A phase II trial of imatinib mesylate in patients with prostate specific antigen progression after local therapy for prostate cancer.
OBJECTIVE
To test the hypothesis that progression of androgen sensitive prostate cancer is dependent on growth factors, such as platelet derived growth factor (PDGF), and inhibition of PDGF receptor (PDGF-R) with imatinib will induce anti-tumor activity.


METHODS
This phase II study evaluated imatinib in patients with androgen sensitive prostate cancer and prostate specific antigen (PSA) progression after local therapy. Patients received 400 mg of imatinib orally twice a day for 24 weeks (six cycles). Patients were monitored every 4 weeks for an effect on PSA and toxicity. Immunohistochemistry (IHC) for PDGF-R was performed in available tumor specimens.


RESULTS
Twenty-one patients were enrolled on this trial with a median age of 64 years. A total of 72 cycles of therapy were administered. Sixteen patients were evaluable for a response. Nine of the 16 patients demonstrated a stable PSA. Seven patients demonstrated PSA progression. Grade 3 and 4 toxicity included rash (4.1%), hematuria (1.4%), diarrhea (1.4%), and neutropenia (2.7%). Testosterone levels did not change during therapy. Four patients with available tumor demonstrated PDGF-R alpha and beta by IHC.


CONCLUSIONS
This first study evaluated the efficacy and safety of imatinib in patients with early androgen sensitive prostate cancer following local therapy. As a single agent at this dosing, imatinib had limited biochemical activity.
Rao
Kamakshi
K
The Dean and Betty Gallo Prostate Cancer Center at The Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08901, USA.
Goodin
Susan
S
Levitt
Michael J
MJ
Dave
Nisha
N
Shih
Weichung J
WJ
Lin
Yong
Y
Capanna
Terry
T
Doyle-Lindrud
Susan
S
Juvidian
Parisa
P
DiPaola
Robert S
RS
D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001549:Benzamides; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects; D017430:Prostate-Specific Antigen / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D017211:Treatment Failure
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D017479:Receptors, Platelet-Derived Growth Factor; D017430:Prostate-Specific Antigen