Bristol-Myers Squibb Company has announced interim results from two Phase II studies of SPRYCEL(R) (dasatinib) which demonstrate that the medicine may have potential as a treatment for a certain type of advanced prostate cancer. The data will be presented in totality at the American Society for Clinical Oncology (ASCO) annual meeting to be held May 29 to June 2 in Orlando, Florida. SPRYCEL is currently indicated for the treatment of adults with resistance or intolerance to prior therapy for chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). The Phase II studies (CA180-085 and CA180-086) to be presented at ASCO focus on SPRYCEL’s potential as a treatment for castrate-resistant prostate cancer (CRPC). Data from these studies support the rationale for the ongoing global Phase III study (CA180-227) of men with CRPC treated with the combination of SPRYCEL and the current standard of care docetaxel. This ongoing Phase III study is currently recruiting patients in the United States, Mexico, Australia, Canada, South Africa and countries in Europe, Asia and South America. Additional information about the study is available at www.clinicaltrials.gov. “These preliminary results are promising as we continue to fully develop SPRYCEL for a number of life-threatening tumor types,” said David Shapiro, M.D., vice president, Sprycel development team at Bristol-Myers Squibb. “SPRYCEL is the most clinically advanced SRC inhibitor with demonstrated efficacy and safety in patients with solid tumors.” In a single-agent study (CA180-085) examining three dosing regimens of SPRYCEL in CRPC patients, preliminary clinical activity (tumor and prostate-specific antigen response; decreasing bone turnover) was similar in patients receiving once-daily or twice-daily SPRYCEL schedules. In an add-on study with docetaxel (CA180-086), the combinations were shown to be well tolerated with no drug-drug interactions observed. Further encouraging clinical activity was also reported. Most common Grade 1 or 2 adverse events in the CRPC studies included fatigue, headache, diarrhea and nausea. Grade 3 or 4 adverse events included asthenia, dyspnea and three cases of pleural effusion. In preclinical models, SRC and related kinases (SRC family kinases (SFK)) have been identified as central mediators in oncogenic, invasive and bone metastatic processes and are a potential therapeutic target in solid tumors. Given its central role in these processes, SRC kinase inhibition may have the potential for broad therapeutic activity in patients with SRC-dependent cancers. “Our clinical trial program is focused on tumor types where SRC and SFK play a central role in promoting tumor growth and metastasis,” said Dr. Shapiro. “To effectively treat CRPC,a comprehensive targeted approach is needed that affects both the tumor and the bone microenvironment.”
