A phase II study of imatinib mesylate in prostate cancer patients with evidence of biochemical relapse following definitive radical retropubic prostatectomy or radiation therapy

Abstract

3092 Background: Biochemical recurrence of prostate cancer after definitive or salvage local therapy in the absence of metastatic disease represents a group of men well suited for a novel therapeutic intervention. Imatinib mesylate (Gleevec) is a protein-tyrosine kinase inhibitor which has previously been tested in men with androgen-independent and metastatic prostate cancer. This phase II study was undertaken to determine the safety and efficacy of imatinib mesylate in men with biochemical relapse of non-metastatic, androgen-sensitive prostate cancer following local therapy. Patients and Methods: Twenty-seven patients were treated with imatinib mesylate 400mg twice daily for 12 months or until evidence of disease progression or dose limiting toxicity. All patients had evidence of biochemical progression with a rising PSA after definitive radiation therapy, prostatectomy, or prostatectomy and salvage radiation therapy. Three patients (11%) completed less than 4 weeks of therapy and were not evaluable. Results: Of the 24 patients evaluated for a biochemical response, six patients (22%) demonstrated a stable PSA over the course of treatment; two patients (7%) experienced a partial response to treatment as defined by a PSA decline of greater than 50% for at least 4 weeks duration. Duration of response in these two patients was 5 months and 12 months. Sixteen patients (59%) demonstrated progressive disease as defined by a 25% or greater increase in PSA above the baseline value at study entry. There was no association between overall PSA response and changes in serum testosterone level. The proportion of patients achieving a partial response in PSA while on therapy did not significantly differ from the null rate of 5% using a two-sided exact binomial test (P=0.394; 95% CI 0.9% - 24.3%). There was no irreversible NIH-CTC Grade 3 or 4 toxicities. Grade 3 and 4 toxicity included leukopenia (3.7%), elevation in SGOT (7.4%) and SGPT (7.4%), and rash (18.5%). Conclusions: Imatinib mesylate delivered at a dose of 400mg twice daily is associated with acceptable toxicity and limited ability to confer a PSA response in this patient population. No significant financial relationships to disclose.