Docetaxel re-treatment for metastatic hormone refractory prostate cancer

Abstract

16066 Background: Recent clinical trials have established three-weekly docetaxel chemotherapy along with prednisolone (3wD+P) as standard of care for patients with metastatic hormone refractory prostate cancer (MHRPC). A significant proportion of patients receiving first- line 3wD chemotherapy (CT) will be eligible for second-line CT on biochemical disease progression (BDP), however, there are no other licensed CT options. The efficacy and toxicity with 3wD CT re-treatment has not been previously reported in patients who respond to docetaxel and then progress after a period of biochemical remission. Methods: A total of43 patients with MHRPC were treated at our institution with 3wD 75 mg/m2 + P 10 mg daily. The median patient age was 73 years and the median PSA at CT initiation was 182 (range 19.9->1500) ng/ml. Of 43 patients, 10 were re-treated with 3wD+P (2nd line CT) on BDP. A further 3 out of these 10 patients received 2nd re-treatment with 3wD+P (3rd line CT) on BDP. We assessed PSA response, toxicity, overall survival for first-line docetaxel CT and subsequent re-treatment. Results: Of 43 patients, 37% had PSA decline of >50% and 14% had PSA declines of 30–50% of pre-treatment levels; 19% had stable disease and 23% had progressive disease. On 1st re-treatment, 7 out of 10 patients who had responded to first-line CT responded again with a PSA reduction >50%. 3 out of these 7 patients received 2nd re-treatment, with all 3 patients achieving PSA reduction >50% of pre-treatment levels. The median treatment-free interval prior to 1st and 2nd re-treatments was 24 and 26 weeks, respectively. The median overall survival was 16 (range 1–35) months. There was a significant rise in the incidence of grade 3/4 neutropenia with re-treatment, though no treatment-related deaths. Conclusions: To our knowledge, this is the first evidence supporting 3wD re-treatment, demonstrating that MHRPC patients responding to 1st line docetaxel CT maintain their intrinsic sensitivity to subsequent re-treatment. Analogous to intermittent androgen ablation, intermittent administration of CT is an attractive proposition which may offer patients improved quality of life during treatment-free periods. Based on these results, the role of intermittent 3wD CT needs to be prospectively evaluated in clinical trials. No significant financial relationships to disclose.