An open-label study of the safety and tolerability of pazopanib in combination with FOLFOX6 or CapeOx in patients with colorectal cancer
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Background Although combining targeted agents with conventional, first-line cytotoxic therapy has improved survival outcomes in patients with advanced colorectal cancer, further improvements in outcomes and tolerability are needed. Methods This phase I study evaluated the feasibility of combining oral pazopanib, an agent that targets multiple proangiogenic factors, with FOLFOX6 (oxaliplatin, leucovorin, and 5-fluorouracil) or CapeOx (oxaliplatin and capecitabine). This phase I study evaluated the optimally tolerated regimen of daily pazopanib (dose-escalated) plus standard FOLFOX6 or CapeOx in patients with advanced colorectal cancer. At the optimally tolerated regimen, each cohort was expanded to further evaluate safety and clinical response. Results The optimally tolerated regimens were pazopanib 800 mg plus FOLFOX6 and pazopanib 800 mg plus reduced CapeOx (capecitabine 850 mg/m2). The most commonly reported adverse events in the FOLFOX6 cohorts included decreased appetite, neutropenia, diarrhea, peripheral neuropathy, and vomiting. Similarly, the most commonly reported adverse events in the CapeOx cohorts included fatigue, vomiting, and decreased appetite. The overall response rate was 40 % (8/20 patients) in the pazopanib plus FOLFOX6 cohorts and 38 % (8/21 patients) in the pazopanib plus CapeOx cohorts. Conclusion Pazopanib combined with FOLFOX6 or reduced CapeOx was adequately tolerated in this patient population.
KeywordsCapeOx Colorectal cancer Dose escalation FOLFOX6 Pazopanib
The authors thank Jerome F. Sah, PhD, of ProEd Communications, Beachwood, Ohio, for his medical editorial assistance with this manuscript. The authors also would like to acknowledge Theresia Peckham of Trio Clinical Research, LLC, Raleigh, North Carolina, for her contributions to the conduct of the study and to the initial draft of the manuscript, and Medical Monitors Jo Lager, MD (formerly of GlaxoSmithKline), and Derry Ridgeway, MD, of SRA International, Merced, California.
This study was sponsored by GlaxoSmithKline Pharmaceuticals, Philadelphia, Pennsylvania. Financial support for medical editorial assistance was also provided by GlaxoSmithKline. Dr. Midgley acknowledges research support from the United Kingdom Department of Health (DH) Higher Education Funding Council for England (HEFCE) and Oxford National Institute for Health Research (NIHR) Biomedical Research Centre. Dr. Brady acknowledges research support from Cancer Research UK and the Experimental Cancer Medicine Centre. Dr. Chau would like to acknowledge National Health Service funding to the National Institute for Health Research Biomedical Research Centre.
Conflict of Interest Disclosure
J. Brady, P. Corrie, R. Digumarti, and R.S. Midgley report no potential conflict of interest. I. Chau has received honoraria from Roche and has served on advisory boards for Roche and Merck Serono. M. Mallath reports current research sponsored by GlaxoSmithKline Pharmaceuticals and participation in speakers bureaus for Roche and Dr. Reddy’s Laboratories. L. Adams and K. Laubscher are currently employed by GlaxoSmithKline and hold company stock positions. J. Botbyl is a paid statistical consultant for GlaxoSmithKline.
This study was conducted in compliance with the current laws of the countries (United Kingdom and India) in which it was conducted.
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