Can treatment with Cocculine improve the control of chemotherapy-induced emesis in early breast cancer patients? A randomized, multi-centered, double-blind, placebo-controlled Phase III trial
Chemotherapy induced nausea and vomiting (CINV) remains a major problem that seriously impairs the quality of life (QoL) in cancer patients receiving chemotherapy regimens. Complementary medicines, including homeopathy, are used by many patients with cancer, usually alongside with conventional treatment. A randomized, placebo-controlled Phase III study was conducted to evaluate the efficacy of a complex homeopathic medicine, Cocculine, in the control of CINV in non-metastatic breast cancer patients treated by standard chemotherapy regimens.
Chemotherapy-naïve patients with non-metastatic breast cancer scheduled to receive 6 cycles of chemotherapy including at least three initial cycles of FAC 50, FEC 100 or TAC were randomized to receive standard anti-emetic treatment plus either a complex homeopathic remedy (Cocculine, registered in France for treatment of nausea and travel sickness) or the matching placebo (NCT00409071 clinicaltrials.gov). The primary endpoint was nausea score measured after the 1st chemotherapy course using the FLIE questionnaire (Functional Living Index for Emesis) with 5-day recall. Secondary endpoints were: vomiting measured by the FLIE score, nausea and vomiting measured by patient self-evaluation (EVA) and investigator recording (NCI-CTC AE V3.0) and treatment compliance.
From September 2005 to January 2008, 431 patients were randomized: 214 to Cocculine (C) and 217 to placebo (P). Patient characteristics were well-balanced between the 2 arms. Overall, compliance to study treatments was excellent and similar between the 2 arms. A total of 205 patients (50.9%; 103 patients in the placebo and 102 in the homeopathy arms) had nausea FLIE scores > 6 indicative of no impact of nausea on quality of life during the 1st chemotherapy course. There was no difference between the 2 arms when primary endpoint analysis was performed by chemotherapy stratum; or in the subgroup of patients with susceptibility to nausea and vomiting before inclusion. In addition, nausea, vomiting and global emesis FLIE scores were not statistically different at any time between the two study arms. The frequencies of severe (Grade ≥ 2) nausea and vomiting were low in our study (nausea: P: 17.6% vs C: 15.7%, p=0.62; vomiting: P: 10.8% vs C: 12.0%, p=0.72 during the first course).
This double-blinded, placebo-controlled, randomised Phase III study showed that adding a complex homeopathic medicine (Cocculine) to standard anti-emetic prophylaxis does not improve the control of CINV in early breast cancer patients.
- Coleman MP: Trends in breast cancer incidence, survival, and mortality. Lancet 2000,356(9229):590–591. CrossRef
- Glaus A, Fah B, Hornung R, Senn H, Stiefel F: [Breast cancer prevention behaviour: a perspective of women from three language regions of Switzerland]. Pflege 2004,17(6):385–394. CrossRef
- Lohr L: Chemotherapy-induced nausea and vomiting. Cancer J 2008,14(2):85–93. CrossRef
- Gralla RJ, Kris MG, Tyson LB, Clark RA: Controlling emesis in patients receiving cancer chemotherapy. Recent Results Cancer Res 1988, 108:89–101. CrossRef
- Rusthoven JJ, Osoba D, Butts CA, Yelle L, Findlay H, Grenville A: The impact of postchemotherapy nausea and vomiting on quality of life after moderately emetogenic chemotherapy. Support Care Cancer 1998,6(4):389–395. CrossRef
- Bernhard J, Maibach R, Thurlimann B, Sessa C, Aapro MS: Patients' estimation of overall treatment burden: why not ask the obvious? J Clin Oncol 2002,20(1):65–72. CrossRef
- Grunberg SM, Rolski J, Strausz J, et al.: Efficacy and safety of casopitant mesylate, a neurokinin 1 (NK1)-receptor antagonist, in prevention of chemotherapy-induced nausea and vomiting in patients receiving cisplatin-based highly emetogenic chemotherapy: a randomised, double-blind, placebo-controlled trial. Lancet Oncol 2009,10(6):549–558. CrossRef
- Borjeson S, Hursti TJ, Tishelman C, Peterson C, Steineck G: Treatment of nausea and emesis during cancer chemotherapy. Discrepancies between antiemetic effect and well-being. J Pain Symptom Manage 2002,24(3):345–358. CrossRef
- Grunberg SM, Osoba D, Hesketh PJ, et al.: Evaluation of new antiemetic agents and definition of antineoplastic agent emetogenicity–an update. Support Care Cancer 2005,13(2):80–84. CrossRef
- Kris MG, Hesketh PJ, Herrstedt J, et al.: Consensus proposals for the prevention of acute and delayed vomiting and nausea following high-emetic-risk chemotherapy. Support Care Cancer 2005,13(2):85–96. CrossRef
- Feyer P, Jordan K: Update and new trends in antiemetic therapy: the continuing need for novel therapies. Ann Oncol 2011,22(1):30–38. CrossRef
- Roila F, Herrstedt J, Aapro M, et al.: 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 2010,21(Suppl 5):v232-v243. CrossRef
- Glaus A, Knipping C, Morant R, et al.: Chemotherapy-induced nausea and vomiting in routine practice: a European perspective. Support Care Cancer 2004,12(10):708–715. CrossRef
- Ernst E, Cohen L, Gerner J, et al.: 'Alternative cancer cures': looking for common ground. Lancet Oncol 2000,1(1):54–59. CrossRef
- Molassiotis A, Fernadez-Ortega P, Pud D, et al.: Use of complementary and alternative medicine in cancer patients: a European survey. Ann Oncol 2005,16(4):655–663. CrossRef
- Genre D, Tarpin C, Braud AC, Camerlo J, Protiere C, Eisinger F, Viens P: Randomized, double-blind study comparing homeopathy (cocculine) to placebo in prevention of nausea/vomiting among patients receiving adjuvant chemotherapy for breast cancer. Breast Cancer Research and Treatment 2003,82(sup 1):637.
