title: A phase I safety study of doxifluridine and interferon-alpha-2a in patients with advanced neoplastic disease.
abstract: OBJECTIVE
  Doxifluridine (RO 21-9738, 5'-dFUR) is a fluoropyrimidine derivative with proven antitumor activity in different experimental models. On the basis of experimental evidence, several clinical trials have been carried out to define the optimal 5'-dFUR dose and route of administration. In general, the maximum monthly dose of 5'-dFUR was 36-38 g. According to these clinical data, we explored the feasibility of a combination of 5'-dFUR and interferon-alpha-2a (IFN-alpha-2a). The aim of the protocol was to confirm the maximum tolerated dose (MTD) of the drug in combination with a settled dose of IFN alpha 2a.
  
  
  METHODS
  An open-label phase I study with intravenous 5'-dFUR was carried out in 12 patients with a histologically proven diagnosis of advanced gastrointestinal or breast cancer refractory to previous conventional hormone-chemotherapy. Escalating doses of 5'-dFUR were administered as a 2-h intravenous infusion, once a week for at least 4 weeks in groups of 3 patients. IFN-alpha-2a was administered as an intramuscular injection of 3 MU 3 times a week for 4 consecutive weeks. Physical and laboratory parameters were assessed at baseline and then weekly until the end of treatment.
  
  
  RESULTS
  The treatment with 5'-dFUR was stopped at 5 g/m2, since this level corresponded to the maximum monthly dosage reported in the literature (36-38 g). No severe toxicity was recorded up to this drug level.
  
  
  CONCLUSIONS
  The combination of 5'-dFUR plus IFN-alpha-2a was well tolerated at the level of 5 g/m2. Although the MTD was not reached, it can be stated that the dosage administered in this study could be explored in a larger trial.
authors.affiliation: Servizio Oncologico, Ospedale S. Eugenio, Roma, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Antimi
authors.forename: L
authors.initials: L
authors.lastname: Majoli
authors.forename: M
authors.initials: M
authors.lastname: Minelli
authors.forename: C G
authors.initials: CG
authors.lastname: Stampino
authors.forename: A
authors.initials: A
authors.lastname: Pandolfi
authors.forename: G
authors.initials: G
authors.lastname: Papa
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D005260:Female; D005467:Floxuridine / Q000008:administration & dosage*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D011994:Recombinant Proteins
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D005467:Floxuridine; C025034:doxifluridine