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Objectives: A subgroup of oropharyngeal squamous cell carcinoma (OPC) is infected with high-risk human papillomavirus (HPV). The object of this study is to evaluate the efficacy of adjuvant chemotherapy with S-1, an oral 5-fluorouracil prodrug, on survival of patients with OPC according to HPV status. Methods: Among OPC patients of stage III or IV who received definitive treatment from 1998 to 2008, 38 who were confirmed tumor-free after primary treatment were analyzed. Before 2003, none of the patients received S-1 adjuvant chemotherapy (S-1(-)-group); however, all patients who were eligible were administered S-1 (S-1(+)-group) after 2003. The expression of thymidylate synthase (TYMS) involved in 5-FU metabolism was also examined in protein and mRNA levels. Results: Although there was a trend to disease-free and overall survival benefit in HPV-negative patients with S-1, it did not achieve statistical significance ( P = .082 and P = .065, respectively). For the HPV-positive patients, the survivals were similar with or without S-1 administration. TYMS-expression in HPV-positive OPC tissues was significantly higher than in HPV-negative ones in both protein and mRNA levels ( P = .0489 and P = .0446, respectively). Conclusion: The current study provides a rationale to plan a randomized trial to compare the efficacy of S-1 according to the HPV status in OPCs.

Objective: Nasopharyngeal cancer (NPC) is radiosensitive and chemosensitive. We evaluated the efficacy of alternating chemoradiotherapy in patients with advanced NPC. Methods: Alternating chemoradiotherapy was initiated in 30 patients with NPC, and 27 patients with cancer stages II (n = 6), III (n = 8), IVA (n = 9), and IVB (n = 4) were retrospectively analyzed. Chemotherapy was initially administered followed by radiotherapy, and chemotherapy, radiotherapy, and chemotherapy were alternately administered. Of the 27 patients, 22 patients received cisplatin (50 mg/m2/day, days 6 and 7) and 5-fluorouracil (5-FU; 800 mg/m2/day, days 1-5), whereas 5 patients received carboplatin (AUC 4-5, day 6) and 5-FU. Results: Of the 27 patients, 19 (70%) received 3 chemotherapy courses. The total duration of alternating chemoradiotherapy was 81 to 101 days (median, 90 days). At a median follow-up of 53 months, the 5-year progression-free survival (PFS) was 71%. Multivariate analysis showed that weight loss and the number of chemotherapy courses had a significant effect on PFS. Conclusion: Alternating chemoradiotherapy led to similar or higher survival rates compared with concurrent chemoradiotherapy, which was characterized by good compliance and adaptable intensity.

Objectives: An intra-arterial chemoradiotherapy regimen (RADPLAT) provides remarkable local control for head and neck cancer. This study evaluates the efficacy of a reduced RADPLAT protocol in patients who are candidates for total laryngectomy. Methods: Forty-three patients with advanced laryngeal cancer were treated with 2 courses of intra-arterial cisplatin infusion (100 mg per body) during 40-Gy irradiation. The patients who showed a greatly diminished tumor received sequential irradiation. The patients with obvious residual disease received chemotherapy during the sequential irradiation. Poor responders, with less than 50% tumor reduction, underwent total laryngectomy. Results: Forty-two patients completed the protocol. All surviving patients were followed for at least 3 years. Thirty-four patients were alive (80% of the supraglottic cases and 87.5% of the glottic cases). Local control was achieved in 27 patients (67.5% of the 11 glottic cases and 64.0% of the supraglottic cases). The glottic cohort showed better progression-free survival rates than did the supraglottic cohort (68.8% and 45.0%, respectively; p = 0.019). There were 2 cases of grade 3 neutropenia and 3 cases of grade 3 mucositis. No patients required tube feeding. One patient required tracheostomy 3 months after the completion of the treatment protocol. Conclusions: Concurrent chemoradiotherapy with a reduced dose of intra-arterial cisplatin is feasible for patients with advanced glottic cancer.

Objectives: This study was designed to evaluate the efficacy and feasibility of our intra-arterial chemotherapy protocol with a lower amount and frequency of cisplatin delivery than in RADPLAT for the treatment of resectable advanced head and neck cancer. Methods: Fifty-one patients with advanced squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx were included in this prospective study. The patients were treated with 3 courses of cisplatin (100 mg at 1 treatment, intra-arterial) and sodium thiosulfate (28 g at 1 treatment, intravenous) once every 2 weeks during concurrent radiotherapy (66 to 70 Gy, 2 Gy per fraction, daily for 5 days over 7 weeks). Nodal metastases larger than 3 cm in diameter were treated with an additional 50 mg of cisplatin. The patients with less than 50% tumor reduction after 40 Gy and 2 courses of chemotherapy were treated with surgery. Results: The protocol was completed for 49 patients. All living patients had a minimum follow-up period of 2 years. Including the 3 patients with salvage surgery, local disease-free control was achieved in 39 patients (80%). For 36 patients (73.5%), disease-free primary organs were preserved at 2 years after treatment. Locoregional disease-free control for 2 years was obtained for 38 patients (77.6%), in 30 of them without salvage surgery. The patients treated with surgery had an overall survival rate similar to that of the patients with a complete response (80% and 84.6%, respectively). The patients with a partial response had a worse prognosis (40%; p = 0069). Conclusions: This treatment regimen is feasible and effective for advanced resectable head and neck cancer.