title: Alpha-2B-interferon plus floxuridine in metastatic renal cell carcinoma. A phase I-II study.
abstract: BACKGROUND
  Both alpha-interferon and floxuridine are active in metastatic renal cell carcinoma (MRCC); the two agents have demonstrated antitumor synergism and different clinical toxicities. The purpose of this study was to determine the maximum tolerable dose (MTD) of floxuridine (FUDR), administered as a constant continuous infusion for 14 days every 28 days, in combination with fixed doses of alpha-2B-interferon and to preliminarily evaluate the antitumor activity of this combination.
  
  
  METHODS
  Sixteen patients entered the study; six had previously received alpha-interferon. Alpha-2B-interferon was administered at the dose of 10 x 10(6) IU intramuscularly 3 times/week and floxuridine at the starting daily dose of 0.075 mg/kg. This dose was escalated at each subsequent cycle up to dose-limiting toxicity.
  
  
  RESULTS
  Most common toxicities included fever and flue-like symptoms, fatigue, anorexia, diarrhea, mucositis, and nausea, and 55% of patients experienced greater than or equal to Grade 2 toxicity, mostly diarrhea, for floxuridine doses greater than 0.125 mg/kg/d. Among 15 evaluable patients, 1 achieved a complete response and 4 achieved a partial one (33%; 95% confidence interval, 12-62%). Three partial responses were obtained in patients pretreated with alpha-interferon plus vinblastine.
  
  
  CONCLUSIONS
  The combination of alpha-2B-interferon and floxuridine is feasible, and in our regimen the recommended daily dose of floxuridine for Phase II studies was 0.125 mg/kg. This combination is active in metastatic renal carcinoma, but further studies are needed to determine whether alpha-2B-interferon has added anything to the FUDR infusion or vice versa.
authors.affiliation: Division of Medical Oncology, S. Chiara Hospital, Pisa, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Falcone
authors.forename: C
authors.initials: C
authors.lastname: Cianci
authors.forename: S
authors.initials: S
authors.lastname: Ricci
authors.forename: I
authors.initials: I
authors.lastname: Brunetti
authors.forename: M
authors.initials: M
authors.lastname: Bertuccelli
authors.forename: P F
authors.initials: PF
authors.lastname: Conte
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D005260:Female; D005467:Floxuridine / Q000008:administration & dosage / Q000633:toxicity*; D006801:Humans; D015918:Infusion Pumps, Implantable; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011994:Recombinant Proteins
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D005467:Floxuridine