Phase II study of vinorelbine and low-dose docetaxel in chemotherapy-naive patients with hormone-refractory prostate cancer

Cancer J. Jul-Aug 2003;9(4):286-92. doi: 10.1097/00130404-200307000-00011.


Purpose: Vinorelbine, a semisynthetic vinca alkaloid, and docetaxel, a semisynthetic taxane, are active single agents in hormone-refractory prostate cancer and have demonstrated synergy in tumor cell lines and animal models. This study was designed to assess the efficacy and tolerability of vinorelbine and low-dose docetaxel in chemotherapy-naive, hormone-refractory prostate cancer patients whose disease had progressed after withdrawal from anti-androgens, despite castrate testosterone levels.

Patients and methods: Patients with histologically confirmed hormone-refractory prostate cancer despite testosterone levels < or = 50 ng/mL, Karnofsky performance status > 70, and adequate bone marrow reserve were enrolled. They received vinorelbine, 20 mg/m2, followed by docetaxel, 25 mg/m2, on days 1 and 8 of a 21-day cycle. Tumor response was defined by prespecified reductions from baseline prostate-specific antigen levels or bidimensionally measurable disease. Adjustments in the dose of either agent were based on > or = grade 2 toxicity according to standard criteria.

Results: Twenty-one patients with a mean age of 76 years (range, 60-83 years) and a median prostate-specific antigen level of 116 ng/mL (range, 10.4-4,262 ng/mL) were enrolled and received a total of 152 courses (median, 7.5 courses) of vinorelbine and docetaxel. Of the 19 patients who were evaluable for biochemical response, prostate-specific antigen reductions from baseline of > 75%, > or = 50% to < or = 75%, and < 50% were observed in eight, three, and seven patients, respectively (median prostate-specific antigen decrease, 60% +/- 31%). Of five patients with measurable disease, three were evaluable: one patient had a complete response, and two had partial responses at the site of measurable disease. The vinorelbine/docetaxel doublet was generally well tolerated. In the first two cycles of therapy, six patients had grade 3 and eight patients had grade 4 neutropenia as their worst-grade toxicities; all cases were manageable with granulocyte colony stimulating factor support. Acute respiratory distress syndrome was observed in one patient. There were few dose reductions or interruptions.

Discussion: Vinorelbine, 20 mg/m2, and low-dose docetaxel, 25 mg/m2, given on days 1 and 8 every 21 days, is a well-tolerated regimen with biochemical and objective response rates comparable to standard therapies in patients with hormone-refractory prostate cancer. A multicenter, randomized trial is under way to compare vinorelbine plus low-dose docetaxel with estramustine plus higher-dose docetaxel (60 mg/m2).

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Docetaxel
  • Drug Administration Schedule
  • Humans
  • Male
  • Middle Aged
  • Patient Selection
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / drug therapy*
  • Taxoids / administration & dosage
  • Testosterone / blood
  • Treatment Outcome
  • Vinblastine / administration & dosage
  • Vinblastine / analogs & derivatives*
  • Vinorelbine


  • Taxoids
  • Docetaxel
  • Testosterone
  • Vinblastine
  • Prostate-Specific Antigen
  • Vinorelbine