Phase II Trial Reveals Sarcoma mTOR Inhibitor May Improve Outcomes for Some Patients

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As reported in Cancer Therapy Advisor by John Schieszer, a Phase II trial led by an investigator at Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University and colleagues, found that adding an mTOR inhibitor to chemotherapy may help improve outcomes in the treatment of sarcomas. The study results were recently published I the journal Clinical Sarcoma Research. Previous studies had suggested the addition of an mTOR inhibitor to chemotherapeutic agents was beneficial in sarcoma; however, now researchers are proposing a mechanism by which mTOR inhibition enhances the efficacy of chemotherapy. As reported in Clincialtrials.gov the study’s sponsor was Johns Hopkins, and collaborators included Pfizer (Wyeth).

The researchers found that the median progression-free survival (PFS) was 315 days (range, 27 days to 799 days). The overall response rate, which was defined as stable disease or better, was 53 percent at 60 days. In this cohort, nine patients previously had been treated with doxorubicin. The study showed this combination therapy was well tolerated. Some patients had pretreatment and posttreatment tumor biopsies, and the researchers found a correlation between response and decreased aldehyde dehydrogenase (ALDH) expression, and a correlation between biopsy-proven inhibition of mTOR and response.

A sarcoma is cancer that arises from transformed cells of mesenchymal (connective tissue) origin. Thus, malignant tumors made of cancellous bonecartilagefatmusclevascular, or hematopoietic tissues are, by definition, considered sarcomas. This is in contrast to a malignant tumor originating from epithelial cells, which are termed carcinoma. Human sarcomas are quite rare. Common malignancies, such as breastcolon, and lung cancer, are almost always carcinoma.