Phase I study of interleukin 2 (IL2) maintenance after induction with weekly docetaxel and estramustine in patients with metastatic hormone refractory prostate cancer (HRPC)

Abstract

14526 Background: Patients with HRPC commonly respond to docetaxel, but many develop asthenia and other docetaxel related toxicities that impair quality of life and hence, many clinicians prescribe a “chemotherapy vacation”. IL2 exerts its anti-tumor effect through activation of T cells and NK cells and at high dose has been shown to have efficacy (and toxicity) in men with HRPC (Maffezzini, The Prostate 1996). Low dose IL2 and 13-cis-retinoic acid given as maintenance after cytoreduction of advanced solid tumors was associated with increased numbers of circulating NK cells as well as further tumor responses (Recchia, Proc ASCO 2001). A phase I trial of low dose IL2 maintenance after chemo induction was undertaken. Methods: Chemotherapy naive pts with metastatic HRPC were induced with weekly docetaxel 35 mg/m2 on day 2 and estramustine 280 mg/M2 TID on days 1 and 2 for 3 wks followed by 1 wk off for a total of 12 doses of chemotherapy. Responding pts received maintenance IL2 for 5 days/wk for 3 wks, followed by 1 wk off. During the 3rd wk, a boost dose was administered on days 2 and 3. Level 1 maintenance was 0.5 x106 IU/m2 SC bid, level 2 was 0.75 × 106 IU/m2 SC bid. Level 1 boost was 3 × 106 IU/m2, level 2 was 4.5 × 106 IU/m2 SC bid. Cohorts of 3 patients were treated at a given dose level according to standard dose escalation schemes for toxicity. IL2 was continued until objective progression was documented. Results: 15 pts, median age of 70 (range 46–78), median PSA 32.7 (range 2.28 to 1248) were enrolled. After chemotherapy, 12 pts had > 50% (7 had > 75%) decline in PSA, 3 pts had < 50% decline. 13 pts went on to receive IL2. The MTD for maintenance IL2 was 0.5 × 106 IU/m2 SC bid (4 pts at level 1 had no toxicity but 3 of 4 at level 2 had grade 2 toxicity requiring a drop to level 1). MTD for the boost was 3 × 106 IU/m2 (4 with no toxicity at level 1, 3 of 3 with grade 2 toxicity at level 2 requiring a drop to level 1). The most common toxicities were fatigue, nausea, chills, edema. One pt has received IL2 maintenance for 25 months. Conclusions: IL2 maintenance can be safely administered at the MTD. Immunological studies before/after chemotherapy and during IL2 are pending. No significant financial relationships to disclose.