title: Phase II and biologic study of interferon alfa, retinoic acid, and cisplatin in advanced squamous skin cancer.
abstract: OBJECTIVE
  The purpose of this study was to test interferon alfa (IFNalpha), 13-cis-retinoic acid (13cRA), and cisplatin biochemotherapy in advanced squamous cell carcinoma (SCC) of the skin.
  
  
  METHODS
  Patients with advanced skin SCC received IFNalpha (5 x 10(6) IU/m(2), subcutaneous injection, three times a week), 13cRA (1 mg/kg, orally, daily), and cisplatin (20 mg/m(2), intravenous injection, weekly) in a phase II trial. The growth inhibition, cell-cycle, and apoptosis activity of these agents was evaluated in two skin SCC cell lines (SRB1-m7 and SRB12-p9).
  
  
  RESULTS
  Thirty-nine patients were enrolled. All were assessable for survival, 35 for response and toxicity (median follow-up was 38 months). The overall and complete response rates were 34% and 17%, respectively, with median durations of 9 and 35.4 months, respectively. The response rate was higher in locally advanced (67%) than metastatic (17%) disease (P =.007). Median survival was 14.6 months. One-, 2-, and 5-year survival rate estimates were 58%, 32%, and 21%, respectively. Toxicity included generally mild to moderate fatigue and mucocutaneous dryness, moderate to severe neutropenia (38%), and neutropenic fever (6%). There were no treatment-related deaths. In vitro growth inhibition and apoptosis effects of cisplatin were differential and inversely associated with those of retinoic acid and especially IFNalpha in two skin SCC lines.
  
  
  CONCLUSIONS
  The rising incidence, morbidity, and mortality of advanced skin SCC are a major challenge for clinical oncologists. Combined 13cRA, IFNalpha, and cisplatin was clinically active in extensive locally advanced disease. Each agent had independent, non-cross-resistant biologic effects in vitro, which may account for the combination's clinical activity.
authors.affiliation: Department of Thoracic/Head and Neck Medical Oncology, Diagnostic Imaging, Biostatistics, Head and Neck Surgery, and Clinical Cancer Prevention, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030-4095, USA.
authors.forename: Dong M
authors.initials: DM
authors.lastname: Shin
authors.forename: Bonnie S
authors.initials: BS
authors.lastname: Glisson
authors.forename: Fadlo R
authors.initials: FR
authors.lastname: Khuri
authors.forename: John L
authors.initials: JL
authors.lastname: Clifford
authors.forename: Gary
authors.initials: G
authors.lastname: Clayman
authors.forename: Steven E
authors.initials: SE
authors.lastname: Benner
authors.forename: Arlene A
authors.initials: AA
authors.lastname: Forastiere
authors.forename: Lawrence
authors.initials: L
authors.lastname: Ginsberg
authors.forename: Diane
authors.initials: D
authors.lastname: Liu
authors.forename: J Jack
authors.initials: JJ
authors.lastname: Lee
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Myers
authors.forename: Helmuth
authors.initials: H
authors.lastname: Goepfert
authors.forename: Reuben
authors.initials: R
authors.lastname: Lotan
authors.forename: Waun Ki
authors.initials: WK
authors.lastname: Hong
authors.forename: Scott M
authors.initials: SM
authors.lastname: Lippman
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005334:Fever / Q000139:chemically induced; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D016898:Interferon-alpha / Q000008:administration & dosage; D015474:Isotretinoin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016019:Survival Analysis; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured
chemical_list: D016898:Interferon-alpha; D015474:Isotretinoin; D002945:Cisplatin