Erlotinib (E) combined with cisplatin (C) and radiotherapy (RT) for patients with locally advanced squamous cell cervical cancer: A phase II trial

Abstract

5511 Background: New strategies beyond standard chemoradiation (CRT) are needed in locally advanced squamous cell cervical carcinoma. Combinations that increase the complete response rates (CR) may lead to longer progression-free and overall survival in cervical cancer. Pre-clinical data indicates that inhibition of epidermal growth factor receptor (EGFR) enhances the effect of C and RT. We previously reported the results of the phase I of E when administered concurrently with standard CRT for locally advanced cervical cancer that defined the safety and the maximal tolerated dose of 150mg/day for the combination. Methods: 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 (pts) received E 150mg/day one week before and combined with C (40mg/m2, weekly, 5 cycles) and RT (external beam RT - 4500cGy in 25 fractions, followed by 4 fractions/600cGy/weekly of brachytherapy). Results: Between 02/2006 and 10/2007, 37 pts were enrolled. Two pts did not complete the planned schedule (one presented Raynaud’s Syndrome and had C interrupted and one presented grade 4 hepatotoxicity). Twelve pts are still under treatment, 25 pts are available for toxicity and 23 for response evaluation. Within the 23 pts who received through E+CRT, median duration of treatment was 77(64–106) days. Pts presented median age 43(28–68), stage IIB 11(47.8%), IIIA 1(4.3%) and IIIB 11(47.8%). Overall E+CRT was well tolerated. Significant grade 3 toxicities were diarrhea and skin rash in 3(12%) and 5 (20%) pts, respectively. Twenty-one pts (91.3%; IC 95% 70.5 - 98.5) presented CR and 2 (8.7%) presented partial response. With a median follow-up of 9(3–25) months, none of the 23 pts progressed. Conclusions: Our data indicate that the combination of E+CRT is feasible and leads to high CR (91.3%) compared to historical CRT data (38–75%). To our knowledge this is the first report of E+CRT in cervical cancer pts. The trial has finished accrual and final results will be presented at the meeting. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Roche