title: Bi-weekly docetaxel in the adjuvant treatment of node-positive or high-risk breast cancer patients: phase I study of the Shiga Breast Cancer Study Group.
abstract: BACKGROUND
  A phase I study of bi-weekly docetaxel was performed to determine the maximum tolerated dose (MTD) as well as the incidence and severity of toxicities in patients with high-risk node-negative and node-positive breast cancer.
  
  
  METHODS
  Docetaxel was administered every 14 days to postoperative breast cancer patients who were axillary lymph node-positive or considered at high-risk. After the completion of six cycles of docetaxel, all patients received epirubicin + cyclophosphamide every 21 days for four cycles. The docetaxel dose was escalated in a stepwise fashion as follows: 45, 50, 55, 60, 65, and 70 mg/m(2) in levels 1, 2, 3, 4, 5, and 6, respectively. Patients were treated in cohorts of three to six per group using a standard phase I study design. The MTD was considered the dose level at which three of three patients or more than three of six patients experienced dose-limiting toxicity (DLT) in the first cycle.
  
  
  RESULTS
  Twenty patients were enrolled and received a total of 110 cycles of chemotherapy. The MTD was not reached until level 5. Since three DLTs (grade 3 diarrhea, n = 2; grade 3 constipation, n = 1), were observed in five patients at level 6, level 6 was judged as the MTD. The recommended dose of bi-weekly docetaxel for a phase II trial is 65 mg/m(2).
  
  
  CONCLUSIONS
  The MTD of bi-weekly docetaxel was 70 mg/m(2). Further evaluation is warranted to confirm the safety and efficacy in the treatment of early-stage breast cancer.
authors.affiliation: Division of General Surgery, Department of Surgery, Shiga University of Medical Science, Seta-Tsukinowa, Otsu, Shiga, 520-2192, Japan. abe@belle.shiga-med.ac.jp
authors.forename: Hajime
authors.initials: H
authors.lastname: Abe
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ogawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Okino
authors.forename: Makoto
authors.initials: M
authors.lastname: Kato
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Sako
authors.forename: Haruo
authors.initials: H
authors.lastname: Sano
authors.forename: Takumi
authors.initials: T
authors.lastname: Shimomatsuya
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Suwa
authors.forename: Shunichi
authors.initials: S
authors.lastname: Higashide
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D000077143:Docetaxel; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007564:Japan; D008207:Lymphatic Metastasis; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D043823:Taxoids / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel