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YM155 Shows Indication of Usefulness in Cancer

Drug inhibits survivin, which in turn is inhibitor of apoptosis; survivin expressed in most malignancies

THURSDAY, Oct. 2 (HealthDay News) -- YM155, which inhibits the antiapoptosis protein survivin -- a current target of interest for cancer therapy -- appears to offer antitumor activity, according to the results of a phase I and pharmacokinetic study published online Sept. 29 in the Journal of Clinical Oncology.

Anthony W. Tolcher, M.D., of South Texas Accelerated Research Therapeutics in San Antonio, Texas, and colleagues analyzed data from 41 adults with solid malignancies that were refractory to medical therapy, predominantly prostate and colorectal cancer, non-Hodgkin's lymphoma, and sarcoma. Escalating doses of YM155 were given via continuous intravenous infusion over 168 hours. Patients received a median number of three cycles, with dosages ranging from 1.8 to 6.0 mg/m2.

Three out of five patients with non-Hodgkin's lymphoma had complete or partial responses lasting eight to 48 months or longer, and two of nine patients with prostate cancer had a response by prostate-specific antigen criteria, the authors write. The main toxicities were short-term stomatitis, as well as pyrexia, nausea and arthralgia; most toxicities were grades 1 and 2, the report indicates.

"Given the nature of phase I studies, statistical comparisons are impossible for tumor response results. However, a 12.1 percent response rate in this phase I study with YM155 seems robust compared with other studies," write the authors of an accompanying editorial. "The fact that survivin is a nodal protein linking multiple pathways of cellular homeostasis makes YM155 an attractive drug to combine with other agents."

The study was supported by Astellas Pharma US. Tolcher and several co-authors disclosed financial relationships with the company, and an editorial author listed other disclosures.

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