Purpose: The cytochrome P-450 (CYP) and glutathione S-transferase (GST) enzyme systems modulate the carcinogenic effects of tobacco. Therefore, the expression of these enzymes may be in part responsible for the observed interindividual and inter-racial differences in the risk of development of squamous cell carcinoma of the head and neck (SCCHN). The first aim of this study was to evaluate the feasibility of measuring the expression of the CYP and GST in target tissue from the head and neck. The second aim was to compare the expression of CYPs 1A1, 2E1, and 3A4 in squamous epithelium from African-American and Caucasian pediatric patients. The third aim was to compare the expression of CYPs 1A1, 2E1, 3A4, and GST-on the p16 expression in patients with SCCHN.Experimental Design: The expression of CYP 1A1, 2E1, 3A4, GST-, and p16 was quantified by immunoblotting. Expression of CYPs 1A1, 2E1, and 3A4 was quantified in tissue from 160 pediatric patients undergoing tonsillectomy. Expression of CYPs 1A1, 2E1, 3A4, GST-, and p16 was determined in 46 resected SCCHN patients.Results: Large interindividual variability in the expression of these enzymes was observed in the pediatric and adult populations. No significant difference was observed in CYP 1A1, 2E1, and 3A4 expression of Caucasian and African-American patients. There was no correlation between p16 and enzyme expression in patients with SCCHN.Conclusion: Evaluation of CYP expression in the target tissue of interest is feasible. The clinical significance of CYPs and GST-alterations in the risk of developing SCCHN will need to be investigated in larger trials.

Background A phase I study and an institutional pilot study in patients with metastatic/recurrent squamous cell carcinoma of the head and neck (SCCHN), utilizing biweekly gemcitabine-paclitaxel showed an overall response rate of 53%. This phase II trial was conducted to determine the feasibility, tolerability and efficacy of this combination. Methods Patients with metastatic/recurrent SCCHN were treated with gemcitabine (3,000 mg/m2) and paclitaxel (150mg/m2) on days 1 and 15 of every 28 day cycle. Results In 57 patients with measurable disease, median progression free survival was 4 months and median overall survival was 8 months. Overall response rate of 28% and disease stabilization in 19% was seen. There were no treatment related deaths with Grade 3/4 hematologic toxicity seen in 20% of the patients. Conclusions Biweekly gemcitabine-paclitaxel is feasible, well tolerated and demonstrated reasonable efficacy. This may be an alternative for patients who are not candidates for platinum-based chemotherapy.