title: Phase II study of methotrexate, vinblastine, doxorubicin, and cisplatin in patients with squamous cell carcinoma of the upper respiratory or alimentary passages of the head and neck.
abstract: BACKGROUND
  The chemotherapy drugs methotrexate, vinblastine, doxorubicin, and cisplatin have shown activity in patients with recurrent or metastatic squamous cell carcinoma arising from the upper respiratory or alimentary passages of the head and neck. This study was undertaken to assess the antitumor activity and toxicity profile of the drug combination methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) in this patient population.
  
  
  METHODS
  Patients with histologically confirmed unresectable, recurrent, or metastatic squamous cell carcinoma arising from the upper respiratory or alimentary passages of the head and neck were treated with MVAC over a 4-week cycle. The doses were as follows: 30 mg/m2 of methotrexate on Days 1, 15, and 22; 3 mg/m2 of vinblastine on Days 2, 15, and 22; 30 mg/m2 of doxorubicin on Day 2; and 70 mg/m2 of cisplatin on Day 2. The total cumulative dose of doxorubicin was not to exceed 450 mg/m2. Treatment was discontinued after four cycles for those whose disease remained stable. Patients were evaluated for chemotherapy response, progression free survival, and survival.
  
  
  RESULTS
  Thirty-six patients were accrued onto this study between April 1993 and February 1996. One patient (3%) with a history of cardiac heart failure was declared ineligible. Severe leukopenia (leukocyte count < 2000 cells/m3) was observed in 55% of the patients during the first cycle of treatment and in 81% of the patients during the entire course of their treatment. The overall objective response rate over the first 4 cycles of treatment was 46% (90% confidence interval [CI], 33-60%). Two of the 18 patients who responded had a complete response. The median time to progression was 19 weeks, and 1-year progression free survival rate was 17% (95% CI, 8-36%). The median survival was 49 weeks, and the 1-year survival rate was 43% (95% CI, 29-63%). Among the 22 patients with unresected residual or recurrent disease, the median time to progression was 11 weeks, and 1-year progression free survival rate was 14% (95% CI, 5-39%), and median survival was 24 weeks, and the 1-year survival rate was 36% (95% CI, 21-63%). Among the 13 patients with metastatic disease, the median time to progression was 26 weeks, and the 1-year progression free survival rate was 23% (95% CI, 9-62%), the median survival was 54 weeks, and the 1-year survival rate was 54% (95% CI, 33-89%).
  
  
  CONCLUSIONS
  Methotrexate, vinblastine, doxorubicin, and cisplatin is an active chemotherapy regimen in patients with recurrent or metastatic squamous cell cancer arising from the upper respiratory or alimentary passages of the head and neck.
authors: Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA. okuno.scott@mayo.edu
authors: Scott H
authors: SH
authors: Okuno
authors: James A
authors: JA
authors: Mailliard
authors: Vera J
authors: VJ
authors: Suman
authors: John H
authors: JH
authors: Edmonson
authors: Edward T
authors: ET
authors: Creagan
authors: Suresh
authors: S
authors: Nair
authors: Ralph
authors: R
authors: Levitt
authors: John W
authors: JW
authors: Kugler
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002945:Cisplatin / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D012142:Respiratory Tract Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate; D016896:Treatment Outcome; D014747:Vinblastine / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D014747:Vinblastine; D004317:Doxorubicin; D002945:Cisplatin; D008727:Methotrexate