title: Vinorelbine and cisplatin (CIVIC regimen) for the treatment of metastatic breast carcinoma after failure of anthracycline- and/or paclitaxel-containing regimens.
abstract: BACKGROUND
  A pilot study of a new chemotherapy, the CIVIC regimen, was performed in 58 patients with metastatic breast carcinoma previously treated with chemotherapy with or without hormonal therapy (n = 41). Cisplatin, 20 mg/m2/day, was given (Days 1-5) every 21 days during a 1-hour intravenous (i.v.) infusion, and vinorelbine (VNB) was delivered at a dose of 6 mg i.v. bolus followed by VNB, 6 mg/m2/day, in continuous i.v. infusion (Days 1-5) every 21 days.
  
  
  METHODS
  Fifty-eight patients were included in this trial between June 1992 and March 1994 (median age, 46.5 years; range, 28-69 years). The number of previous chemotherapy in the adjuvant or metastatic phase were: 1 in 9 patients, 2 in 33 patients, and > or = 3 in 16 patients. Forty-four and 12 patients, respectively, were previously treated in metastatic phase with regimens containing anthracyclines and paclitaxel. Overall, 210 cycles were given (median, 3 cycles; range, 1-6 cycles).
  
  
  RESULTS
  Among the 58 patients assessable for tumor response to the CIVIC regimen, 24 patients (41%) (95% confidence interval, 28-54) achieved an objective response (complete response or partial response) with 2 complete response (3%) and 22 partial response (38%). The median time to response was 11 weeks (range, 4-16 weeks). The median survival time from the initiation of the CIVIC regimen was 9.2 months (range, 0-45 months). The response rate was 43% (19 of 44 patients) in patients refractory to anthracyclines and 58% (7 of 12 patients) in patients with disease progression after treatment with anthracyclines and paclitaxel. Myelosuppression was the most frequent side effect. World Health Organization Grade 3 neutropenia occurred in 8 of 58 patients (14%) and in 41 of 210 cycles (20%), Grade 4 neutropenia occurred in 37 of 58 patients (64%) and in 63 of 210 cycles (30%), and Grade 3 and 4 thrombopenia occurred in 7 of 58 patients (12%) and in 9 of 210 cycles (4%). Grade 2 peripheral neuropathy was observed in 6 of 58 patients (10%) and in 12 of 210 cycles (6%), and Grade 3 peripheral neuropathy was observed in 3 of 58 patients (5%) and in 4 of 210 cycles (2%). The risk of Grade 2-3 neuropathy was significantly higher after the fourth chemotherapy cycle (14 of 23 patients vs. 3 of 35 patients: P = 0.00002).
  
  
  CONCLUSIONS
  The CIVIC regimen is effective and has acceptable tolerance in patients with metastatic breast carcinoma refractory to previous anthracycline- and/or paclitaxel-containing chemotherapy. Four cycles were found to provide the best toxicity-efficacy ratio.
authors.affiliation: Centre Léon Bérard, Lyon, France. ray@lyon.fnclcc.fr
authors.forename: I
authors.initials: I
authors.lastname: Ray-Coquard
authors.forename: P
authors.initials: P
authors.lastname: Biron
authors.forename: T
authors.initials: T
authors.lastname: Bachelot
authors.forename: J P
authors.initials: JP
authors.lastname: Guastalla
authors.forename: G
authors.initials: G
authors.lastname: Catimel
authors.forename: Y
authors.initials: Y
authors.lastname: Merrouche
authors.forename: J P
authors.initials: JP
authors.lastname: Droz
authors.forename: F
authors.initials: F
authors.lastname: Chauvin
authors.forename: J Y
authors.initials: JY
authors.lastname: Blay
mesh_terms: D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001853:Bone Marrow / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy*; D002277:Carcinoma / Q000188:drug therapy / Q000556:secondary*; D002945:Cisplatin / Q000008:administration & dosage*; D016001:Confidence Intervals; D018450:Disease Progression; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D017239:Paclitaxel / Q000008:administration & dosage / Q000627:therapeutic use*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D010865:Pilot Projects; D012074:Remission Induction; D012307:Risk Factors; D015996:Survival Rate; D013921:Thrombocytopenia / Q000139:chemically induced; D017211:Treatment Failure; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000077235:Vinorelbine
chemical_list: D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D000972:Antineoplastic Agents, Phytogenic; D014747:Vinblastine; D017239:Paclitaxel; D002945:Cisplatin; D000077235:Vinorelbine