- Kris MG, Hesketh PJ, Somerfield MR, et al.: American Society of Clinical Oncology guideline for antiemetics in oncology: update 2006. J Clin Oncol 2006,24(18):2932–2947. CrossRef
- Decker GM, DeMeyer ES, Kisko DL: Measuring the maintenance of daily life activities using the functional living index-emesis (FLIE) in patients receiving moderately emetogenic chemotherapy. J Support Oncol 2006,4(1):35–41. 52
- Martin AR, Pearson JD, Cai B, Elmer M, Horgan K, Lindley C: 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 2003,11(8):522–527. CrossRef
- Montgomery GH, Bovbjerg DH: Expectations of chemotherapy-related nausea: emotional and experiential predictors. Ann Behav Med 2003,25(1):48–54. CrossRef
- Roscoe JA, Bushunow P, Morrow GR, et al.: Patient expectation is a strong predictor of severe nausea after chemotherapy: a University of Rochester Community Clinical Oncology Program study of patients with breast carcinoma. Cancer 2004,101(11):2701–2708. CrossRef
- Griffin AM, Butow PN, Coates AS, et al.: On the receiving end. V: Patient perceptions of the side effects of cancer chemotherapy in 1993. Ann Oncol 1996,7(2):189–195. CrossRef
- Rostock M, Naumann J, Guethlin C, Guenther L, Bartsch HH, Walach H: Classical homeopathy in the treatment of cancer patients–a prospective observational study of two independent cohorts. BMC Cancer 2011, 11:19. CrossRef
- Kassab S, Cummings M, Berkovitz S, Van HR, Fisher P: Homeopathic medicines for adverse effects of cancer treatments. Cochrane Database Syst Rev 2009., (2): CD004845
- Thompson EA, Reillly D: The homeopathic approach to symptom control in the cancer patient: a prospective observational study. Palliat Med 2002,16(3):227–233. CrossRef
- Moschen R, Kemmler G, Schweigkofler H, et al.: Use of alternative/complementary therapy in breast cancer patients–a psychological perspective. Support Care Cancer 2001,9(4):267–274. CrossRef
- Eisenberg DM, Davis RB, Ettner SL, et al.: Trends in alternative medicine use in the United States, 1990–1997: results of a follow-up national survey. JAMA 1998,280(18):1569–1575. CrossRef
- Jonas WB, Kaptchuk TJ, Linde K: A critical overview of homeopathy. Ann Intern Med 2003,138(5):393–399.
- Frenkel M: Homeopathy in cancer care. Altern Ther Health Med 2010,16(3):12–16.
- The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/12/603/prepub
- Can treatment with Cocculine improve the control of chemotherapy-induced emesis in early breast cancer patients? A randomized, multi-centered, double-blind, placebo-controlled Phase III trial
- Open Access
- Available under Open Access This content is freely available online to anyone, anywhere at any time.
- Online Date
- December 2012
- Online ISSN
- BioMed Central
- Additional Links
- Early breast cancer
- Adjuvant chemotherapy
- Nausea and vomiting
- Quality of life
- Industry Sectors
- Author Affiliations
- 1. Centre Léon Bérard, 28 rue Laennec, Lyon Cedex 08, 69373, France
- 2. Centre hospitalier de la région d’Annecy, 1 avenue de l’hôpital, Annecy, BP90074, 74374, France
- 3. Clinique armoricaine de Radiologie, 21 rue du Vieux Séminaire, Saint Brieuc, 22 000, France
- 4. UMGEC, Service Institut Daniel Hollard, 12 Rue Docteur Calmette, Grenoble, 38028, France
- 5. Institut de cancérologie de la Loire, 108, avenue Albert-Raimond, Saint-Priest-en-Jarez, 42270, France
- 6. Centre hospitalier Général, Chambéry, BP1125, 73011, France
- 7. Centre Hospitalier Universitaire, Boulevard Fleming, Besançon, 25030, France
- 8. Hôpital Jean Mermoz, 55 avenue Jean Mermoz, Lyon, 69008, France
- 9. Centre Léon Bérard, 28 rue Laennec, Lyon, 69008, France