A phase I/II trial of gefitinib given concurrently with radiotherapy in patients with nonmetastatic prostate cancer.
e16079 Background: We estimated the safety and tolerability of 250 mg gefitinib q.d. given concurrently with three- dimensional conformal radiotherapy (3D-CRT) in patients with non-metastatic prostate cancer (PC).


METHODS
42 patients with T2/T3N0M0 PC were treated in a single centre, non-randomized study (study code ZD1839/IL0118). PSA<20 and good performance status (WHO 0-1) were required. Adjuvant or neo-adjuvant hormonal treatments were not allowed. 250 mg gefitinib q.d. was started one week before and lasted for the duration of radiation therapy. 50.4 Gy (1.8 Gy/day) of 3D-CRT was administered to the tumor, prostate and seminal vesicles, followed by a 22 Gy booster (2 Gy/day) for a 72.4 Gy total dose. EGFR expression, presence of EGFRvIII and activated pEGFR were studied. Levels of serum TNF, IL-1 α and IL-6 were also evaluated.


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 and 12 (28.6%) prematurely discontinued because of adverse events. Dose-limiting toxicities were recorded in 16 (38.1%) patients, the most common of which was grade 3-4 transaminase increase (6 patients). After median follow-up of 38 months nobody had died of PC. The estimated PSA-free survival rate at 4 years (Kaplan-Meier) was 97%, hormone-free survival 91% and overall survival 87%. These figures compared favourably with matched, non-randomized patients treated with radiation only. Data on biochemical analyses will be presented.


CONCLUSIONS
The combination of gefitinib and radiation is reasonably well tolerated and has promising activity in non-metastatic PC. A randomized study is being discussed for evaluating the efficacy of the approach. [Table: see text].