Phase II trial of cisplatin, tegafur plus uracil and leucovorin as neoadjuvant chemotherapy in patients with squamous cell carcinoma of the oropharynx and hypopharynx.

We evaluated the efficacy and toxicity of cisplatin, tegafur plus uracil and leucovorin as neoadjuvant chemotherapy for locally advanced squamous cell carcinoma (SCC) of the oropharynx and hypopharynx. Forty-six patients (stage IV, 83%; N2/3, 52%) were treated with PUL (50 mg/m2 cisplatin on day 1, 300 mg/m2 tegafur plus uracil orally and 60 mg leucovorin orally on days 1-14) over a 14-day cycle. Evaluation after 3 cycles led to chemotherapy termination if primary tumor responses were less than partial responses. Otherwise, PUL was continued up to 6 cycles before locoregional therapy. Patients achieving at least good partial responses at the primary site after neoadjuvant chemotherapy received radiotherapy for organ preservation. Chemotherapy responses were analyzed by intent-to-treat. Response rates of primary sites were 71.7% (33 of 46) with 34.8% (16 of 46) showing a complete response. Thirty patients (65.2%) achieved good partial responses at the primary site. Overall response and complete response rates of neck lymph nodes were 68.6% (24 of 35) and 25.7% (nine of 35). The combined response rate of primary site and neck lymph nodes was 63% (95% confidence interval 48.5-77.5%) with a complete response rate of 15.2%. Toxicities of WHO grade 3-4 included anemia (19.6%), diarrhea (17.4%) and neutropenia (8.7%). With a median follow-up of 36 months, overall survival and disease-free survival rates were 45.7% (21 of 46) and 41.3% (19 of 46); organ preservation rate was 90% (19 of 21). We concluded that the outpatient PUL regimen was a moderately effective, less-toxic neoadjuvant chemotherapy for SCC of the oropharynx and hypopharynx. PUL should be studied further with other active agents or radiotherapy.