Gastrointestinal and genitourinary toxicity profiles of metformin versus placebo in men with prostate cancer receiving prostate radiotherapy: interim toxicity results of a double-blinded, multicenter, phase II randomized controlled trial

Radiation Oncology

Sunita Ghosh¹  Lindsay Rowe²  Brita Danielson²  Nawaid Usmani²  Don Yee²  Matthew Parliament²  Harvey Quon³  Megan O. McDonald⁴  Shahida Ahmed⁵  Arbind Dubey⁵  Rashmi Koul⁵  Aldrich Ong⁵  Julian O. Kim⁶  William Hunter⁷  Gokulan Sivananthan⁷ 

[1] Department of Oncology, University of Alberta, Edmonton, Alberta, Canada;Division of Radiation Oncology, Department of Oncology, University of Alberta, Edmonton, Alberta, Canada;Division of Radiation Oncology, Department of Oncology, University of Calgary, Calgary, Alberta, Canada;Postgraduate Medical Education, Max Rady Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada;Radiation Oncology, Department of Radiology, Max Rady Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada;Radiation Oncology, Department of Radiology, Max Rady Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada;CancerCare Manitoba Research Institute, CancerCare Manitoba, 675 McDermot Ave, R3E 0V9, Winnipeg, Manitoba, Canada;Radiation Oncology, Department of Radiology, Max Rady Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada;Western Manitoba Cancer Center, Brandon, Manitoba, Canada;

关键词: Metformin;    Prostate cancer;    Gastrointestinal toxicity;    Genitourinary toxicity;   

DOI  :  10.1186/s13014-021-01935-x

来源: Springer

【 摘 要 】

Androgen deprivation therapy (ADT) used for prostate cancer (PCa) management is associated with metabolic and anthropometric toxicity. Metformin given concurrent to ADT is hypothesized to counteract these changes. This planned interim analysis reports the gastrointestinal and genitourinary toxicity profiles of PCa patients receiving ADT and prostate/pelvic radiotherapy plus metformin versus placebo as part of a phase 2 randomized controlled trial. Men with intermediate or high-risk PCa were randomized 1:1 to metformin versus placebo. Both groups were given ADT for 18–36 months with minimum 2-month neoadjuvant phase prior to radiotherapy. Acute gastrointestinal and genitourinary toxicities were quantified using CTCAE v4.0. Differences in ≥ grade 2 toxicities by treatment were assessed by chi-squared test. 83 patients were enrolled with 44 patients randomized to placebo and 39 randomized to metformin. There were no significant differences at any time point in ≥ grade 2 gastrointestinal toxicities or overall gastrointestinal toxicity. Overall ≥ grade 2 gastrointestinal toxicity was low prior to radiotherapy (7.9% (placebo) vs. 3.1% (metformin), p = 0.39) and at the end of radiotherapy (2.8% (placebo) vs 3.1% (metformin), p = 0.64). There were no differences in overall ≥ grade 2 genitourinary toxicity between treatment arms (19.0% (placebo) vs. 9.4% (metformin), p = 0.30). Metformin added to radiotherapy and ADT did not increase rates of ≥ grade 2 gastrointestinal or genitourinary toxicity and is generally safe and well-tolerated.

【 授权许可】

CC BY