Evaluation of the safety,pharmacokinetics and treatment effects of an ανβ3 integrin inhibitor on bone turnover and disease activity in men with hormone‐refractory prostate cancer and bone metastases

Aim: This study aimed to evaluate the safety, pharmacokinetics and treatment effects of an α_νβ₃ integrin inhibitor on bone turnover and disease activity in men with hormone‐refractory prostate cancer (HRPC) and bone metastases. Methods: A total of 21 patients with bone metastases and HRPC were randomized to receive MK‐0429 200 mg b.i.d. or 1600 mg b.i.d. for 4 weeks. Toxicity, pharmacokinetics and markers of bone turnover and tumor activity were examined. Results: Nausea was the most common adverse event: one (200‐mg group) and 11 (1600‐mg group) patients. At 4 weeks, mean AUC_{0–12 h} was 210 mmol*h (200‐mg group) and 673 mmol*h (1600‐mg group); mean C_max values were 42 mmol/L (200‐mg group) and 154 mmol/L (1600‐mg group). Urinary cross‐linked N‐telopeptides of type I collagen to creatinine ratio (uNTx), a bone turnover biomarker, showed a change from baseline of ?43.4 percent (200‐mg group) and ?34.1 percent (1600‐mg group). There was an increase in serum prostate specific antigen (PSA), a marker for disease activity, of 54.1 percent (200‐mg group) and 44.5 percent (1600‐mg group). Conclusion: MK‐0429 was generally well tolerated, with the most common side‐effect being nausea. There was some evidence of an early reduction of bone turnover, indicating a potential for clinical use in the treatment of MBD although serum PSA was unexpectedly increased during the study.