title: Treatment of metastatic renal cell carcinoma with constant-rate floxuridine infusion plus recombinant alpha 2b-interferon.
abstract: BACKGROUND
  Floxuridine (FUDR) and alpha-interferon (IFN) are active agents in advanced renal cell carcinoma, with different dose-limiting toxic effects and antitumor synergism in experimental models. The main purpose of this phase II study was to assess the activity and toxic effects of a combination of FUDR and alpha 2b-IFN in metastatic renal cell carcinoma.
  
  
  METHODS
  Metastatic renal cell carcinoma patients with measurable disease entered the study. FUDR was administered as a constant-rate continuous infusion for 14 days every 28 days at a starting daily dose of 0.1 mg/kg and with dose escalations of 0.025 mg/kg/day at each subsequent cycle if WHO > or = 2 toxicity had not occurred. IFN-alpha 2b 10 x 10(6) I.U. was administered intramuscularly 3 times per week.
  
  
  RESULTS
  Forty-two patients entered the study and a total of 272 cycles of FUDR + alpha 2b-IFN were administered. In 41 evaluable patients WHO grade III-IV toxic effects included nausea and vomiting (22%), diarrhea (32%), stomatitis (12%), fatigue (27%) and anorexia (12%). It was possible to increase the initial FUDR does in 21 (50%) patients; the median FUDR dose intensity was 0.35 mg/kg/week (range 0.18-0.54). Among 39 evaluable patients, 3 (7.5%) complete and 10 (25.5%) partial responses were observed (response rate 33%, 95% confidence interval (CI) 19%-50%) which lasted a median of 13 months (5.5-40+). Responses also occurred in liver (2), in patients pretreated with systemic therapy (5) and in patients who had other unfavourable prognostic characteristics (7). Median progression-free and survival times were 9 and 16 months, respectively.
  
  
  CONCLUSIONS
  In this study FUDR + alpha 2b-IFN demonstrated interesting activity in metastatic renal cell carcinoma, showing promise also in patients with unfavourable prognostic characteristics. The antitumor activity of FUDR and alpha 2b-IFN seems to be cumulative, but cumulative toxicity is also observed. These results require confirmation in randomised trials.
authors.affiliation: U.O. Oncologia Medica, Ospedale S. Chiara, Pisa, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Falcone
authors.forename: C
authors.initials: C
authors.lastname: Cianci
authors.forename: E
authors.initials: E
authors.lastname: Pfanner
authors.forename: S
authors.initials: S
authors.lastname: Ricci
authors.forename: M
authors.initials: M
authors.lastname: Lencioni
authors.forename: I
authors.initials: I
authors.lastname: Brunetti
authors.forename: P C
authors.initials: PC
authors.lastname: Giulianotti
authors.forename: L
authors.initials: L
authors.lastname: Vannucci
authors.forename: F
authors.initials: F
authors.lastname: Mosca
authors.forename: P F
authors.initials: PF
authors.lastname: Conte
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D004334:Drug Administration Schedule; D004357:Drug Synergism; D005260:Female; D005467:Floxuridine / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D007273:Injections, Intramuscular; 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