Phase Ii Trial Of The Autophagy Inhibitor Hydroxychloroquine With Folfox And Bevacizumab In Front Line Treatment Of Metastatic Colorectal Cancer.

3545Background: Colorectal cancer (CRC) cells can become resistant to chemotherapy and anti-angiogenic therapy through autophagy. The antimalarial agent hydroxychloroquine (HCQ) is a potent inhibitor of autophagy, and in vivo studies in CRC cell models show significant decrease tumor volume when these autophagy inhibitors were combined with oxaliplatin and bevacizumab. We previously reported safety with HCQ 600mg BID in combination with standard front-line FOLFOX and bevacizumab in a Phase I study in metastatic CRC patients. We report the results of a single-arm phase II trial of patients with previously untreated stage IV CRC with good performance status and adequate hematologic and biochemical indices. Methods: Patients were treated with standard doses of mFOLFOX6 and bevacizumab with HCQ 600mg BID. Imaging was obtained every 2 months. Results: 37 patients were enrolled, 62% male, 89% Caucasian, median age 61, 65% ECOG PS 0, and 73% colon primary. Twenty-eight patients were evaluable for response as 2 p...