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Impact of Addition of Metformin to Abiraterone in Metastatic Castration-Resistant Prostate Cancer Patients With Disease Progressing While Receiving Abiraterone Treatment (MetAb-Pro): Phase 2 Pilot Study

Michael Mark, Dirk Klingbiel, Ulrich Mey, Ralph Winterhalder, Christian Rothermundt, Silke Gillessen Sommer, Roger Von Moos, Michael Pollak, Gabriela Manetsch, Räto Strebel & Richard Cathomas

Kurzfassung

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.
   
Zitation Mark M, Klingbiel D, Mey U, Winterhalder R, Rothermundt C, Gillessen Sommer S, von Moos R, Pollak M, Manetsch G, Strebel R, Cathomas R. Impact of Addition of Metformin to Abiraterone in Metastatic Castration-Resistant Prostate Cancer Patients With Disease Progressing While Receiving Abiraterone Treatment (MetAb-Pro): Phase 2 Pilot Study. Clin Genitourin Cancer 2019;.
   
Typ Wissenschaftlicher Artikel/Review (Englisch)
Veröffentlichungsdatum 02-01-2019
Titel der Zeitschrift Clin Genitourin Cancer
ISSN electronic 1938-0682
PubMed 30686756
DOI 10.1016/j.clgc.2018.12.009