Gefitinib combined with endocrine manipulation in patients with hormone-refractory prostate cancer: quality of life and surrogate markers of activity.
We investigated efficacy of gefitinib in hormone-refractory prostate cancer. Between March 2003 and December 2004, 23 patients with hormone-refractory prostate cancer were assigned to receive 250 mg oral gefitinib daily in addition to antiandrogen and luteinizing hormone-releasing hormone analogue for at least 2 months or until disease progression. Patients with progression stopped antiandrogen therapy, and received gefitinib and the luteinizing hormone-releasing hormone analogue. Serum HER2 and epidermal growth factor receptor extracellular domain were evaluated every 2 months. Gefitinib treatment did not result in any objective measurable response or responses in prostate-specific antigen. Median time to progression was 70 days (33-336). Median overall survival was 293 days (25-75 percentile: 235-349). HER2 extracellular domain mean value was 9.6 ng/ml (range 6.9-13.3) at basal time and was 10.1 (range 6.0-14.1) after 2 months. Epidermal growth factor receptor mean basal value was 51.0 ng/ml (range 41.4-75.3). After 2 months of treatment the mean value was 51.1 ng/ml (range 41.5-61.4). One patient had reduction in the pain score from baseline without an increase in the analgesic score. Four patients (17%) out of 23 had pain progression with an increase from baseline of at least 25% in the analgesic score. The study was discontinued before target accrual was reached owing to lack of efficacy of the drug. Our results do not support the efficacy of gefitinib in combination with endocrine treatment for hormone-refractory prostate cancer.
Division of Medical Oncology, Clinical Pharmacology and New Drugs Development Unit, European Institute of Oncology, Milan, Italy. Giuseppe.curigliano@ieo.it
Giuseppe
G
Curigliano
Filippo
F
De Braud
Maria
M
Teresa Sandri
Giuseppe
G
Renne
Laura
L
Zorzino
Epifanio
E
Scardino
Bernardo
B
Rocco
Gianluca
G
Spitaleri
Tommaso
T
De Pas
Cristina
C
Noberasco
Franco
F
Nolè
Fabrizio
F
Verweij
Victor
V
Matei
Ottavio
O
De Cobelli
D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D023381:Endpoint Determination; D000077156:Gefitinib; D018773:Genes, erbB-1 / Q000235:genetics; D018734:Genes, erbB-2 / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000523:psychology*; D011788:Quality of Life; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D011795:Surveys and Questionnaires
D000726:Androgen Antagonists; D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D011799:Quinazolines; D000077156:Gefitinib