A phase I/II trial of gefitinib given concurrently with radiotherapy in patients with nonmetastatic prostate cancer.
OBJECTIVE
To estimate the safety and tolerability of daily administration of 250 mg of gefitinib given concurrently with three-dimensional conformal radiotherapy for patients with nonmetastatic prostate cancer.


METHODS
A total of 42 patients with T2-T3N0M0 tumors were treated in a nonrandomized single-center study. A prostate-specific antigen (PSA) level of <20 and a good performance status (WHO, 0-1) were required. Adjuvant or neoadjuvant hormone treatments were not allowed. A daily regimen of 250 mg of gefitinib was started 1 week before radiation therapy began and lasted for the duration of radiation therapy. A dose of 50.4 Gy (1.8 Gy/day) was administered to the tumor, prostate, and seminal vesicles, followed by a 22-Gy booster (2 Gy/day) for a total dose of 72.4 Gy. Correlative studies included analysis of epidermal growth factor receptor (EGFR), EGFRvIII, and phosphorylated EGFR in tumors and tumor necrosis factor, interleukin-1alpha (IL-1alpha), and IL-6 in serum.


RESULTS
Maximum tolerated dose was not reached in phase I (12 patients), and 30 additional patients were treated in phase II. Thirty (71.4%) patients completed trial medication. Dose-limiting toxicities were recorded for 16 (38.1%) patients, the most common of which was a grade 3 to 4 increase in transaminase (6 patients). After a median follow-up of 38 months, there were no deaths due to prostate cancer. The estimated PSA relapse-free survival rate at 4 years (Kaplan-Meier) was 97%, the salvage therapy-free survival rate was 91%, and the overall survival rate was 87%. These figures compared favorably with those of matched patients treated with radiation only at higher doses.


CONCLUSIONS
The combination of gefitinib and radiation is reasonably well tolerated and has promising activity against nonmetastatic prostate cancer.
Joensuu
Greetta
G
Transplantation Laboratory and Haartman Institute and Finnish Institute for Molecular Medicine, University of Helsinki, Helsinki, Finland.
Joensuu
Timo
T
Nokisalmi
Petri
P
Reddy
Chandana
C
Isola
Jorma
J
Ruutu
Mirja
M
Kouri
Mauri
M
Kupelian
Patrick A
PA
Collan
Juhani
J
Pesonen
Sari
S
Hemminki
Akseli
A
D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D003131:Combined Modality Therapy / Q000009:adverse effects / Q000379:methods; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D066246:ErbB Receptors / Q000032:analysis; D000077156:Gefitinib; D006801:Humans; D053582:Interleukin-1alpha / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D009367:Neoplasm Staging; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects*; D011879:Radiotherapy Dosage; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000970:Antineoplastic Agents; D053582:Interleukin-1alpha; D015850:Interleukin-6; D009363:Neoplasm Proteins; D011799:Quinazolines; D014409:Tumor Necrosis Factor-alpha; C410723:epidermal growth factor receptor VIII; D066246:ErbB Receptors; D017430:Prostate-Specific Antigen; D000077156:Gefitinib