title: 13-cis-retinoic acid and interferon alpha-2a: effective combination therapy for advanced squamous cell carcinoma of the skin.
abstract: BACKGROUND
  Retinoids (vitamin A derivatives) and interferon-alpha (IFN-alpha) are potent regulators of malignant cell differentiation and proliferation, and both have immunomodulatory and antiangiogenesis activity. A large body of preclinical and clinical data supports the use of combination therapy with 13-cis-retinoic acid (13-cRA) and IFN-alpha in patients with squamous cell carcinoma of the skin. This carcinoma is an extremely common and frequently severely disfiguring cancer, for which about 10% of patients remain uncured following standard local therapy.
  
  
  OBJECTIVE
  Our purpose was to test whether a 20% or greater complete response rate could be achieved using a combination of these two agents in patients with advanced squamous cell carcinoma of the skin in whom local therapy had failed or was unfeasible or who had regional and/or distant metastases.
  
  
  METHODS
  Thirty-two patients with heavily pretreated, advanced inoperable cutaneous squamous cell carcinoma of the skin were given a combination of oral 13-cRA (1 mg/kg per day) and subcutaneous recombinant human IFN alpha-2a (3 million units per day) for at least 2 months, unless disease progressed earlier, in a phase II trial.
  
  
  RESULTS
  Nineteen (68%) of the 28 assessable patients responded, seven (25%) of whom had complete responses. Response rates were 93% (13 of 14) in patients with advanced local disease (six complete responses), 67% (four of six) in patients with regional disease (no complete responses), and 25% (two of eight) in patients with distant metastases (one complete response). The relationship between decreased response rate and increased extent of disease was highly statistically significant (P less than .005, chi-square test). The median response duration was greater than 5 months. No life-threatening toxic effects occurred in assessable patients treated with this combination, although dose reductions were required in 18 patients. The major limiting side effect in this elderly patient population (median age, 67 years) was cumulative fatigue.
  
  
  CONCLUSIONS
  These results indicate that combined systemic therapy with 13-cRA and IFN alpha-2a is highly effective in patients with advanced squamous cell carcinoma of the skin.
authors.affiliation: Department of Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
authors.forename: S M
authors.initials: SM
authors.lastname: Lippman
authors.forename: D R
authors.initials: DR
authors.lastname: Parkinson
authors.forename: L M
authors.initials: LM
authors.lastname: Itri
authors.forename: R S
authors.initials: RS
authors.lastname: Weber
authors.forename: S P
authors.initials: SP
authors.lastname: Schantz
authors.forename: D M
authors.initials: DM
authors.lastname: Ota
authors.forename: M A
authors.initials: MA
authors.lastname: Schusterman
authors.forename: I H
authors.initials: IH
authors.lastname: Krakoff
authors.forename: J U
authors.initials: JU
authors.lastname: Gutterman
authors.forename: W K
authors.initials: WK
authors.lastname: Hong
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects; D015474:Isotretinoin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D012074:Remission Induction; D012878:Skin Neoplasms / Q000188:drug therapy*
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D015474:Isotretinoin