Phase I trial with a combination of docetaxel and 153Sm- EDTMP in patients (pts) with castration-resistant metastatic prostate cancer (mCRPC)

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5155 Background: Bone targeted therapy holds great promise for improving outcomes in mCRPC. Preclinical data strongly supported biological synergism of docetaxel (Tax) and 153Sm-EDTMP (Sm) in mCRPC. Concurrent Tax and Sm regimens were reported feasible and tolerable in phase I studies. This study was designed to evaluate toxicity and preliminary efficacy of 2 cycles (12 wks/cycle, C) of concomitant standard dose/schedule of Sm plus Q3 wks schedule of Tax in mCRPC. Methods: mCRPC pts with progressive bone metastases were treated in 4 cohorts ( CH). Previous Tax and palliative RT to bone was admissible. Dose escalation of Tax was implemented if no DLT was observed in the preceding CH. Tax doses (on days 1, 22, per 12 wk cycle) were given as follows: CH 1- 50mg/m2 (C1 and 2); CH 2–75mg/m2 (C1) and 50mg/m2 (C2); CH3 - 75mg/m2 (C1 and 2) and CH4 ( Tax day 1, 22, 43 per 12 wk C) 75mg/m2 (C1 and 2). Sm was administered on days 2 (Q12 wks X 2) at dose of 1 mCi/kg/cycle (max. of 2 cycles). Disease status was assessed (with bone /CT scans and PSA) after every cycle. Results: Thirteen pts with progressive bone metastases were enrolled. Three had prior Tax and 3 had prior palliative radiation. Thirteen pts received total 20 cycles in 4 cohorts. Toxicity was primarily hematological. There were total 34 episodes Grade 3/4 neutropenia with a median 7 (range 7 -14) days to recovery to ≤ grade1. Tax dose was reduced to 50% in 2 CH4 pts at C2. Only 1 DLT G3 thrombocytopenia occurred on cohort 4 with duration of 9 wks. Median baseline PSA was 100.4 ng/ml (range 8.6 - 1064), 9/13 (69%) pts had PSA>50% decrease. Median time to disease progression was 147 days (range 72 days - 10 months+); 6/13 (46%) pts had stable/improved bone scans at 6 months and 8/8 (100%) symptomatic pts had improvement in pain. Conclusions: Concurrent 6-month administration of 2 and possibly 3 full dose /standard schedule of Tax with 2 full doses of Sm is feasible with reversible bone marrow suppression. The combination may provide additional clinical benefits for mCRPC pts with extensive bone metastasis. No significant financial relationships to disclose.