title: The combination of gemcitabine and vinorelbine is an active regimen as second-line therapy in patients with metastatic breast cancer pretreated with taxanes and/or anthracyclines: a phase I-II study.
abstract: OBJECTIVE
  To evaluate the activity and toxicity of gemcitabine and vinorelbine (GemVin), in patients with advanced breast cancer, previously treated with anthracyclines alone or with taxanes. Patients and methods. Nine patients were entered into the phase I and 50 patients were entered into the phase II study. Gemcitabine was administered beginning with the dose of 800 mg/m2 and vinorelbine was given at the fixed dose of 25 mg/m2, both on days 1 and 8, every 21 days. Escalated dose levels of gemcitabine were planned by increments of 200 mg/m2 per level. The median age of the 50 assessable patients for the phase II study was 56.5 years (range 30-70) and median performance status (PS, ECOG score), 1 (range 0-2). The dominant sites of metastases were viscera in 40, bone in five and soft tissue in five patients. First-line chemotherapy for metastatic disease with taxanes and anthracyclines or with anthracyclines alone was administered in 36 and 14 patients, respectively.
  
  
  RESULTS
  The optimal schedule for the combination was gemcitabine 800 mg/m2 and vinorelbine 25 mg/m2. The maximum tolerated dose of gemcitabine was 1000 mg/m2, with grade 4 neutropenia occurring in two cases at this dose level. Overall, 267 cycles were given to the 50 patients enrolled into the phase II (mean 5.3; range 3-9). The schedule was well tolerated: three patients experienced grade 4 neutropenia and another four patients experienced grade 3 anemia. Non-hematological toxicities were moderate. A major objective response was observed in 42% of patients (95% confidence interval (CI), 28-57%), with complete remission in four (8%) and partial response in 17 (34%) patients. The median time to progression was 6 months. Activity as well as toxicity were similar in the subgroups of the patients pretreated either with combinations of taxanes and anthracyclines or anthracyclines alone.
  
  
  CONCLUSIONS
  The optimal GemVin schedule is an effective and well tolerated second-line therapy in patients with metastatic breast cancer pre-treated with anthracycline-based schedules or with combinations of anthracyclines and taxanes.
authors.affiliation: Division of Oncology, Azienda Ospedaliera San Filippo Neri, Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Morabito
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Filippelli
authors.forename: Sergio
authors.initials: S
authors.lastname: Palmeri
authors.forename: Stefano
authors.initials: S
authors.lastname: Cascinu
authors.forename: Francesco
authors.initials: F
authors.lastname: Ferraù
authors.forename: Vittorina
authors.initials: V
authors.lastname: Zagonel
authors.forename: Domenico
authors.initials: D
authors.lastname: Gattuso
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Catalano
authors.forename: Barbara
authors.initials: B
authors.lastname: Capaccetti
authors.forename: Vittorio
authors.initials: V
authors.lastname: Franciosi
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Accurso
authors.forename: Fedele
authors.initials: F
authors.lastname: Scinto
authors.forename: Giampietro
authors.initials: G
authors.lastname: Gasparini
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D001952:Bridged-Ring Compounds / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D004338:Drug Combinations; D005260:Female; D006801:Humans; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009362:Neoplasm Metastasis; D043823:Taxoids; D014747:Vinblastine / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D000077235:Vinorelbine; D000093542:Gemcitabine
chemical_list: D018943:Anthracyclines; D000970:Antineoplastic Agents; D001952:Bridged-Ring Compounds; D004338:Drug Combinations; D043823:Taxoids; D003841:Deoxycytidine; C080625:taxane; D014747:Vinblastine; D000077235:Vinorelbine; D000093542:Gemcitabine