The use of bisphosphonate for the palliative treatment of painful bone metastasis due to hormone refractory prostate cancer

Purpose: Hormone refractory prostate cancer is dominated by osseous metastases leading to bone pain and pathological fractures. We assessed the clinical efficacy of bisphosphonate in the management of symptomatic skeletal metastases due to prostate cancer. Materials and Methods: A total of 85 patients with painful osseous metastases due to hormone refractory prostate cancer were treated with clodronate in an open prospective nonrandomized clinical study. Clodronate was started as an intravenous phase for 8 days at a dose of 300 mg. daily followed by an oral maintenance phase of 1,600 mg. daily. The primary study end point was decreased pain without an increase in analgesic medication for at least 2 consecutive measurements. Secondary end points were decreased analgesics, an improved Karnofsky index and mobility as well as the duration of bisphosphonate action. Decreased pain was documented by a 10-point visual analog scale and consumption of analgesics was documented in a diary. Results: A palliative response with a significant decrease in mean pain score from 7.9 (range 6 to 10) to 2.5 (range 0 to 4) (p <0.001) was achieved in 64 of the 85 patients (75%), 19 (22%) were completely pain-free without further need of analgesics and 45 significantly decreased the daily consumption of analgesics. The mean duration of bisphosphonate action was 9 weeks (range 4 to 22) and mean survival was 12 weeks (range 6 to 22). Improvement in bone pain was paralleled by an improvement in the mean Karnofsky index of 45% (range 30% to 60%) to 70% (range 50% to 80%) at the end of the treatment period. Conclusions: Bisphosphonate treatment of painful osseous metastases due to hormone refractory prostate cancer results in a significant pain decrease and a significant decrease in the daily consumption of analgesics in 75% of patients. Each characteristic is paralleled by an increase in the Karnofsky index, mainly due to better mobility. Bisphosphonate should have a definite role in the palliative management of symptomatic hormone refractory prostate cancer.