Phase II and pharmacologic study of docetaxel as initial chemotherapy for metastatic breast cancer Journal Article


Authors: Hudis, C. A.; Seidman, A. D.; Crown, J. P. A.; Balmaceda, C.; Freilich, R.; Gilewski, T. A.; Hakes, T. B.; Currie, V.; Lebwohl, D. E.; Baselga, J.; Raptis, G.; Gollub, M.; Robles, M.; Bruno, R.; Norton, L.
Article Title: Phase II and pharmacologic study of docetaxel as initial chemotherapy for metastatic breast cancer
Abstract: Purpose: 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. Patients and Methods: Thirty-seven patients with measurable disease were enrolled. Only prior hormone therapy was allowed, as was adjuvant chemotherapy completed ≥ 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 × 103/ μL. 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+). Conclusion: 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. © 1996 by American Society of Clinical Oncology.
Keywords: adult; clinical article; controlled study; aged; middle aged; clinical trial; neutropenia; dose response; hypertension; side effect; liver dysfunction; paclitaxel; neurotoxicity; edema; metastasis; controlled clinical trial; phase 2 clinical trial; leukopenia; nausea; randomized controlled trial; drug administration schedule; antineoplastic agents, phytogenic; dexamethasone; clinical protocol; breast neoplasms; docetaxel; abdominal pain; drug hypersensitivity; dyspnea; fever; pruritus; drug mechanism; breast carcinoma; neoplasm metastasis; drug clearance; taxoids; hypersensitivity reaction; intravenous drug administration; injections, intravenous; bronchospasm; fluid retention; angioneurotic edema; diphenhydramine; premedication; cimetidine; humans; human; female; priority journal; article
Journal Title: Journal of Clinical Oncology
Volume: 14
Issue: 1
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 1996-01-01
Start Page: 58
End Page: 65
Language: English
PUBMED: 8558221
PROVIDER: scopus
DOI: 10.1200/jco.1996.14.1.58
DOI/URL:
Notes: Article -- Export Date: 22 November 2017 -- Source: Scopus
Altmetric Score
MSK Authors
  1. Andrew D Seidman
    244 Seidman
  2. Clifford Hudis
    840 Hudis
  3. Larry Norton
    562 Norton
  4. Marc J Gollub
    105 Gollub
  5. Violante Currie
    30 Currie
  6. Jose T Baselga
    395 Baselga
  7. George   Raptis
    21 Raptis