title: Phase II study of sequential administration of docetaxel followed by doxorubicin and cyclophosphamide as first-line chemotherapy in metastatic breast cancer.
abstract: OBJECTIVE
  To evaluate the feasibility and efficacy of a sequential administration of four cycles of docetaxel (100 mg/m(2) every 3 weeks) followed by four cycles of doxorubicin and cyclophosphamide (AC; 60/600 mg/m(2) every 3 weeks), with subsequent consolidation with docetaxel or AC, as first-line chemotherapy in patients with metastatic breast cancer (MBC).
  
  
  METHODS
  Forty-eight patients received 443 cycles of chemotherapy (median, 11 cycles/patient; range, 1 to 13 cycles). A total of 267 cycles of docetaxel (60.3%) and 176 of AC (39.7%) were given. Consolidation therapy was given to 33 patients (29 with docetaxel).
  
  
  RESULTS
  Grade 4 neutropenia was the most frequent toxicity (83% of patients). This was not cumulative and was rarely complicated by febrile neutropenia or severe infection. The nonhematologic safety profile was favorable: there were no grade 4 adverse events, and grade 3 episodes were infrequent. Docetaxel-specific toxicities were generally not severe. With a median cumulative doxorubicin dose of 397 mg/m(2) (range, 150 to 543 mg/m(2)), two incidences of unrelated congestive heart failure after further treatment with anthracyclines and two of asymptomatic left ventricular ejection fraction decrease were observed. Among the 42 assessable patients, five (12%) had complete and 25 (60%) had partial responses, for an overall response rate of 71% (95% confidence interval, 55% to 84%). Median duration of response was 53 weeks (range, 12 to 72 weeks), and median time to progression was 46 weeks (range, 3 of 72 weeks). With a median follow-up of 40.4 months, median survival was 32 months (range, 2 to 55 months).
  
  
  CONCLUSIONS
  This docetaxel-based sequential schedule is safe and effective in first-line therapy for MBC, without incurring cumulative toxicity, and provides a feasible chemotherapeutic option in this clinical setting.
authors.affiliation: Hôpital de la Pitié Salpétrière, Paris, France. david.khayat@psl.ap-hop-paris.fr
authors.forename: D
authors.initials: D
authors.lastname: Khayat
authors.forename: P
authors.initials: P
authors.lastname: Chollet
authors.forename: E C
authors.initials: EC
authors.lastname: Antoine
authors.forename: S
authors.initials: S
authors.lastname: Monfardini
authors.forename: G
authors.initials: G
authors.lastname: Ambrosini
authors.forename: A
authors.initials: A
authors.lastname: Benhammouda
authors.forename: M F
authors.initials: MF
authors.lastname: Mazen
authors.forename: R
authors.initials: R
authors.lastname: Sorio
authors.forename: O
authors.initials: O
authors.lastname: Borg-Olivier
authors.forename: A
authors.initials: A
authors.lastname: Riva
authors.forename: C
authors.initials: C
authors.lastname: Ramazeilles
authors.forename: N
authors.initials: N
authors.lastname: Azli
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000008:administration & dosage / Q000031:analogs & derivatives; D012074:Remission Induction; D016019:Survival Analysis; D043823:Taxoids
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D004317:Doxorubicin; D003520:Cyclophosphamide; D017239:Paclitaxel