An open-label, single-arm phase two trial of gefitinib in patients with advanced or metastatic castration-resistant prostate cancer.
OBJECTIVE
To determine whether the oral epidermal growth factor receptor (EGFR) inhibitor gefitinib (ZD1839, Iressa has clinical efficacy in patients with castration-resistant prostate cancer (CRPC).


METHODS
Multicenter open-label phase 2 study. Fifty-one male patients with CRPC and rising PSA levels were enrolled to obtain the target enrollment of 38 patients who completed at least 3 months of treatment with continuous gefitinib 500 mg/d. The primary end point was the prostate-specific antigen (PSA) response rate, as defined by a confirmed 50% decline in serum PSA.


RESULTS
One patient had a confirmed PSA response, giving a response rate of 2.0% (95% CI 0.1-10.4%). The median time to progression was 28 days and the median time on study was 85 days. The majority of patients had a stable performance status while on study. Of the 51 patients who received at least 1 dose of gefitinib, 13 patients had a dose reduction and 9 patients withdrew because of an adverse event.


CONCLUSIONS
There was minimal evidence of single-agent gefitinib activity in CRPC. The treatment was associated with clinically relevant toxicities, which responded to dose interruption or reduction.
Pezaro
Carmel
C
Department of Medical Oncology, Peter MacCallum Cancer Centre, East Melbourne, Australia.
Rosenthal
Mark A
MA
Gurney
Howard
H
Davis
Ian D
ID
Underhill
Craig
C
Boyer
Michael J
MJ
Kotasek
Dusan
D
Solomon
Benjamin
B
Toner
Guy C
GC
D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000009:adverse effects; D014408:Biomarkers, Tumor / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D066246:ErbB Receptors / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D000077156:Gefitinib; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009919:Orchiectomy; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000401:mortality; D011799:Quinazolines / Q000008:administration & dosage* / Q000009:adverse effects; D018570:Risk Assessment; D016037:Single-Blind Method; D016019:Survival Analysis; D013739:Testosterone / Q000097:blood*; D016896:Treatment Outcome
D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D011799:Quinazolines; D013739:Testosterone; D066246:ErbB Receptors; D017430:Prostate-Specific Antigen; D000077156:Gefitinib