title: Vinorelbine combined with paclitaxel infused over 96 hours (VI-TA-96) for patients with metastatic breast carcinoma.
abstract: BACKGROUND
  Vinorelbine (VI) and paclitaxel (TA) are among the most active single agents in the treatment of patients with breast carcinoma, and both have microtubules as their cytotoxic target. This Phase I-II study combined these 2 agents and used a 96-hour intravenous (i.v.) infusion of paclitaxel to maximize their cytotoxic activities.
  
  
  METHODS
  Patients with metastatic breast carcinoma who were previously treated with chemotherapy were administered increasing doses of a 96-hour paclitaxel i.v. infusion from Days 1 to 5, with a first fixed dose of vinorelbine (12.5 mg/m(2) on Days 1 and 5) every 3 weeks. The dose of paclitaxel was then decreased starting from the previously established tolerated dose, and a second fixed dose of vinorelbine (15 mg/m(2) on Days 1 and 5) was given. This identified 2 acceptable doses of paclitaxel (110 mg/m(2) with VI 12.5 mg/m(2) and 90 mg/m(2) with VI 15 mg/m(2)). The latter was used in the subsequent Phase II study.
  
  
  RESULTS
  For the 50 patients treated with any dose, the complete response (CR) and the CR plus partial response (PR) rates were, respectively, 14% and 48% (95% confidence interval [CI], 34-67%). When only the 27 patients treated with the Phase II dose were considered, the figures were, respectively, 11% and 52% (95% CI, 42-62%). The median time to progression was 26 weeks, and the median survival 51 weeks. The dose-limiting toxicity was febrile neutropenia.
  
  
  CONCLUSIONS
  At the dose schedule identified for the Phase II study, the VI-TA-96 combination has considerable antitumor activity; pharmacoeconomic interest (it requires about half the doses of the agents administered singly); no major toxicity, except G4 neutropenia; and no need for premedication. This combination may be recommended as one of the most effective therapeutic options for patients with metastatic breast carcinoma who were pretreated mainly with anthracycline-containing chemotherapy.
authors.affiliation: Medical Oncology Division, University Hospital, Parma, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Cocconi
authors.forename: A
authors.initials: A
authors.lastname: Mambrini
authors.forename: M
authors.initials: M
authors.lastname: Quarta
authors.forename: G
authors.initials: G
authors.lastname: Vasini
authors.forename: M A
authors.initials: MA
authors.lastname: Bella
authors.forename: F
authors.initials: F
authors.lastname: Ferrozzi
authors.forename: M D
authors.initials: MD
authors.lastname: Beretta
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D017850:Economics, Pharmaceutical; D005260:Female; D005334:Fever / Q000139:chemically induced; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000077235:Vinorelbine
chemical_list: D014747:Vinblastine; D017239:Paclitaxel; D000077235:Vinorelbine