Phase I study of docetaxel (Tax) and <sup>153</sup>Sm repetitively administered for castrate metastatic prostate cancer (CMPC)
Authors: M. J. Morris, N. Pandit-Taskar, R. D. Stephenson, C. Hong, S. F. Slovin, D. Solit, D. E. Rathkopf, J. A. Carrasquillo, S. M. Larson, H. I. Scher
Journal: Journal of Clinical Oncology (2008)

5001 Background: Tax prolongs survival in patients (pts) with CMPC. Early clinical data suggest that Tax combined with bone seeking radiopharmaceuticals may improve survival relative to chemotherapy alone. 153Sm-lexidronam (Sm) (Quadramet, Cytogen Corp.) is a radiopharmaceutical with a 46.3 hour T1/2 and a favorable toxicity profile. Methods: Pts with progressive CMPC are treated in cohorts of 3–6. Prior treatment with taxanes is permissible. Cohorts are defined by dose escalations of: Tax 65, 70, 75, 75, 75 mg/m2 and Sm 0.5, 0.5, 0.5, 0.75, 1 mCi/kg. Each cycle is 6 weeks, except cohort 6, which explores a q9 week cycle for Sm. Tax is given day 1 and 22 and Sm day -1 to 1 of each cycle. DLT is defined as cycle 1 ≥ grade 3 non-hematologic toxicity, grade 3 neutropenia that lasts for >29 days, or grade 3–4 anemia or thrombocytopenia of ≥ 5 days. Pts with an ANC of grade 0–1 or platelet count (PLT) of >100,000/mm3 at the end of cycle 1 may receive additional cycles. Pts are treated until progression or toxicity. Results: 28 pts have received 81 cycles (mean 2.9, range 1–6/pt) in 6 cohorts to date. 6 pts were treated in cohorts 2, 5, and 6. As anticipated, toxicities have primarily been hematologic (Table 1). Six pts came off study for prolonged thrombocytopenia; to date, 3 have not recovered. 1 pt in cohort 6 experienced a DLT (neutropenic fever). Mean baseline PSA was 262 ng/ml with 13/28 (46%) pts achieving ≥ 50% decline in PSA. Conclusions: Coadministration of Tax and Sm has been well tolerated even with full doses of both drugs; repetitive dosing is feasible. MTD has not been reached; repetitive full doses of each drug are being tested in an expansion of Cohort 6 (12 patients) to explore the optimal dose and schedule in preparation for phase II. Support: Cytogen, Inc., NIH CA102544 Cycle 1** (n=28 pts; 28 cycles) All Cycles** (n=28 pts; 81 cycles) Median nadir ANC [K/mcl] 0.5 (0.1 - 1.7) 0.3 (0.1 - 1.3) Avg # of occurrences of ANC ≥ grade 3 per cycle 1.8 (49 occurrences/ 28 cycles) 1.9 (152 occurrences/ 81 cycles) Median days to ANC recovery* of pts with nadir ANC ≥ grade 3 7 days (3 - 15) 7 days (4 - 15) # pts who did not recover ANC to allow recycling 0/28 pts 0/28 pts Median nadir PLT [K/mcl] 118 (51 - 183) 80 (8 - 172) Avg # of occurrences of PLT ≥ grade 2 per cycle 0.1 (3 occurrences/ 28 cycles) 0.8 (64 occurrences/ 81 cycles) Median days to PLT recovery of patients whose PLT dropped below 100 K/mcL * 7 days (2 - 44) 9 days (2 - 126) Number of patients whose PLT did not drop below 100 K/mcL 19/28 pts 10/28 pts # pts who did not recover PLTS to allow recycling 0/28 6/28 * Counts sufficient to allow pts to recycle without dose reduction; ** Each cycle consists of 2 or 3 chemotherapy doses depending on the cohort Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Cytogen, sanofi-aventis