title: Circadian-based infusional chrono-chemotherapy controls progressive metastatic renal cell carcinoma.
abstract: We treated 25 patients with progressive metastatic renal cell carcinoma with continuous infusion of 5-fluoro-2-deoxyuridine (FUDR) by implanted pump. FUDR was infused for 14 days at monthly intervals. Starting dose was 0.15 mg/kg/day intravenous or 0.25 mg/kg/day intra-arterial; intravenous doses were increased or decreased in increments of 0.025 mg/kg/day as permitted by toxicity. Circadian time modification of the infusion shape (sinusoidal with the peak centered around 6 p.m.) significantly lowered serious intravenous infusion-associated toxicity, allowing higher dose intensity. In 24 evaluable patients, two complete responses (8%), six partial responses (25%), and one minor response were seen. One secondary partial response was observed after infusional velban (total objective response rate 37.5%). Previously progressive disease was controlled in greater than 80% of our patients. During a median follow-up period of 8 months (range of 2-26 months), the overall survival for all 25 patients is 75%. Our results indicate that metastatic renal cell cancer responds to infusional chemotherapy and that the circadian shape of infusion markedly affects our ability to deliver effective doses.
authors.affiliation: Department of Oncology, University of Minnesota Hospital and Clinic, Minneapolis 55455.
authors.forename: W J
authors.initials: WJ
authors.lastname: Hrushesky
authors.forename: R
authors.initials: R
authors.lastname: Von Roemeling
authors.forename: E E
authors.initials: EE
authors.lastname: Fraley
authors.forename: J T
authors.initials: JT
authors.lastname: Rabatin
mesh_terms: D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000556:secondary*; D002940:Circadian Rhythm; D004305:Dose-Response Relationship, Drug; D005260:Female; D005467:Floxuridine / Q000008:administration & dosage* / Q000633:toxicity; D006801:Humans; D007260:Infusion Pumps; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012074:Remission Induction; D014747:Vinblastine / Q000008:administration & dosage
chemical_list: D005467:Floxuridine; D014747:Vinblastine