AIM: This study aimed to evaluate the safety, pharmacokinetics and treatment effects of an alpha(nu)beta(3) 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.
RCT Entities:
AIM: This study aimed to evaluate the safety, pharmacokinetics and treatment effects of an alpha(nu)beta(3) 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.
Authors: Jihong Li; Yoshiyuki Fukase; Yi Shang; Wei Zou; José M Muñoz-Félix; Lorena Buitrago; Johannes van Agthoven; Yixiao Zhang; Ryoma Hara; Yuta Tanaka; Rei Okamoto; Takeshi Yasui; Takashi Nakahata; Toshihiro Imaeda; Kazuyoshi Aso; Yuchen Zhou; Charles Locuson; Dragana Nesic; Mark Duggan; Junichi Takagi; Roger D Vaughan; Thomas Walz; Kairbaan Hodivala-Dilke; Steven L Teitelbaum; M Amin Arnaout; Marta Filizola; Michael A Foley; Barry S Coller Journal: ACS Pharmacol Transl Sci Date: 2019-08-02
Authors: Mark Sutherland; Andrew Gordon; Steven D Shnyder; Laurence H Patterson; Helen M Sheldrake Journal: Cancers (Basel) Date: 2012-10-26 Impact factor: 6.639
Authors: Xiaoyan Zhou; Ji Zhang; Robin Haimbach; Wei Zhu; Rosemary Mayer-Ezell; Margarita Garcia-Calvo; Elizabeth Smith; Olga Price; Yanqing Kan; Emanuel Zycband; Yonghua Zhu; Maarten Hoek; Jason M Cox; Lijun Ma; David E Kelley; Shirly Pinto Journal: Pharmacol Res Perspect Date: 2017-10