Erlotinib (E), cisplatin (C) and radiotherapy (RT) for patients with locally advanced squamous cell cervical cancer—A phase I trial

Abstract

5592 Background: Pre-clinical data indicates that inhibition of epidermal growth factor receptor (EGFR) potentiates the effect of RT. This phase I trial aimed to determine the maximal tolerated dose (MTD) of erlotinib, an oral EGFR tyrosine kinase inhibitor, when administered concurrently with standard chemoradiation (CRT) for cervical cancer. Methods: In a modified Fibonacci design, three cohorts of three patients received escalating doses of E (50/100/150 mg) one week before and combined with C (40 mg/m2, weekly, 5 cycles) and RT (external beam RT - 4,500 cGy in 25 fractions, followed by 4 fractions/600 cGy/weekly of brachytherapy). Eligibility criteria included histologically proven squamous cell cervical carcinoma, stage IIB to IIIB; no prior therapy; ECOG PS <3 and adequate end-organ functions. Patients were allowed four additional weeks of toxicity observation after CRT + E before proceeding to the next cohort. Frozen tissue for molecular studies was collected before treatment. Results: Between 12/04 and 8/06, 15 patients were enrolled, 3 at dose level (DL) 50 mg, 4 at DL 100mg and 6 at DL 150 mg. Patients presented median age 47 (36–59), stage IIB (46,2%) and IIIB (53,8%). Overall E+CRT was well tolerated; 3 patients did not complete the planned schedule.One patient at DL 100mg withdrew informed consent due to grade 2 rash; at DL150mg one patient presented Raynaud’s Syndrome and had C interrupted and one patient presented grade 4 hepatotoxicity. The latter was interpreted as DLT and 3 additional patients were included in this cohort. No further grade 4 toxicity occured. Grade 3 toxicity occurred in 33% of the cases, being diarrhea in 3 patients, rash in 2 patients and leukopenia in 1 patient.It shoud be highlighted that E+CRT did not lead to limiting in-field toxicity (radiodermitis, rash or diarrhea). Within the 12 patients who received through E+CRT, median duration of treatment and follow-up was 70 (67–80) days and 9.5 (3–23) months, respectively. The phase II of this trial is ongoing. Conclusions: The MTD has been defined as 150 mg. This is the first report of a combination of erlotinib, cisplatin and pelvic RT. The addition of E to standard CRT does not appear to increase in-field or systemic toxicities. No significant financial relationships to disclose.