A multi-institutional phase ii study of SU101, a platelet-derived growth factor receptor inhibitor, for patients with hormone-refractory prostate cancer.
In a multi-institutional Phase II trial, we evaluated the efficacy of a platelet-derived growth factor receptor (PDGF-r) inhibitor, SU101, in patients with hormonerefractory prostate cancer. The patients received a 4-day i.v. loading dose of SU101 at 400 mg/m(2) for 4 consecutive days, followed by 10 weekly infusions at 400 mg/m(2). The primary study end points were a decline in prostate-specific antigen (PSA) and a decrease in measurable tumor. Secondary end points were time to progression and an effect on pain as measured by the Brief Pain Survey. Expression of PDGF-r was examined in both metastatic and archival primary prostate tumor samples. Forty-four patients were enrolled at four centers. The median age was 72 years, the median PSA was 223 ng/ml, and 21 patients had at least one prior chemotherapy. Thirty-nine patients are evaluable for PSA, and three patients demonstrated a PSA decline >50% from baseline (55-99.9% decrease). The median time to progression was 90 days. Of 19 patients evaluable for measurable disease, 1 patient had a partial response. Nine of 35 evaluable patients had significant improvement in pain. The most frequent adverse events were asthenia (75%), nausea (55%), anorexia (50%), and anemia (41%). PDGF-r expression was detected in 80% of the metastases and 88% of primary prostate cancers. The results of this trial may warrant further clinical studies with other PDGF-r inhibitors.
Ko
Y J
YJ
Beth Israel Deaconess Medical Center, Harvard Medical School Boston, Massachusetts 02215, USA.
Small
E J
EJ
Kabbinavar
F
F
Chachoua
A
A
Taneja
S
S
Reese
D
D
DePaoli
A
A
Hannah
A
A
Balk
S P
SP
Bubley
G J
GJ
D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007150:Immunohistochemistry; D007555:Isoxazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077339:Leflunomide; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D007555:Isoxazoles; D017479:Receptors, Platelet-Derived Growth Factor; D017430:Prostate-Specific Antigen; D000077339:Leflunomide