Weekly Gemcitabine and Cisplatin in Combination With Radiotherapy in Patients With Locally Advanced Head-and-Neck Cancer: Phase I Study

Journal Article · Tue Nov 15 04:00:00 EST 2011 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/J.IJROBP.2011.02.012· OSTI ID:22054367

Afonso, Sergio Luis ^[1]; Cardoso Tavares, Vivian ^[2]; Stefano, Eduardo Jose ^[3]

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1. Clinical Oncology Department, Faculty of Medicine of Marilia, Sao Paulo (Brazil)
2. Head and Neck Oncology Department, Faculty of Medicine of Marilia, Sao Paulo (Brazil)
3. Radiation Oncology Department, Faculty of Medicine of Marilia, Sao Paulo (Brazil)

Purpose: To 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 Materials: Patients 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{sup 2} and that of gemcitabine was 10 mg/m{sup 2} in 3 patients, with a subsequent dose escalation of 10 mg/m{sup 2} of cisplatin only for 3 new patients. In the next levels, only a dose escalation of gemcitabine with 10 mg/m{sup 2} for each new cohort was used (Level 1, 10 mg/m{sup 2} of gemcitabine and 20 mg/m{sup 2} of cisplatin; Level 2, 10 mg/m{sup 2} of gemcitabine and 30 mg/m{sup 2} of cisplatin; and Level 3, 20 mg/m{sup 2} of gemcitabine and 30 mg/m{sup 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. Results: From 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. Conclusion: Gemcitabine 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{sup 2} of gemcitabine and 30 mg/m{sup 2} of cisplatin with an acceptable tolerability profile.

• OSTI ID: 22054367
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Journal Name: International Journal of Radiation Oncology, Biology and Physics Journal Issue: 4 Vol. 81; ISSN IOBPD3; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
CHEMOTHERAPY
DERMATITIS
DOSES
HEAD
IRRADIATION
NECK
NEOPLASMS
PATIENTS
RADIOTHERAPY
TOXICITY