Abstract
Background
There is evidence linking metformin to improved prostate cancer–related outcomes.
Patients and Methods
Twenty-five men with metastatic castration-resistant prostate cancer and prostate-specific
antigen (PSA) progression while receiving treatment with abiraterone from 3 Swiss
centers were included in this single-arm phase 2 trial between November 2013 and September
2016. Metformin was added to abiraterone continuously at 1000 mg twice daily in uninterrupted
4-week cycles. The primary end point was the absence of disease progression at 12
weeks (PFS12). The Fleming single-stage design was applied. With a 5% significance
level and 80% power, 25 patients were required to test PFS12 ≤ 15% (H0) compared to ≥
35% (H1). Secondary end points included toxicity and safety issues. The study was
registered at ClinicalTrials.gov (NCT01677897).
Results
The primary end point PFS12 was 12% (3 of 25 patients) (95% confidence interval, 3-31).
Most patients had PSA progression, almost half had radiographic progression, but only
1 patient had symptomatic progression. Eleven (44%) of 25 patients had grade 1 and
2 patients each grade 2 (8%) or grade 3 (8%) gastrointestinal toxicity (nausea, diarrhea,
loss of appetite). One patient discontinued treatment at week 5 because of intolerable
grade 3 diarrhea.
Conclusion
The addition of metformin to abiraterone for patients with metastatic castration-resistant
prostate cancer and PSA progression while receiving abiraterone therapy does not affect
further progression and has no meaningful clinical benefit. A higher-than-expected
gastrointestinal toxicity attributed to metformin was observed.
Keywords
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Article info
Publication history
Published online: January 02, 2019
Accepted:
December 26,
2018
Received in revised form:
December 23,
2018
Received:
October 29,
2018
Identification
Copyright
© 2018 Elsevier Inc. All rights reserved.
