title: Phase II study of vinorelbine and low-dose docetaxel in chemotherapy-naive patients with hormone-refractory prostate cancer.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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).
authors.affiliation: The Boca Raton Comprehensive Cancer Center, Boca Raton, Florida, USA. ajkole@aol.com
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Koletsky
authors.forename: Manuel L
authors.initials: ML
authors.lastname: Guerra
authors.forename: Lori
authors.initials: L
authors.lastname: Kronish
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000077143:Docetaxel; D004334:Drug Administration Schedule; D006801:Humans; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy*; D043823:Taxoids / Q000008:administration & dosage; D013739:Testosterone / Q000097:blood; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000077235:Vinorelbine
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D013739:Testosterone; D014747:Vinblastine; D017430:Prostate-Specific Antigen; D000077235:Vinorelbine