phase II study of gemcitabine concurrent with radiation in locally advanced squamous cell carcinoma of head and neck: a trial of the cancer research group Pakistan

ABSTRACT

To evaluate the efficacy and toxicity of weekly gemcitabine as a radiosensitizer concurrent with radical radiotherapy in locally advanced carcinoma of head and neck. From August 2001 to January 2002, thirty-nine patients with stage III or IV B inoperable carcinoma of head and neck were enrolled. Patients with histopathologically confirmed squamous cell carcinoma with at least one bidimensionally measurable lesion, no prior chemotherapy or radiotherapy, and a KPS of 60 or above were included. Patients with nasopharyngeal, glottic or sub-glottic cancer were excluded. Gemcitabine 150mg/m2 or a total dose not exceeding 200 mg was given on day 1, 8, 15, 22, 29, and 36 during radiation treatment. Radiation was delivered with conventional fractionation to a total dose of 66-70Gy. Miller's criteria was used for response evaluation. RTOG/EORTC acute radiation [and chemotherapy] morbidity scoring system and WHO grading of acute and sub acute toxicity criteria were used for documentation of toxicity. All 39 patients were evaluable for toxicity but only 35 patients were evaluable for response. An overall response rate of 94.3% [95% CI; 80.8-99.3] was seen with a partial response rate of 71.4% and complete response rate of 22.9% [95%CI; 10.4-40.1]. Grade 3 mucositis was seen in 28 patients [71.8%]. Grade 4 mucositis was seen in 2 patients [5.1%]. Pharyngeal toxicity was the second-most common toxicity. Grade 2 toxicity was seen in 12 patients [30.8%] and grade 3 in 6 patients [15.4%]. Despite vigorous symptomatic and supportive care acute toxicities led to treatment interruption in 40% of patients. A high overall response rate and a high rate of acute toxicity are seen at a weekly gemcitabine dose of 150mg/m2 concurrent with radiation. This shows that gemcitabine is a potent radiosensitizer with a marked tumor and normal tissue radio sensitization