title: Prospective multicenter randomized phase III study of weekly versus standard docetaxel (D2) for first-line treatment of metastatic breast cancer.
abstract: OBJECTIVE
  Previous phase II studies have indicated a greatly reduced hematotoxicity of docetaxel-based regimens administered on weekly schedules. The present trial was initiated to randomly compare the toxicity and efficacy of weekly docetaxel versus its standard 3-weekly application.
  
  
  METHODS
  Patients previously untreated with chemotherapy for metastatic disease were recruited. Patients aged >60 years or with a Karnofsky Perfomance Status (KPS) of 60-80% were eligible for the D2 study. Patients were randomized to receive docetaxel either on a 3-weekly [75 mg/m(2) every 3 weeks (q3w)] or on a weekly (30 mg/m(2) on days 1, 8, and 15; q4w) schedule. Treatment was continued until a maximum of 8 cycles, unacceptable toxicity, or disease progression. All patients received standard corticosteroid prophylaxis.
  
  
  RESULTS
  Since statistical significance for the primary endpoint (toxicity) was achieved in the interim analysis, the study was closed according to the study protocol (102 of 162 patients). Compared to the standard arm, leukopenia ≥grade 3 was a rare event in the weekly arm of the D2 study (per-patient analysis: 4.2% q1w vs. 51.9% q3w; p < 0.0001). No difference was observed between the 2 schedules regarding the occurrence of anemia or thrombocytopenia. With regard to nonhematological toxicity, there was a higher incidence of skin/nail and hepatological toxicity with the weekly schedule, whereas neurotoxicity was observed more often in the standard arm. The rate of omitted doses was significantly increased in the weekly arm (8.6% q1w vs. 0% q3w). The overall response rate was 22.9% in the weekly arm compared to 42.6% in the standard arm (p = 0.039). Time to progression was 5.4 (q1w) versus 6.3 (q3w) months (p = 0.91), and overall survival was 22.7 (q1w) versus 15.8 (q3w) months (p = 0.24).
  
  
  CONCLUSIONS
  The present data support the feasibility of both weekly and 3-weekly application of docetaxel. As expected, severe leukopenia seems avoidable in weekly scheduled single-agent docetaxel and may serve as an important treatment option, particularly in elderly patients and patients with a reduced performance status.
authors.affiliation: Department of Internal Medicine III, Klinikum Grosshadern, Ludwig Maximilian University of Munich, Munich, Germany. Joachim.Stemmler@med.uni-muenchen.de
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Stemmler
authors.forename: Nadia
authors.initials: N
authors.lastname: Harbeck
authors.forename: Isolde
authors.initials: I
authors.lastname: Gröll de Rivera
authors.forename: Ursula
authors.initials: U
authors.lastname: Vehling Kaiser
authors.forename: Gerhard
authors.initials: G
authors.lastname: Rauthe
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Abenhardt
authors.forename: Almut
authors.initials: A
authors.lastname: Artmann
authors.forename: Harald
authors.initials: H
authors.lastname: Sommer
authors.forename: Hans-Gerd
authors.initials: HG
authors.lastname: Meerpohl
authors.forename: Marion
authors.initials: M
authors.lastname: Kiechle
authors.forename: Volker
authors.initials: V
authors.lastname: Heinemann
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000077143:Docetaxel; 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; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000556:secondary; D015996:Survival Rate; D043823:Taxoids / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel