title: Vinorelbine, doxorubicin, and prednisone in androgen-independent prostate cancer.
abstract: BACKGROUND
  Ultimately, patients with metastatic prostate cancer progress on androgen ablation therapy. The investigation of new chemotherapeutic regimens for the treatment of androgen-independent prostate cancer (AIPC) is essential. The authors conducted a Phase II trial with vinorelbine, doxorubicin, and daily prednisone (NAP) to investigate the antitumor activity and palliative response of this regimen in patients with AIPC.
  
  
  METHODS
  Forty-six patients entered this Phase II combination chemotherapy trial. Patients were treated with both vinorelbine and doxorubicin at doses of 20 mg/m2 on Days 1, 8, and 15 every 28 days and prednisone 5 mg twice daily. Endpoints included prostate-specific antigen (PSA) response and palliation, as measured by the Functional Assessment of Cancer Therapy-Prostate (FACT-P) instrument, the Brief Pain Inventory Scale, and a narcotic analgesic log.
  
  
  RESULTS
  The median follow-up for all 46 patients was 13.4 months. Fifty-two percent of patients had impaired performance status at baseline. One responding patient remained on NAP and was progression-free at 11.5 months. Thirty-nine patients progressed, 3 patients died prior to response assessment, and 3 patients refused therapy. The median overall survival was 57 weeks (95% confidence interval [95% CI], 36-76 weeks), and the median time to disease progression was 17 weeks (range, 11-24 weeks). The PSA response among the 36 patients who completed 3 cycles of NAP was 42% (95% CI, 26-59%). There was a statistically significant improvement in quality of life measured both by the FACT-General instrument (P = .03) and the FACT-P instrument (P = .0006) over the 3 months compared with baseline measurements. Pain medicine use also improved: The median morphine equivalents among patients who were taking pain medications at the time of study enrollment showed a substantial decline after 1 cycle of treatment that was maintained. Pain (as assessed by the Brief Pain Inventory) improved compared with baseline pain at the 2nd-month assessment (worst pain, P = .08; least pain, P = .02; and average pain, P = .003). Overall, the regimen was tolerated well. The most common side effects were mild fatigue and gastrointestinal complaints (all of which were Grade 1 or 2 [according to Version 2.0 of the Expanded Common Toxicity Criteria]). Seventeen patients (37%) experienced Grade 3 or 4 neutropenia. Five patients (11%) developed a cardiac ejection fraction of <50% during treatment and had doxorubicin discontinued. No patients developed clinical congestive heart failure.
  
  
  CONCLUSIONS
  The NAP combination produced substantive palliation and a moderate response rate in men with AIPC.
authors.affiliation: Department of Urology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
authors.forename: Lester S
authors.initials: LS
authors.lastname: Borden
authors.forename: Peter E
authors.initials: PE
authors.lastname: Clark
authors.forename: James
authors.initials: J
authors.lastname: Lovato
authors.forename: M Craig
authors.initials: MC
authors.lastname: Hall
authors.forename: Diana
authors.initials: D
authors.lastname: Stindt
authors.forename: Michele
authors.initials: M
authors.lastname: Harmon
authors.forename: Randi
authors.initials: R
authors.lastname: M Mohler
authors.forename: Frank M
authors.initials: FM
authors.lastname: Torti
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D004317:Doxorubicin / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010147:Pain Measurement; D010166:Palliative Care; D011241:Prednisone / Q000008:administration & dosage*; D017430:Prostate-Specific Antigen / Q000032:analysis; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000077235:Vinorelbine
chemical_list: D014747:Vinblastine; D004317:Doxorubicin; D017430:Prostate-Specific Antigen; D000077235:Vinorelbine; D011241:Prednisone