Phase I trial of docetaxel (D) plus samarium153 (Sm 153) in patients (pts) with hormone refractory prostate cancer (HRPC)

Abstract

15547 Background: Bone targeted approaches hold great promise for improving outcomes in HRPC. Docetaxel (D) and samarium 153 (Sm153 ) have individually demonstrated a clinical benefit and preclinical data strongly support biological synergism in HRPC. Preclinical data suggests that 24 hour after a dose of D, there is maximum G2M arrest. This results in the accumulation of cells in the most radiosensitive phase of the cell cycle. This phase I trial was designed to evaluate toxicity and preliminary efficacy of combined D and Sm153 administered sequentially in advanced HRPC. Methods: HRPC pts progressing after anti-androgen withdrawal; = 2 prior chemotherapy regimens; acceptable bone marrow, renal and hepatic function were eligible. Planned D treatment in 4 cohorts (N=3/cohort) includes: Cohort 1: D 50mg/m2 IV on days 1, 22, 91, and 112; cohort 2: D 75mg/m2 IV on days 1 and 22 followed by 50mg/m2 IV on days 91 and 112; cohort 3: D 75mg/m2 IV on days 1 and 22 followed by 75mg/m2 IV on days 91 and 112; cohort 4: D 75 mg/m2 IV on days 1, 22, 42, 91, 112, and 133. Sm 153 (1.0 mi/Kg) is administered IV days 2 and 92 of each cycle. Cycles are repeated Q 12 wks (max 2 cycles). The endpoint for this trial is dose limiting toxicity and maximal tolerated dose. Results: From 5/11/05 - 1/7/07 ten pts were enrolled. Median: age 69.5 yrs (range 58–76), ECOG performance status 1 (range 0–1), baseline PSA 76.65 ng/ml (range 9.6–1064 ng/ml ), prior hormonal manipulations 3 (range1–6). Three pts had prior taxotere and 3 pts had prior palliative RT. All had bone metastases and 2 also had soft tissue disease. Five pts completed 2 cycles of treatment as planned. Five pts had 1 cycle (one pt is on treatment, 3 pts had PD and 1 had prolonged grade 1 thrombocytopenia =3 wks). Nine of 10 pts had reversible grade 3 / 4 neutropenia (1 pt had reversible episode of neutropenia with fever). Seven of 7 symptomatic pts had improvement in pain. Four of 10 of pts had a 50 % decline in PSA level lasting = 4 weeks; no soft tissue disease responses. Conclusions: Our preliminary data suggest that Q 3 wk D and Q 3 month Sm153 may be administered simultaneously at full doses in extensively pretreated HRPC pts, with acceptable toxicity and significant activity. This study is supported by a grant from sanofi- aventis and Sm153 is provided by Cytogen. No significant financial relationships to disclose.