Doxorubicin and dose-escalated cyclophosphamide with granulocyte colony-stimulating factor for the treatment of hormone-resistant prostate cancer

J Clin Oncol. 1996 May;14(5):1617-25. doi: 10.1200/JCO.1996.14.5.1617.

Abstract

Purpose: The goals of this study were to define the efficacy and toxicity of doxorubicin and dose-escalated cyclophosphamide (Cy) along with granulocyte colony-stimulating factor (G-CSF) in the treatment of hormone-refractory prostate cancer (HRPC), to determine the maximal-tolerated dose (MTD) of Cy in this regimen, and to evaluate the impact of prior pelvic irradiation (XRT) on MTD and toxicity.

Patients and methods: Thirty-five patients were treated every 21 days with fixed-dose doxorubicin (40 mg/m2) and Cy 800 to 2,000 mg/m2 (in a cohort dose-escalation schema) along with G-CSF.

Results: Five of 15 patients (33%) with measurable disease obtained an objective response. Sixteen of 35 patients (46%) had a greater than 50% decrease in prostate-specific antigen (PSA) level (95% confidence interval [CI], 28.8% to 63.4%). Ten of 35 patients (28.6%) had a greater than 75% decrease in PSA level. The median survival time was 11 months. The median survival duration of patients with a greater than 50% decrease in PSA level was 23 months, versus a median survival time of 7 months in patients without a PSA response (P = .02). Although 33% of cycles were associated with grade 4 neutropenia, febrile neutropenia occurred in only 7.8% of all cycles. Thrombocytopenia and anemia were rare. Nonhematologic toxicity was minimal. Patients who had received prior pelvic XRT had a lower Cy MTD, but their hematologic toxicity was not appreciably different.

Conclusion: This is a well-tolerated, active regimen for the treatment of HRPC. Toxicity was not different in patients with prior pelvic XRT, although these patients had a lower MTD.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / mortality
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cohort Studies
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects
  • Dose-Response Relationship, Drug
  • Doxorubicin / administration & dosage
  • Doxorubicin / adverse effects
  • Granulocyte Colony-Stimulating Factor / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / mortality
  • Survival Analysis

Substances

  • Granulocyte Colony-Stimulating Factor
  • Doxorubicin
  • Cyclophosphamide
  • Prostate-Specific Antigen