title: Promising long-term results with attenuated adverse effects by methotrexate-containing sequential chemoradiation therapy in locally advanced head and neck squamous cell carcinoma.
abstract: OBJECTIVE
  To reduce severe acute and late toxicities without compromising organ preservation survival in patients with locoregionally advanced head and neck squamous cell carcinoma, we performed three-drug induction methotrexate-cisplatin-fluorouracil with weekly cisplatin-fluorouracil concurrent chemoradiation.
  
  
  METHODS
  Two induction courses of methotrexate (40 mg/m(2)/day, days 1, 8 and 15), cisplatin and 5-fluorouracil (25 and 750 mg/m(2)/day, days 1-4) were given in new diagnoses of patients with non-nasopharyngeal locoregionally advanced head and neck squamous cell carcinoma. Responders received concurrent chemoradiation with weekly cisplatin (20 mg/m(2)/day) and 5-fluorouracil (400 mg/m(2)/day) on day 1.
  
  
  RESULTS
  Among 57 patients (58% with Stage IV and hypopharyngeal cancer), the rates of Grade 3-4 toxicity were 30 and 74% during induction and CCRT, respectively. A total of 49 patients completed induction and began concurrent chemoradiation; 47 (96%) completed all planned treatment. With a median follow-up of 62 months (range 19-83 months) for the current survivors, the 3-year overall and disease-specific survival estimates were 50 and 58%, respectively. The 3-year organ preservation survival was 74% in patients who achieved complete remission after concurrent chemoradiation, and 96% of current survivors are tracheotomy and feeding tube-free. No patient without local/regional failure suffered from distant metastasis.
  
  
  CONCLUSIONS
  Methotrexate-cisplatin-fluorouracil induction chemotherapy followed by weekly cisplatin-fluorouracil concurrent chemoradiation is an acute and late toxicity-acceptable protocol without attenuating organ preservation survival in patients with locoregionally advanced head and neck squamous cell carcinoma. In this patient cohort with advanced head and neck squamous cell carcinoma, overall and organ preservation survivals were encouraging, and provided promising long-term benefits of this approach.
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Taipei Veterans General Hospital and National Yang Ming University, No. 201, Sec. 2, Shih-Pai Road, Taipei 112, Taiwan. tltsai@vghtpe.gov.tw
authors.forename: Tung-Lung
authors.initials: TL
authors.lastname: Tsai
authors.forename: Pen-Yuan
authors.initials: PY
authors.lastname: Chu
authors.forename: Shyh-Kuan
authors.initials: SK
authors.lastname: Tai
authors.forename: Yi-Fen
authors.initials: YF
authors.lastname: Wang
authors.forename: Muh-Hwa
authors.initials: MH
authors.lastname: Yang
authors.forename: Ling-Wei
authors.initials: LW
authors.lastname: Wang
authors.forename: Jiing-Feng
authors.initials: JF
authors.lastname: Lirng
authors.forename: Shyue-Yih
authors.initials: SY
authors.lastname: Chang
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000532:radiotherapy*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D011788:Quality of Life; D011878:Radiotherapy / Q000009:adverse effects; D012074:Remission Induction; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: D002945:Cisplatin; D005472:Fluorouracil; D008727:Methotrexate