title: A phase I study of the trinuclear platinum compound, BBR 3464, in combination with protracted venous infusional 5-fluorouracil in patients with advanced cancer.
abstract: OBJECTIVE
  BBR 3464 is a novel trinuclear platinum anticancer agent with a broad spectrum of preclinical antitumour activity. A phase I, open-label dose-escalating study was performed to determine the maximum tolerated dose (MTD) of BBR 3464 administered in combination with protracted venous infusional (PVI) 5-fluorouracil (5-FU) for up to six courses in patients with locally advanced and/or metastatic cancer.
  
  
  METHODS
  Dose escalation was based on observation of toxicity at each dose level. BBR 3464 (0.6 mg/m(2) escalated to 0.75 mg/m(2)) was studied in combination with PVI 5-FU (200 mg/m(2) per day).
  
  
  RESULTS
  Entered into the study were 14 patients. The most frequent toxicities were nausea, neutropenia, fatigue and diarrhoea. The protocol-defined MTD was not determined as 11/14 patients experienced grade 3 or 4 neutropenia that interrupted the planned administration of PVI 5-FU on day 15 (of 21). Although these events were not dose-limiting, as defined in the protocol, they imposed limitations on the dose of PVI 5-FU administered. Antitumour activity was observed: a partial response in one patient (7%) with invasive breast cancer. Stable disease was confirmed in three patients (21%). These four patients all completed the planned six courses of combined therapy.
  
  
  CONCLUSIONS
  In light of the lack of septic events associated with the recorded neutropenia, it may be possible to safely continue PVI 5-FU despite the grade 3 or 4 neutropenia or modify the PVI schedule and administer therapy on days 1-15 of the 21-day cycle, but these modifications were not considered in this study.
authors: Edinburgh Cancer Research Centre, Western General Hospital, Crewe Road, Edinburgh, UK.
authors: Charlie
authors: C
authors: Gourley
authors: James
authors: J
authors: Cassidy
authors: Chris
authors: C
authors: Edwards
authors: Leslie
authors: L
authors: Samuel
authors: Donald
authors: D
authors: Bisset
authors: Gabriella
authors: G
authors: Camboni
authors: Anne
authors: A
authors: Young
authors: Dorothy
authors: D
authors: Boyle
authors: Duncan
authors: D
authors: Jodrell
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003967:Diarrhea / Q000139:chemically induced / Q000453:epidemiology; D005221:Fatigue / Q000139:chemically induced / Q000453:epidemiology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006402:Hematologic Diseases / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced / Q000453:epidemiology; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009944:Organoplatinum Compounds / Q000008:administration & dosage
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C114062:BBR 3464; D005472:Fluorouracil