A phase I open-label study using lenalidomide and docetaxel in castration- resistant prostate cancer

Abstract

5156 Background: Based on efficacy of docetaxel (D) and possible synergism with antiangiogenic agents in AIPC demonstrated by results from a NCI trial of D ± thalidomide, a phase I trial evaluating escalating doses of D and lenalidomide (Ln), a derivative of thalidomide with immunomodulatory and antiangiogenic properties, was designed. Methods: Eligibility requirements include progressive measurable disease or rising PSA levels after antiandrogen withdrawal and < 2 prior chemotherapy regimens. All patients were required to have a castratete testosterone <50 ng/dl and to continue medical castration. Dose of D was 60 mg/m2 on Day 1 of 21-day cycle for dose level (L)1 and 75 mg/m2 for L 2–6. Ln dose levels were: 10 mg (L1–2), 15 mg (L3), 20 mg (L4), 25 mg (L5) and 30 mg (L6) for days #1–14. Pts were given prednisone 5 mg po |[BI]D continuously and 8 mg of decadron 12, 8 and 1 hour prior to D without prophylactic anticoagulation. 6 patients (pts) were entered at each level, escalation to the next level occurred if no more that 1 dose limiting toxicity|[(D]LT) was observed during cycle 1. Results: Thirty four pts were enrolled in L1–6; all pts are evaluable for toxicity. Pt characteristics include median age of 70 yrs (range 47–85), median baseline PSA of 101.9 ng/ml (range 5.9–7480), 14 pts (41%) had received prior chemotherapy (7 with 2 prior regimens). All had overt metastatic disease to viscera or bone; 21 pts had measurable disease. Median number of cycles for L1-L5 was 8 (range 2–19). DLT's observed: L2: Grade 4 Neutropenia (1 pt); L3–5 None. Of the 3 patients treated at L6, 2 developed DLTs (febrile neutropeina, grade 4 neutropenia) precluding further dose escalation. Other Grade 3/4 toxicities observed after cycle 1 included deep venous thrombosis (2 pts), grade 3 neutropenia (2 pts), grade 3 facial edema (1 pt) Of 31 pts evaluable for post treatment PSA declines; 8/17 (47%) untreated pts 7/14 (50%) previoustly treated pts had a >50% decline in PSA. Five pateints achieved a partial response in measurable disease, one had a near complete resolution of a biopsy proven metastatic pulmonary nodule. Conclusions: The recommended dose for is 75 mg/m2 D Q 3 weeks day 1 and Ln 25 mg PO D1–14. An expanded cohort of 10 patients will be treated at this level to further define toxicities. No significant financial relationships to disclose.