title: Weekly docetaxel plus gemcitabine or vinorelbine in refractory advanced breast cancer patients: a parallel dose-finding study. Southern Italy Cooperative Oncology Group (SICOG).
abstract: OBJECTIVE
  The objective of this study was to determine the docetaxel MTD when combined with gemcitabine or vinorelbine in advanced breast cancer patients who had received previous anthracycline-based chemotherapy for advanced disease.
  
  
  METHODS
  Advanced breast cancer patients aged between 18 and 70 with ECOG PS 0-2 who had not responded to, or had relapsed after, first-line anthracycline-based chemotherapy, were randomized to receive either gemcitabine 1000 mg/m2 or vinorelbine 25 mg/m2 in combination with escalating doses of docetaxel (starting from 30 mg/m2), all on days 1 and 8 every three weeks. Escalation was stopped if > 33% of patients treated at a given dose level showed DLT at the first cycle.
  
  
  RESULTS
  A total of 34 patients with locally advanced (8) or metastatic disease (26) were treated, for a total of 94 cycles delivered. Nineteen patients received docetaxel in combination with gemcitabine and 15 with vinorelbine. All patients had been pretreated with anthracyclines, and 24 of 34 had also received weekly dose-dense paclitaxel. A docetaxel dose of 40/m2 proved to be safe when combined on days 1 and 8 with gemcitabine, while a dose of 35 mg/m2 was tolerated in combination with vinorelbine. Overall, nine episodes of DLT, all of them neutropenia, occurred at the first cycle. Considering all 94 cycles, grades 3 or 4 neutropenia and thrombocytopenia occurred in 15 (44%), and 7 (20%) patients. Non-hematologic toxicity was mild, except for three cases of grade 2 peripheral neuropathy. All patients were assessed for response on an 'intent-to-treat' basis. Overall, five partial responses were recorded (docetaxel + gemcitabine = 3 and docetaxel + vinorelbine = 2), for a 15% (95% CI: 5%-31%) overall response rate. Only 1 of 24 (4%) patients who had received weekly dose-dense paclitaxel responded to treatment.
  
  
  CONCLUSIONS
  The weekly docetaxel administration in combination with either gemcitabine or vinorelbine is a well-tolerated treatment for heavily pretreated advanced breast cancer patients. This approach, although sometimes capable of achieving a major response, does not seem advisable in advanced breast cancer patients refractory to both anthracyclines and paclitaxel.
authors.affiliation: Division of Medical Oncology A, National Tumor Institute of Naples, Italy. gifrasci@sirio-oncology.it
authors.forename: G
authors.initials: G
authors.lastname: Frasci
authors.forename: P
authors.initials: P
authors.lastname: Comella
authors.forename: G
authors.initials: G
authors.lastname: D'Aiuto
authors.forename: R
authors.initials: R
authors.lastname: Thomas
authors.forename: I
authors.initials: I
authors.lastname: Capasso
authors.forename: M
authors.initials: M
authors.lastname: Elmo
authors.forename: G
authors.initials: G
authors.lastname: Botti
authors.forename: G R
authors.initials: GR
authors.lastname: Cortino
authors.forename: L
authors.initials: L
authors.lastname: Lapenta
authors.forename: V
authors.initials: V
authors.lastname: De Rosa
authors.forename: P
authors.initials: P
authors.lastname: Vallone
authors.forename: A
authors.initials: A
authors.lastname: Petrillo
authors.forename: G
authors.initials: G
authors.lastname: Comella
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D043823:Taxoids; D017211:Treatment Failure; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000077235:Vinorelbine; D000093542:Gemcitabine
chemical_list: D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D014747:Vinblastine; D017239:Paclitaxel; D000077235:Vinorelbine; D000093542:Gemcitabine