ABSTRACT
Although the majority of men with metastatic prostate cancer respond initially to and rogen ablation, most of them will eventually develop hormone-refractory progressive disease; with generally median survival less than one year from that point. The management of hormone refractory prostate cancer [HRPC] is challenging, as there is no uniformly accepted strategy. Combinations of estramustine and taxanes produced objective responses in soft tissue, reductions in serum PSA levels, and relief from bone pains. Different dosing and frequency of palliative chemo-hormonal therapy [docetaxel-estramustine] was evaluated in HRPC in relation to overall response, toxicity and survival. 21 patients with progressive, metastatic HRPC were r and omized to receive either [I] estramustine 280 mg PO tid, [Dl-5] with docetaxel as 70 mg/m[2] [1 hour infusion- D2] and recycling 3 weeks or [II] docetaxel 35 mg/m[2] [1 hour infusion] weekly for 3 consecutive weeks and estramustine 140 mg PO tid on days [Dl-3], [D8-10] and [D15-17] with recycling every 4 weeks. Primary endpoint was time to progression. However secondary endpoints were response rate, toxicity and survival. Twenty one patients were presented with a median age of 69 years [range, 49-78 years], median Gleason score of 8 [range, 6-10]. Metastases to bones and lymph nodes were present in 85.7% and 38.1% of total cases respectively. PSA response was statistically higher in weekly regimen than conventional schedule [75% vs. 44.4%], while partial response and pain relief was [22.2% vs. 33.3%] in conventional schedule compared to [44.4% vs. 50%] in weekly regimen respectively [p>0.05]. Median time to progression was [6.1 months vs. 5.6 months]; median survival [18.2 months vs. 16.5 months] and overall 1 year survival [77.8% vs. 66.7%] in conventional schedule vs. weekly regimen respectively. Grade III/IV of neutropenia occurred in 44.4% vs. 25% in conventional schedule treatment and weekly regimen respectively [p<0.05]. Neutropenic fever occurred only in one patient [11.1%] in conventional schedule group. Docetaxel-estramustine is a good effective combination of chemo-hormonal treatment used for hormonerefractory prostate cancer. Even though administration of lower weekly doses of doctaxel-estramustine does not seem to have statistically significant effect on time to disease progression and survival, but criteria of objective response rate with increase PSA response and measurable disease response and subjective improvement of pain are promising. Hematological toxicity, fatigue, fluid retention, attacks of thrombosis and neurotoxicities were lower in weekly regimen compared to conventional schedule. Nevertheless, the data presented here suggest that additional larger r and omized studies of [docetaxel plus estramustine] in lower doses and intermittent schedule are needed to better evaluate the efficacy and survival outcome of this regimen in men with HRPC