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Clinical trials designed to block autophagy in multiple cancers show promise
Date:5/22/2014

stoma multiforme

These data from a national trial with 92 glioblastoma patients established that autophagy inhibition is achievable with HCQ; however, toxicity prevented escalation to higher doses. Therefore, a definitive test of the role of autophagy inhibition in the adjuvant setting for glioma patients awaits the development of lower-toxicity compounds for optimal inhibition. No significant improvement in overall survival was observed.

Trial #2: Phase I trial of HCQ with dose-intense temozolomide in patients with advanced solid tumors and melanoma

A trial with 40 patients (73 percent with metastatic melanoma) showed that high-dose HCQ and the oral chemotherapy drug temozolomide is safe and tolerable, and is associated with autophagy inhibition. Prolonged stable disease and responses observed in about 20 percent of the patients suggests antitumor activity.

Trial #3: Combined autophagy and proteasome inhibition: A phase 1 trial of HCQ and bortezomib in patients with relapsed/refractory myeloma

A phase I trial with 25 patients combining bortezomib and HCQ for relapsed or refractory myeloma achieved autophagy inhibition and was tolerated. Of 22 patients evaluable for response, 3 (14 percent) had very good partial responses, 3 (14 percent) had minor responses, and 10 (45 percent) had a period of stable disease.

Trial #4: Combined mTOR and autophagy inhibition: Phase I trial of HCQ and temsirolimus in patients with advanced solid tumors and melanoma

This study of 27 patients indicates that temsirolimus, an mTOR inhibitor, and HCQ is safe and tolerable, blocks autophagy, and had significant antitumor
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Contact: Steve Graff
stephen.graff@uphs.upenn.edu
215-349-5653
University of Pennsylvania School of Medicine
Source:Eurekalert

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