Breast Cancer Research and Treatment

, Volume 113, Issue 3, pp 529–535

A randomized study of aprepitant, ondansetron and dexamethasone for chemotherapy-induced nausea and vomiting in Chinese breast cancer patients receiving moderately emetogenic chemotherapy

  • Winnie Yeo
  • F. K. F. Mo
  • J. J. S. Suen
  • W. M. Ho
  • S. L. Chan
  • W. Lau
  • J. Koh
  • W. K. Yeung
  • W. H. Kwan
  • K. K. C. Lee
  • T. S. K. Mok
  • A. N. Y. Poon
  • K. C. Lam
  • E. K. Hui
  • B. Zee
Clinical Trial

Abstract

Objectives This is a single center, randomized, double-blind placebo-controlled study to evaluate the NK(1)-receptor antagonist, aprepitant, in Chinese breast cancer patients. The primary objective was to compare the efficacy of aprepitant-based antiemetic regimen and standard antiemetic regimen for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients who received moderately emetogenic chemotherapy. The secondary objective was to compare the patient-reported quality of life in these two groups of patients. Patients and Methods Eligible breast cancer patients were chemotherapy-naive and treated with adjuvant AC chemotherapy (i.e. doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2). Patients were randomly assigned to either an aprepitant-based regimen (day 1, aprepitant 125 mg, ondansetron 8 mg, and dexamethasone 12 mg before chemotherapy and ondansetron 8 mg 8 h later; days 2 through 3, aprepitant 80 qd) or a control arm which consisted of standard regimen (day 1, ondansetron 8 mg and dexamethasone 20 mg before chemotherapy and ondansetron 8 mg 8 h later; days 2 through 3, ondansetron 8 mg bid). Data on nausea, vomiting, and use of rescue medication were collected with a self-report diary, patients quality of life were assessed by self-administered Functional Living Index-Emesis (FLIE). Results Of 127 patients randomized, 124 were assessable. For CINV in Cycle 1 AC, there was no significant difference in the proportion of patients with reported complete response, complete protection, total control, ‘no vomiting’, ‘no significant nausea’ and ‘no nausea’. The requirement of rescue medication appears to be lesser in patients treated with the aprepitant-based regimen compared to those with the standard regimen (11% vs. 20%; P = 0.06). Assessment of FLIE revealed that while there was no difference in the nausea domain and the total score between the two groups; however, patients receiving standard antiemetic regimen had significantly worse quality of life in the vomiting domain (mean score [SD] = 23.99 [30.79]) when compared with those who received the aprepitant-based regimen (mean score [SD] = 3.40 [13.18]) (P = 0.0002). Both treatments were generally well tolerated. Patients treated with the aprepitant-based regimen had a significantly lower incidence of neutropenia (53.2% vs. 35.5%, P = 0.0468), grade ≥ 3 neutropenia (21.0% vs. 45.2, P = 0.0042) and delay in subsequent cycle of chemotherapy (8.1% vs. 27.4%, P = 0.0048). Conclusion The aprepitant regimen appears to reduce the requirement of rescue medication when compared with the control regimen for prevention of CINV in patients receiving both an anthracycline and cyclophosphamide, and is associated with a better quality of life during adjuvant AC chemotherapy.

