• Gustavo Arruda Viani, Sergio Luis Afonso, Vivian Cardoso Tavares, Lucas Godoi Bernardes da Silva, and Eduardo Jose Stefano.
• Radiation Oncology Department, Faculty of Medicine of Marilia, São Paulo, Brazil. gusviani@gmail.com
• Int. J. Radiat. Oncol. Biol. Phys. 2011 Nov 15; 81 (4): e231-5.

PurposeTo define the maximum tolerated dose by describing the dose-limiting toxicity (DLT) of weekly gemcitabine and cisplatin in patients with locally advanced head-and-neck (LAHN) cancer concomitant to irradiation.Methods And MaterialsPatients with LAHN cancer were enrolled in a prospective, dose-escalation Phase I study. Toxicity was graded according to the Common Toxicity Criteria score. Maximum tolerated dose was defined when DLT developed in 2 of 6 patients. The starting dose of cisplatin was 20 mg/m(2) and that of gemcitabine was 10 mg/m(2) in 3 patients, with a subsequent dose escalation of 10 mg/m(2) of cisplatin only for 3 new patients. In the next levels, only a dose escalation of gemcitabine with 10 mg/m(2) for each new cohort was used (Level 1, 10 mg/m(2) of gemcitabine and 20 mg/m(2) of cisplatin; Level 2, 10 mg/m(2) of gemcitabine and 30 mg/m(2) of cisplatin; and Level 3, 20 mg/m(2) of gemcitabine and 30 mg/m(2) of cisplatin). Radiation therapy was administered by use of a conformal technique over a period of 6 to 7 weeks in 2.0-Gy daily fractions for 5 consecutive days per week to a total dose of 70 Gy.ResultsFrom 2008 to 2009, 12 patients completing 3 dose levels were included in the study. At Dose Level 3, 1 of 3 patients had DLT with Grade 3 mucositis. Of the next 3 required patients, 2 showed DLT with Grade 3 dermatitis. At a follow-up of 3 months, 10 of 12 evaluable patients (83.3%) obtained a complete response and 1 patient (8.3%) obtained a partial response. Among the complete responders, at a median follow-up of 10 months (range, 6-14 months), 9 patients are alive and disease free.ConclusionGemcitabine at low doses combined with cisplatin is a potent radiosensitizer effective in patients with LAHN cancer. The recommended Phase II dose is 10 mg/m(2) of gemcitabine and 30 mg/m(2) of cisplatin with an acceptable tolerability profile.Copyright © 2011 Elsevier Inc. All rights reserved.

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