A phase II trial of imatinib mesylate in patients with biochemical relapse of prostate cancer after definitive local therapy.
OBJECTIVE
To determine the biological effects of imatinib mesylate (STI-571, Gleevec; Novartis Pharmaceuticals, Inc., East Hanover, NJ, USA), as measured by prostate-specific antigen (PSA) kinetics in men with biochemical relapse of prostate cancer after definitive local therapy.


METHODS
Men with prostate cancer, who had had definitive local therapy, with nonmetastatic recurrent disease as manifested by a rising PSA level, were enrolled on this phase II trial. Men received 400 mg of imatinib mesylate orally twice daily and continuously until disease progression or unacceptable toxicity. The PSA level was measured monthly.


RESULTS
In all, 20 men with biochemically relapsed prostate cancer were treated. The median pretreatment PSA level was 5.4 ng/mL. Of the 19 evaluable men, one achieved a >or= 50% reduction in PSA level and two had decreases of <50%. For the 16 men in whom the on-treatment PSA doubling time (PSADT) could be calculated (those with increasing PSA level) the median PSADT did not increase significantly (5.8 vs 7.2 months, P = 0.64). Eleven of 20 men discontinued therapy due to toxicity and the trial was stopped early due to toxicity.


CONCLUSIONS
Based on the lack of PSA modulation and pronounced toxicities leading to early closure of this trial, further study of single-agent imatinib mesylate at this dose (400 mg twice daily) cannot be recommended in this patient population.
Lin
Amy M
AM
University of California/San Francisco, San Francisco, CA 94115, USA.
Rini
Brian I
BI
Weinberg
Vivian
V
Fong
Kristen
K
Ryan
Charles J
CJ
Rosenberg
Jonathan E
JE
Fong
Lawrence
L
Small
Eric J
EJ
D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001549:Benzamides; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000188:drug therapy*; D010879:Piperazines / Q000009:adverse effects*; D017430:Prostate-Specific Antigen / Q000097:blood / Q000187:drug effects*; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy*; D011743:Pyrimidines / Q000009:adverse effects*; D017211:Treatment Failure
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D017430:Prostate-Specific Antigen