 2–4) or an aprepitant group (aprepitant 125 mg PO, ondansetron 32 mg IV, dexamethasone 12 mg day 1; aprepitant 80 mg days 2–3; dexamethasone 8 mg qd days 2–4). The primary endpoint was complete response (no emesis or rescue therapy use). In a post-hoc analysis, multivariate logistic regression models were used to assess the impact of treatment with aprepitant and previously reported risk factors, using a modified intent-to-treat approach.

Main results

Treatment with aprepitant (p < 0.0001), male gender (p = 0.023), cisplatin dose <80 mg/m2 (p = 0.001), age ≥65 years (p = 0.021), and five or more alcoholic drinks per week (p = 0.027) were all significantly associated with improved complete response. Aprepitant improved complete response regardless of risk for all factors and neutralized the risk associated with female gender.


This analysis confirmed the relevance of several previously reported risk factors for CINV in patients receiving chemotherapy. Aprepitant improved complete response regardless of risk and eliminated the increased risk of CINV associated with the female gender.


Aprepitant Chemotherapy Cisplatin Emesis Risk factor 



Paul Hesketh is a consultant and has received research funding from Merck & Co. and GlaxoSmithKline, and has received honoraria from Merck & Co.

Matti Aapro is a consultant and has received research funding and honoraria from Merck & Co.

James Street is a paid consultant to Merck & Co.

Alexandra Carides is an employee of Merck Research Labs.


  1. 1.
    Booth CM, Clemons M, Dranitsaris G, Joy A, Young S, Callaghan W, Trudeau M, Petrella T (2007) Chemotherapy-induced nausea and vomiting in breast cancer patients: a prospective observational study. J Support Oncol 5:374–380PubMedGoogle Scholar
  2. 2.
    D’Acquisto R, Tyson LB, Gralla RJ (1986) The influence of a chronic high alcohol intake on chemotherapy-induced nausea and vomiting. Proc Am Soc Clin Oncol 5:257Google Scholar
  3. 3.
    Herrstedt J, Roila F (2008) Chemotherapy-induced nausea and vomiting: ESMO clinical recommendations for prophylaxis. Ann Oncol 19(Suppl 2):ii110–ii112CrossRefPubMedGoogle Scholar
  4. 4.
    Hesketh PJ (1999) Defining the emetogenicity of cancer chemotherapy regimens: relevance to clinical practice. Oncologist 4:191–196PubMedGoogle Scholar
  5. 5.
    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 21:4112–4119CrossRefPubMedGoogle Scholar
  6. 6.
    Hesketh PJ, Plagge P, Bryson JC (1992) Single-dose ondansetron for prevention of acute cisplatin-induced emesis: analysis of efficacy and prognostic factors. In: Bianchi AL, Grelot L, Miller AD (eds) Mechanisms and control of emesis. Libbey, London, pp 25–26Google Scholar
  7. 7.
    Kris MG, Hesketh PJ, Somerfield MR, Feyer P, Clark-Snow R, Koeller JM, Morrow GR, Chinnery LW, Chesney MJ, Gralla RJ, Grunberg SM (2006) American Society of Clinical Oncology guideline for antiemetics in oncology: update 2006. J Clin Oncol 24:2932–2947CrossRefPubMedGoogle Scholar
  8. 8.
    Osoba D, Zee B, Pater J, Warr D, Latreille J, Kaizer L (1997) Determinants of postchemotherapy nausea and vomiting in patients with cancer. Quality of Life and Symptom Control Committees of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 15:116–123PubMedGoogle Scholar
  9. 9.
    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 97:3090–3098CrossRefPubMedGoogle Scholar
  10. 10.
    Pollera CF, Giannarelli D (1989) Prognostic factors influencing cisplatin-induced emesis. Definition and validation of a predictive logistic model. Cancer 64:1117–1122CrossRefPubMedGoogle Scholar
  11. 11.
    Roila F, Hesketh PJ, Herrstedt J (2006) Prevention of chemotherapy- and radiotherapy-induced emesis: results of the 2004 Perugia International Antiemetic Consensus Conference. Ann Oncol 17:20–28CrossRefPubMedGoogle Scholar
  12. 12.
    Roila F, Tonato M, Basurto C, Picciafuoco M, Bracarda S, Donati D, Malacarne P, Monici L, Di Costanzo F, Patoia L et al (1989) Protection from nausea and vomiting in cisplatin-treated patients: high-dose metoclopramide combined with methylprednisolone versus metoclopramide combined with dexamethasone and diphenhydramine: a study of the Italian oncology group for clinical research. J Clin Oncol 7:1693–1700PubMedGoogle Scholar
  13. 13.
    Schwartzberg LS (2007) Chemotherapy-induced nausea and vomiting: clinician and patient perspectives. J Support Oncol 5:5–12PubMedGoogle Scholar
  14. 14.
    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 13:219–227CrossRefPubMedGoogle Scholar
  15. 15.
    Tonato M, Roila F, Del Favero A (1991) Methodology of antiemetic trials: a review. Ann Oncol 2:107–114PubMedGoogle Scholar
  16. 16.
    Warr DG, Grunberg SM, Gralla RJ, Hesketh PJ, Roila F, Wit R, Carides AD, Taylor A, Evans JK, Horgan KJ (2005) The oral NK(1) antagonist aprepitant for the prevention of acute and delayed chemotherapy-induced nausea and vomiting: pooled data from 2 randomised, double-blind, placebo controlled trials. Eur J Cancer 41:1278–1285CrossRefPubMedGoogle Scholar
  17. 17.
    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 23:2822–2830CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Paul J. Hesketh
    • 1
    Email author
  • Matti Aapro
    • 2
  • James C. Street
    • 3
  • Alexandra D. Carides
    • 4
  1. 1.Medical OncologySt. Elizabeth’s Medical CenterBostonUSA
  2. 2.Institut Multidisciplinaire d’OncologieClinique de GenolierGenolierSwitzerland
  3. 3.ReagentNew YorkUSA
  4. 4.Merck Research LaboratoiresWest PointUSA

Personalised recommendations