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.