Second-line chemotherapy with docetaxel for prostate-specific antigen (PSA) relapse in men with hormone-refractory prostate cancer (HRPC) previously treated with docetaxel-based chemotherapy

Abstract

4682 Background: Docetaxel-based chemotherapy has demonstrated a significant survival benefit in men with HRPC. However, about 80% of patients demonstrate PSA relapse within 12 months and median time to progression is approximately 6 months after an initial response to docetaxel. Thus, we evaluated repeat treatment with low-dose docetaxel for men with HRPC and PSA progression. The primary endpoint was PSA response (PSA decrease ≥50%). Methods: Twenty-five consecutive patients with PSA progression after docetaxel-based chemotherapy were enrolled. PSA progression was defined as a continuous increase in PSA measured at 3 consecutive points 2 weeks apart and a PSA level ≥2x nadir after the first 12-week cycle or the previous chemotherapy cycle. PSA doubling time was ≤6 months in all patients. Docetaxel 35 mg/m2 was given on Days 2, 9, and 16 of a 4-week cycle x 3 cycles. Treatment was stopped in patients with stable disease or a PSA response (≥50% decrease in PSA from baseline, confirmed after 4 weeks). Patients were monitored with serial PSA measurements at 4-week intervals and the same 12-week sequence was restarted in patients with PSA progression. Patients who progressed during therapy were withdrawn and received palliative care. Results: Median baseline PSA level was 34.3 (range: 15–189) ng/mL. A PSA response was achieved by 18/25 (72%) patients; mean duration of response was 5.8 (range: 3–10) months. To date, 5 patients have undergone a second 12-week sequence of docetaxel owing to PSA progression; 3/5 (60%) subsequently achieved a PSA response (median follow-up: 8.5 (range: 3–15) months. Hematologic toxicity was acceptable: 5 patients (20%) and 3 patients (12%) had NCI-CTC grade 3–4 anemia and leukopenia, respectively. Grade 3–4 nonhematologic toxicities were nail changes (5 patients; 20%), diarrhea (3 patients; 12%), and fluid retention (3 patients; 12%). Conclusions: These results suggest that rechallenge with low-dose intermittent docetaxel may be an effective and well-tolerated treatment option in men with HRPC and PSA progression following an intial response to docetaxel-based chemotherapy. No significant financial relationships to disclose.