A phase II evaluation of imatinib mesylate (G) in stage M0 prostate cancer (PC) patients (pts) on hormonal therapy (HT) with evidence of biochemical relapse

Abstract

14612 Background: Imatinib mesylate (Gleevec, G) is a potent inhibitor of the tyrosine kinases and other signaling mediated events. Preclinical models suggest that G inhibits platelet derived growth factor (PDGF) and stem cell factor (SCF) which are important for prostate cancer growth. This trial was designed to evaluate the safety and efficacy of G in PCA pts on HT with stage M0 disease. Methods: Eligible PCA pts included: stage M0 disease with rising PSA levels while on hormonal therapy, no prior chemotherapy. Planned treatment included G 400 mg PO BID given up to a maximum of 12 months. The statistical endpoint for this trial was the% of pts with a ↓ in prostate specific antigen (PSA) ≥ 50% lasting ≥ 4 wks. A 2 stage trial was designed where the study would terminate if the% of pts meeting the endpoint was not convincingly > 30% with 5% chance for error. Pts with a > 50% rise in PSA from baseline were removed from study. Follow-up included monthly toxicities and PSA (specimens frozen/stored until completion of each 3 months of therapy). Results: From 10/1/02–10/11/04, nine pts were enrolled. Pt characteristics included median: age of 67 years (range 52–80), ECOG performance status of 0 (range 0–1), baseline PSA of 29.6 ng/ml (range 2.69–39.52), # prior hormonal manipulations of 3 (1–5). Prior local therapies included: 1 status post (s/p) RP alone, 2 s/p RT alone, 2 s/p neoadjuvant HT plus RP, 2 s/p neoadjuvant HT plus RT. Two pts had no prior local therapy. Two pts had prior salvage RT, 1 had prior palliative RT. Eight of 9 pts evaluable for response and toxicity. One patient never received treatment. None of the pts had a decline 50% decline in PSA level lasting ≥ 4 weeks. Three of 8 pts (38%) had rapid increases in PSA and 4/8 pts (50%) developed metastatic disease after 3 months of therapy. Only one pt completed 12 months of planned therapy. Grade 3/4 toxicities included: fatigue (25%), rash (25%), arthralgias (12.5%), peripheral edema (25%), depression (12.5%), necessitating dose delays and/or discontinuation of G in 4/8 pts (50%). Conclusions: These data suggest significant toxicity and low clinical benefit. Further evaluation of Gleevec in this pt population is not warranted. No significant financial relationships to disclose.