Intermittent chemotherapy (ICh) for metastatic castration-resistant prostate cancer (mCRPC): Results of a prospective randomized phase II trial of the DoD Prostate Cancer Clinical Trials Consortium.

Abstract

133 Background: Docetaxel remains the standard of care for patients (pts) with mCRPC. However, the optimal duration of chemotherapy (Ch) is not known. Providing Ch holidays is often undertaken, but is not well characterized. A randomized phase II trial was undertaken to test two ICh regimens. Methods: Pts with Ch naive mCRPC and KPS > 60% were eligible. Pts were treated with “induction” docetaxel 75 mg/m2 q3 weeks, and prednisone 5 mg po bid. After 6 cycles, responding pts (PSAWG1 criteria) stopped Ch and were randomized to observation (Obs) or to GM-CSF, 250 mcg/m2 sq daily for 14 days out of every 28 day cycle. Pts were followed with monthly PSA and imaging every 2 cycles until progressive disease (PD) by PSAWG1 criteria, at which point they resumed treatment with Ch, again for 6 cycles, followed by the same “off Ch” regimen. The primary endpoint was the time to PD while on Ch (time to Ch resistance.) Results: Of 97enrolled pts to date, 94 are evaluable (3 are still undergoing induction). 69 pts completed induction (25 did not due to PD, adverse events (AE), or MD choice), of which 27 had PD after 6 cycles. Thus, 42/94 evaluable pts (45%) were eligible for randomization. Of these, 21 pts underwent Obs and 21 received GM-CSF. To date, 23/42 (55%) pts who underwent a Ch holiday restarted Ch, all for PSA PD. 8/23 (35%) had a response to Ch re-initiation. (15 pts did not re-start Ch because of AE, other therapy being started, or patient choice, and 4 pts are still undergoing either Obs or GM-CSF.) Obs pts were “off Ch” for a median of 2 months (range 2-4), compared with 3 months (range 2-8) for GM-CSF pts. Conclusions: While feasible, only 45% of pts met criteria for ICh. 35% of pts responded to Ch re-initiation. Insufficient data exist to assess the impact of GM-CSF on time off Ch or time to Ch resistance. No significant financial relationships to disclose.