title: Weekly administration of gemcitabine plus docetaxel in patients with advanced breast cancer: a phase 1 study.
abstract: OBJECTIVE
  This study was designed to determine the maximum tolerable dose (MTD) of gemcitabine plus docetaxel, both given on a weekly schedule, in patients with pretreated metastatic breast cancer (MBC).
  
  
  METHODS
  Heavily pretreated patients with MBC, aged 18-75 years with World Health Organization performance status of 0-2 were enrolled. Three escalating weekly doses of docetaxel (30, 35 and 40 mg/m(2)) followed by a weekly fixed dose of gemcitabine, 800 mg/m(2), were administered on days 1, 8 and 15 of a 28-day cycle. Dose-limiting toxicity (DLT) included grade > 3 hematologic toxicity and grade > 2 stomatitis, asthenia, diarrhea or organ-specific toxicity (except alopecia). Dose escalation was stopped if > or = 3 of 5 patients at any dose level experienced DLT.
  
  
  RESULTS
  Eighteen patients (median age 56 years) received a mean of 4.1 (range 1-6) cycles. Asthenia, stomatitis and leukopenia were the main DLTs. One of 5 patients had DLT at dose level 1 and 2 of 5 patients at dose level 2. At dose level 3, 3 of 5 patients had DLTs. Three additional patients treated at dose level 3 confirmed that the MTD had been reached. Therefore, the recommended docetaxel dose in combination with gemcitabine 800 mg/m(2) for phase II studies was established at the next lower dose, 35 mg/m(2). Of 12 evaluable patients, 7 (58%) achieved an objective response.
  
  
  CONCLUSIONS
  Gemcitabine 800 mg/m(2) plus docetaxel 35 mg/m(2) on days 1, 8 and 15 of a 28-day cycle is a safe regimen which shows activity in heavily pretreated patients with MBC. Further phase II investigations with this combination are now warranted.
authors.affiliation: Internal Medicine and Medical Oncology, University and IRCCS S. Matteo, Pavia, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Brugnatelli
authors.forename: Marco
authors.initials: M
authors.lastname: Danova
authors.forename: Manuela Tamburo
authors.initials: MT
authors.lastname: De Bella
authors.forename: Marina
authors.initials: M
authors.lastname: Vaglica
authors.forename: Giovanna
authors.initials: G
authors.lastname: Manuguerra
authors.forename: Alberto
authors.initials: A
authors.lastname: Riccardi
authors.forename: Sergio
authors.initials: S
authors.lastname: Palmeri
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D043823:Taxoids; D016896:Treatment Outcome; D014944:World Health Organization; D000093542:Gemcitabine
chemical_list: D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D017239:Paclitaxel; D000093542:Gemcitabine