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Phase I Trial of Erlotinib Combined with Cisplatin and Radiotherapy for Patients with Locally Advanced Cervical Squamous Cell Cancer

Authors' Affiliations: ¹ Divisions of Medical Oncology, Radiation Oncology, Gynecology Oncology, and Clinical Research, Instituto Nacional de Câncer, Rio de Janeiro, Brazil; ² ROCHE Pharmaceutical; and ³ University of Washington, Washington, Seattle

Requests for reprints: Carlos Gil Ferreira, Division of Clinical and Translational Research, Research Coordination, Instituto Nacional de Câncer (INCA), Rua André Cavalcanti, 37, segundo andar, Rio de Janeiro-RJ Brazil, 20231-050. E-mail: cferreira{at}inca.gov.br.

Purpose: This phase I trial was aimed to determine the maximum tolerated dose and related toxicity of erlotinib (E) when administered concurrently with standard chemoradiation (CRT) for cervical cancer.

Experimental Design: In a modified Fibonacci design, the study aimed to study three cohorts of at least three patients receiving escalating doses of erlotinib (50/100/150 mg) combined with cisplatin (40 mg/m², weekly, 5 cycles) and radiotherapy (external beam 4,500 cGy in 25 fractions, followed by 4 fractions/600 cGy/weekly of brachytherapy) in squamous cell cervical carcinoma patients, stage IIB to IIIB.

Results: Fifteen patients were enrolled, 3 at dose level (DL) 50 mg, 4 at DL 100 mg, and 8 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. Three patients did not complete the planned schedule. One patient at DL 100 mg withdrew informed consent due to grade 2 rash; at DL 150 mg, 1 patient presented Raynaud's Syndrome and had C interrupted, and another patient presented grade 4 hepatotoxicity. The latter was interpreted as dose limiting toxicity and a new cohort of 150 mg was started. No further grade 4 toxicity occurred. Grade 3 toxicity occurred in 6 cases: diarrhea in 3 patients, rash in 2 patients, and leukopenia in 1 patient. E+CRT did not lead to limiting in-field toxicity.

Conclusions: E+CRT is feasible to locally advanced squamous cell cervical cancer and is well tolerated. The maximum tolerated dose has been defined as 150 mg. To the best of our knowledge, this is the first report of a combination of erlotinib, cisplatin, and pelvic radiotherapy.