title: Phase II and pharmacologic study of docetaxel as initial chemotherapy for metastatic breast cancer.
abstract: OBJECTIVE
  Because docetaxel (Taxotere, RP 56976; Rhone-Poulenc Rorer, Antony, France) appeared to be active against breast cancer in phase I trials, we performed this phase II study.
  
  
  METHODS
  Thirty-seven patients with measurable disease were enrolled. Only prior hormone therapy was allowed, as was adjuvant chemotherapy completed > or = 12 months earlier. Docetaxel 100 mg/m2 was administered over 1 hour every 21 days. Diphenhydramine hydrochloride and/or corticosteroid premedication was added after hypersensitivity-like reactions (HSRs) were seen in two of the first six patients. Pharmacokinetic studies were performed during cycle 1 for correlation with toxicity.
  
  
  RESULTS
  Thirty-seven patients were assessable. Nineteen (51%) required dose reductions, usually for neutropenic fever. The median nadir WBC count was 1.4 x 10(3)/microL. HSRs were noted in 20 patients (54%). At a median cumulative dose of 297 mg/m2 (range, 99.6 to 424.5 mg/m2), 30 patients (81%) developed fluid retention, for which 11 (30%) subsequently stopped treatment. The first-cycle plasma area under the concentration-time curve (AUC) did not correlate with toxicity, although an ineligible patient with hepatic metastases (pretreatment bilirubin level 1.8 mg/dL) had an elevated AUC and died of toxicity. Responses were seen at all sites. On an intent-to-treat basis, there were two (5%) complete responses (CRs) and 18 (49%) partial responses (PRs). The overall response proportion (CRs plus PRs) was 54% (95% confidence interval, 37% to 71%). The median time to response was 12 weeks (range, 3 to 15) and the median duration was 26 weeks (range, 10 to 58+).
  
  
  CONCLUSIONS
  Docetaxel is active for metastatic breast cancer. Neutropenia and fluid retention are dose-limiting. The AUC did not predict toxicity, but caution is warranted when treating patients with liver dysfunction. An understanding of the pathophysiology of the fluid retention may facilitate prevention. Frequent HSR may warrant prophylactic premedication.
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Hudis
authors.forename: A D
authors.initials: AD
authors.lastname: Seidman
authors.forename: J P
authors.initials: JP
authors.lastname: Crown
authors.forename: C
authors.initials: C
authors.lastname: Balmaceda
authors.forename: R
authors.initials: R
authors.lastname: Freilich
authors.forename: T A
authors.initials: TA
authors.lastname: Gilewski
authors.forename: T B
authors.initials: TB
authors.lastname: Hakes
authors.forename: V
authors.initials: V
authors.lastname: Currie
authors.forename: D E
authors.initials: DE
authors.lastname: Lebwohl
authors.forename: J
authors.initials: J
authors.lastname: Baselga
authors.forename: G
authors.initials: G
authors.lastname: Raptis
authors.forename: M
authors.initials: M
authors.lastname: Gollub
authors.forename: M
authors.initials: M
authors.lastname: Robles
authors.forename: R
authors.initials: R
authors.lastname: Bruno
authors.forename: L
authors.initials: L
authors.lastname: Norton
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D002927:Cimetidine / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D004155:Diphenhydramine / Q000008:administration & dosage; D000077143:Docetaxel; D004334:Drug Administration Schedule; D004342:Drug Hypersensitivity / Q000209:etiology / Q000517:prevention & control; D004487:Edema / Q000139:chemically induced; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007970:Leukopenia / Q000139:chemically induced; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011292:Premedication; D043823:Taxoids
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D000077143:Docetaxel; D003907:Dexamethasone; D002927:Cimetidine; D004155:Diphenhydramine; D017239:Paclitaxel