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.
Department of Medical Oncology, Peter MacCallum Cancer Centre, East Melbourne, Australia.
Carmel
C
Pezaro
Mark A
MA
Rosenthal
Howard
H
Gurney
Ian D
ID
Davis
Craig
C
Underhill
Michael J
MJ
Boyer
Dusan
D
Kotasek
Benjamin
B
Solomon
Guy C
GC
Toner
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