Preoperative platelet-derived growth factor receptor inhibitor therapy combined with docetaxel and androgen ablation in high-risk localized prostate cancer

Abstract

5141 Background: Reduction in tumor interstitial fluid pressure with platelet-derived growth factor receptor (PDGFR) inhibitor therapy in experimental systems improves drug delivery and the therapeutic index of taxane chemotherapy (Pietras, Cancer Research, 2002). We hypothesized that PDGFR inhibitor therapy with imatinib mesylate combined with androgen ablation (AA) and docetaxel (D) induces pathological complete responses (pCR) in high-risk localized prostate adenocarcinoma (PC) prior to radical prostatectomy and pelvic lymph node dissection (RP). Methods: Thirty six men with PC ≥T2 disease or Gleason grade 8–10 or serum prostate-specific antigen (PSA) > 20 ng/ml or cT2b and PSA >10 ng/ml and Gleason 7 disease (AJCC, 1992), without radiological evidence of metastases, were planned to receive intramuscular leuprolide, imatinib 600mg orally daily, and weekly D 30 mg/m2 on D1, 8, 15, 22 q42 for three cycles (18 weeks) before RP [β (0.02, 1.98) prior on the possibility of pCR]. Unresectable pelvic nodal disease, post-operative PSA > 0.2 ng/ml or administration of post-operative radiation or AA were defined as treatment failure. Results: Between 6–03 and 9–04, 39 men were registered; median age 57 years (range, 44–71); 35 Caucasian, 2 Hispanic, 4 African-American. Risk factors included T3 disease (22/39), Gleason 8–10 disease (31/39), PSA > 20 ng/ml (12/39). Three men were ineligible or declined therapy; 29/36 (80%) received three cycles of therapy; 7/36 (20%) discontinued therapy related to toxicity. Grade 3–4 toxicity included rash (n=3), diarrhea (n=5), fatigue (n=3), neutropenia (n=2), hepatic (n=1). Severe or unexpected surgical complications were not encountered. No pCRs were defined; 15/36 (42%) have PSA < 0.2 ng/ml [12/36 (33%), <0.1 ng/ml] at 24 months and 13/36 (36%) met definition for treatment failure. Conclusions: The addition of the PDGFR inhibitor imatinib to pre-operative AA and D, although feasible, did not induce pCR in PC. [Table: see text]