Docetaxel-based chemotherapy as second-line treatment for paclitaxel-based chemotherapy-resistant hormone-refractory...

To examine docetaxel (DTX)-based chemotherapy in paclitaxel (PTX)-based chemotherapy-resistant hormone-refractory prostate cancer (HRPC) to investigate the activity and degree of toxicity in a pilot study. We have previously reported on the effectiveness of combination chemotherapy with PTX, estramustine (EMP), and carboplatin against HRPC. Although many patients with HRPC initially responded to this PTX/EMP-based combination chemotherapy, most finally progressed to PTX-resistant status within a mean of less than 1 year. DTX is an inhibitor of microtubule depolymerization like PTX and has demonstrated activity against PTX-resistant metastatic tumors.

The subjects were 15 patients with HRPC who displayed disease progression while receiving PTX/EMP/carboplatin combination chemotherapy. The patients were treated with intravenous DTX 30 mg/m2 weekly, oral EMP 10 mg/kg daily, and intravenous carboplatin (dosed to an area under the curve of 6) on day 1 of every 4-week cycle. Treatment was continued until disease progression or excessive toxicity.

Each patient received a median of eight consecutive cycles. The prostate-specific antigen level decreased by 50% or more in 33.3% of patients and by 90% or more in 13.3%. The median follow-up was 49.6 weeks, with median time to progression of 25.0 weeks and median overall survival of 54.0 weeks. One patient died of interstitial pneumonitis. One patient developed secondary osteomyelodysplastic syndrome. The major severe toxicities were grade 3 or 4 anemia in 66.7% of patients, leukopenia in 26.7%, and thrombocytopenia in 40.0%.

The results of our study have shown that DTX is comparatively active for heavily pretreated patients with PTX-resistant HRPC. However, given the significant toxicities and small subject population, well-designed Phase I-II trials of the improved regimen are warranted.