title: 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.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Centre Léon Bérard, 28 rue Laennec, Lyon Cedex 08, 69373, France.
authors.forename: David
authors.initials: D
authors.lastname: Pérol
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Provençal
authors.forename: Anne-Claire
authors.initials: AC
authors.lastname: Hardy-Bessard
authors.forename: David
authors.initials: D
authors.lastname: Coeffic
authors.forename: Jean-Phillipe
authors.initials: JP
authors.lastname: Jacquin
authors.forename: Cécile
authors.initials: C
authors.lastname: Agostini
authors.forename: Thomas
authors.initials: T
authors.lastname: Bachelot
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Guastalla
authors.forename: Xavier
authors.initials: X
authors.lastname: Pivot
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Martin
authors.forename: Agathe
authors.initials: A
authors.lastname: Bajard
authors.forename: Isabelle
authors.initials: I
authors.lastname: Ray-Coquard
mesh_terms: D000328:Adult; D000368:Aged; D000932:Antiemetics / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008875:Middle Aged; D009019:Morphinans / Q000627:therapeutic use*; D010936:Plant Extracts / Q000627:therapeutic use*; D011788:Quality of Life; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*; D055815:Young Adult
chemical_list: D000932:Antiemetics; D000970:Antineoplastic Agents; D009019:Morphinans; D010936:Plant Extracts; C009271:sinomenine