title: Phase II trial of cisplatin, tegafur plus uracil and leucovorin as neoadjuvant chemotherapy in patients with squamous cell carcinoma of the oropharynx and hypopharynx.
abstract: 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.
authors.affiliation: Division of Hematology/Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan. whm526@ms12.hinet.net
authors.forename: Hung-Ming
authors.initials: HM
authors.lastname: Wang
authors.forename: Chung-Tsen
authors.initials: CT
authors.lastname: Hsueh
authors.forename: Cheng-Su
authors.initials: CS
authors.lastname: Wang
authors.forename: I-How
authors.initials: IH
authors.lastname: Chen
authors.forename: Chun-Ta
authors.initials: CT
authors.lastname: Liao
authors.forename: Ming-Hsui
authors.initials: MH
authors.lastname: Tsai
authors.forename: Shih-Peng
authors.initials: SP
authors.lastname: Yeh
authors.forename: Joseph Tung-Chieh
authors.initials: JT
authors.lastname: Chang
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D009959:Oropharyngeal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate; D005641:Tegafur / Q000008:administration & dosage; D014498:Uracil / Q000008:administration & dosage
chemical_list: D005641:Tegafur; D014498:Uracil; D002945:Cisplatin; D002955:Leucovorin