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CHICAGO -- Adding a diabetes drug to standard treatment in metastatic castration-resistant prostate cancer (mCRPC) failed to improve outcomes, a researcher reported here.

In the trial, 66% of non-diabetic mCRPC patients treated with metformin plus docetaxel-prednisone achieved the primary endpoint of ≥50% decrease in PSA level versus 63% of patients treated with docetaxel-prednisone plus placebo (P=0.94), which was a non-significant finding, according to Marc Pujalte Martin, MD, of Centre Antoine Lacassagne, Universite Cote d'Azur in Nice, France.

Progression-free survival was 7.4 months with add-on metformin versus 5.6 months without, while overall survival came in at a median of 24.6 months versus a median of 19.6 months, respectively, he said in a presentation at the American Society of Clinical Oncology (ASCO) annual meeting.

"This is the first randomized controlled phase II trial testing the combination of metformin with docetaxel in metastatic castration-resistant prostate cancer," Pujalte Martin and colleagues stated. "The addition of metformin to docetaxel did not seem to have a meaningful clinical benefit in this setting."

However, Pujalte Martin noted that the addition of metformin did not result in any cases of hypoglycemia or in the development of unexpected adverse events (AEs).

Previous has indicated the potential for a decrease in prostate cancer incidence and mortality with metformin, which is a readily available drug that is relatively inexpensive, he explained.

For the trial, non-diabetic, chemotherapy-naive mCRPC patients (median age 70; ECOG 0-1) were assigned 1:1 to receive docetaxel (75mg/m²) every 21 days plus prednisone (5 mg) twice a day, and either metformin (850 mg) twice a day (arm A) or placebo (arm B), up to 10 cycles. From January 2013 to December 2015, 99 patients were randomized (50 in arm A; 49 in arm B) at 10 French centers, and 95 patients were evaluable. Follow-up was >40 months.

The median metformin exposure was about 145 days, and relative dose-intensity was 99%, Pujalte Martin said. The median number of cycles of docetaxel was seven, and about 37% of the patients were able to tolerate 10 cycles of docetaxel. If docetaxel was interrupted or discontinued, metformin and placebo were similarly discontinued, he added.

The authors reported no observed difference between arm A and arm B in PSA response rate (72% in both arms) or overall response rate (28% in both arms).

There also was no difference between arms in AEs, except a trend for diarrhea with metformin (70% in arm A vs 50% in arm B, P=0.072). The were few grade 3-4 adverse events.

There was no difference in quality of life according to the score between the two arms during the treatment period.

ASCO invited discussant Mary-Ellen Taplin, MD, of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute in Boston, who said that the results "should reduce off-label use of metformin. Given the high rate of grade 1 and grade 2 toxicities with metformin, which approached 70% in the context of chemotherapy, this type of treatment is not innocuous."

Pujalte Martin pointed out that the ongoing includes an arm with metformin.

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