Phase II study of imatinib mesylate in patients with prostate cancer with evidence of biochemical relapse after definitive radical retropubic prostatectomy or radiotherapy.
OBJECTIVE
Patients with biochemical recurrence of prostate cancer after definitive or salvage local therapy in the absence of metastatic disease represent a group well suited to a novel therapeutic intervention. Imatinib mesylate (Gleevec) is a protein-tyrosine kinase inhibitor that 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 nonmetastatic, androgen-sensitive prostate cancer after local therapy.


METHODS
Twenty-seven patients were treated with imatinib mesylate 400 mg twice daily for up to 12 months. Three patients (11%) completed less than 4 weeks of therapy and were included in the intent-to-treat analysis of the response to therapy.


RESULTS
Of the 27 patients treated, 5 (18.5%) had a stable prostate-specific antigen (PSA) during the course of treatment; 2 patients (7.4%) experienced a partial response. The remaining 20 patients (74.1%) demonstrated PSA progression. The median progression-free survival was 3 months. The proportion of patients achieving a partial PSA response during therapy did not significantly differ from the null rate of 5% (P = 0.394). Seven patients (25.9%) discontinued therapy secondary to grade 1 to 3 toxicities. No irreversible National Institutes of Health Common Toxicity Criteria grade 3 or 4 toxicities occurred. Grade 3 and 4 toxicity included leukopenia (3.7%), serum glutamic-oxaloacetic transaminase (3.7%) and serum glutamic-pyruvic transaminase (3.7%) elevation, and rash (18.5%).


CONCLUSIONS
The results of our study have demonstrated that imatinib mesylate delivered at a dose of 400 mg twice daily is associated with a moderate degree of toxicity and a limited PSA response in this patient population.
Bajaj
Gopal K
GK
Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.
Zhang
Zhe
Z
Garrett-Mayer
Elizabeth
E
Drew
Renee
R
Sinibaldi
Victoria
V
Pili
Roberto
R
Denmeade
Samuel R
SR
Carducci
Michael A
MA
Eisenberger
Mario A
MA
DeWeese
Theodore L
TL
D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D012008:Recurrence; D016879:Salvage Therapy; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D011505:Protein-Tyrosine Kinases; D017430:Prostate-Specific Antigen