Keywords

Chinese Antiemetic Aprepitant Chemotherapy 

References

  1. 1.
    Coates A, Abraham S, Kaye SB et al (1983) On the receiving end: patient perception of the side-effects of cancer chemotherapy. Eur J Cancer Clin Oncol 19:203–208PubMedCrossRefGoogle Scholar
  2. 2.
    Griffin AM, Butow PN, Coates AS, Childs AM, Ellis PM, Dunn SM, Tattersall MH (1996) On the receiving end. V: patient perceptions of the side effects of cancer chemotherapy in 1993. Ann Oncol 7(2):189–195PubMedGoogle Scholar
  3. 3.
    de Boer-Dennert M, de Wit R, Schmitz PI, Djontono J, v Beurden V, Stoter G, Verweij J (1997) Patient perceptions of the side-effects of chemotherapy: the influence of 5HT3 antagonists. Br J Cancer 76(8):1055–1061PubMedGoogle Scholar
  4. 4.
    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(6):1000–1006PubMedCrossRefGoogle Scholar
  5. 5.
    de Wit R, Herrstedt J, Rapoport B, Carides AD, Carides G, Elmer M, Schmidt C, Evans JK, Horgan KJ (2003) Addition of the oral NK1 antagonist aprepitant to standard antiemetics providesprotection against nausea and vomiting during multiple cycles of cisplatin-based chemotherapy. J Clin Oncol 21:4105–4111PubMedCrossRefGoogle Scholar
  6. 6.
    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 theprevention of chemotherapy-induced nausea and vomiting inpatients with breast cancer after moderately emetogenic chemotherapy. J Clin Oncol 23(12):2822–2830PubMedCrossRefGoogle Scholar
  7. 7.
    Martin AR, Pearson JD, Cai B, Elmer M, Horgan K, Lindley C (2003) Assessing the impact of chemotherapy-induced nausea and vomiting on patients’ daily lives: a modified version of the Functional Living Index-Emesis (FLIE) with 5-day recall. Support Care Cancer 11(8):522–527PubMedCrossRefGoogle Scholar
  8. 8.
    Grunberg SM, Deuson RR, Mavros P, Geling O, Hansen M, Cruciani G, Daniele B, De Pouvourville G, Rubenstein EB, Daugaard G (2004) Incidence of chemotherapy-induced nausea and emesis after modern antiemetics. Cancer 100(10):2261–2268PubMedCrossRefGoogle Scholar
  9. 9.
    Gralla RJ, Osoba D, Kris MG, Kirkbride P, Hesketh PJ, Chinnery LW, Clark-Snow R, Gill DP, Groshen S, Grunberg S, Koeller JM, Morrow GR, Perez EA, Silber JH, Pfister DG (1999) Recommendations for the use of antiemetics: evidence-based, clinical practice guidelines. J Clin Oncol 17(9):2971–2994PubMedGoogle Scholar
  10. 10.
    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. J Clin Oncol 24(18):2932–2947PubMedCrossRefGoogle Scholar
  11. 11.
    Ihbe-Heffinger A, Ehlken B, Bernard R, Berger K, Peschel C, Eichler HG, Deuson R, Thodtmann J, Lordick F (2004) The impact of delayed chemotherapy-induced nausea and vomiting on patients, health resource utilization and costs in German cancer centers. Ann Oncol 15(3):526–536PubMedCrossRefGoogle Scholar
  12. 12.
    Annemans L, Strens D, Lox E, Petit C, Malonne H (2007) Cost-effectiveness analysis of aprepitant in the prevention of chemotherapy-induced nausea and vomiting in Belgium. Support Care Cancer Oct 27 [Epub ahead of print]Google Scholar
  13. 13.
    Sanchez RI, Wang RW, Newton DJ, Bakhtiar R, Lu P, Chiu SH, Evans DC, Huskey SE (2004) Cytochrome P450 3A4 is the major enzyme involved in the metabolism of the substance P receptor antagonist aprepitant. Drug Metab Dispos 32(11):1287–1292PubMedCrossRefGoogle Scholar
  14. 14.
    Solus JF, Arietta BJ, Harris JR, Sexton DP, Steward JQ, McMunn C, Ihrie P, Mehall JM, Edwards TL, Dawson EP (2004) Genetic variation in eleven phase I drug metabolism genes in an ethnically diverse population. Pharmacogenomics 5(7):895–931PubMedCrossRefGoogle Scholar
  15. 15.
    Lamba JK, Lin YS, Schuetz EG, Thummel KE (2002) Genetic contribution to variable human CYP3A-mediated metabolism. Adv Drug Deliv Rev 54(10):1271–1294PubMedCrossRefGoogle Scholar
  16. 16.
    Hesketh PJ, Grunberg SM, Gralla RJ et al (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 21:4112–4119PubMedCrossRefGoogle Scholar
  17. 17.
    Poli-Bigelli S, Rodrigues-Pereira J, Carides AD et al (2003) Addition of the neurokinin 1 receptor antagonist aprepitant to standard antiemetic therapy improves control of chemotherapyinduced nausea and vomiting: results from a randomized, double-blind, placebo-controlled trial in Latin America. Cancer 97:3090–3098PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • Winnie Yeo
    • 1
  • F. K. F. Mo
    • 1
  • J. J. S. Suen
    • 1
  • W. M. Ho
    • 1
  • S. L. Chan
    • 1
  • W. Lau
    • 1
  • J. Koh
    • 1
  • W. K. Yeung
    • 1
  • W. H. Kwan
    • 1
  • K. K. C. Lee
    • 2
  • T. S. K. Mok
    • 1
  • A. N. Y. Poon
    • 1
  • K. C. Lam
    • 1
  • E. K. Hui
    • 1
  • B. Zee
    • 1
  1. 1.Department of Clinical Oncology, Prince of Wales Hospital Chinese University of Hong KongShatinHong Kong
  2. 2.Department of Pharmacy, Prince of Wales HospitalChinese University of Hong KongShatinHong Kong

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