title: A pilot human evaluation of a formulation of irinotecan and hyaluronic acid in 5-fluorouracil-refractory metastatic colorectal cancer patients.
abstract: BACKGROUND
  Preclinical data demonstrate that the polysaccharide hyaluronic acid (HA) acts as a macromolecular carrier for chemotherapeutic drugs. In these studies the formulation of HA and irinotecan reduced treatment-related toxicity and improved efficacy via the preferential delivery of irinotecan to the tumor and lymph nodes. This study was designed as a first-in-man investigation of the safety and pharmacokinetics of irinotecan when administered within the HA-Irinotecan formulation.
  
  
  METHODS
  5-Fluorouracil refractory metastatic colorectal cancer patients were intravenously treated with HA-Irinotecan (300 mg/m(2) irinotecan with 1,000 mg/m(2) HA) on day 1 of a 21-day cycle. After safety was demonstrated, the irinotecan dose was increased to 350 mg/m(2) with maintenance of the HA at 1,000 mg/m(2).
  
  
  RESULTS
  Twelve patients were treated with HA-Irinotecan. Overall toxicity was low, with an 8 and 17% incidence of grade lll/lV diarrhea and neutropenia, respectively. No grade III/IV nausea or vomiting was observed. Seventeen percent of patients had a partial response and 50% experienced stable disease, indicating that the efficacy of the irinotecan was maintained. Median survival was 16.6 months, while median progression-free survival was 6.2 months.
  
  
  CONCLUSIONS
  HA-Irinotecan containing standard doses of irinotecan can be safely administered to patients. Comparison to historical irinotecan data suggests HA-Irinotecan may have a greater margin of safety without compromising anticancer activity.
authors.affiliation: Department of Medical Oncology and Haematology, Royal Melbourne Hospital, Melbourne, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Gibbs
authors.forename: Tracey J
authors.initials: TJ
authors.lastname: Brown
authors.forename: Raymond
authors.initials: R
authors.lastname: Ng
authors.forename: Ross
authors.initials: R
authors.lastname: Jennens
authors.forename: Edith
authors.initials: E
authors.lastname: Cinc
authors.forename: Minh
authors.initials: M
authors.lastname: Pho
authors.forename: Michael
authors.initials: M
authors.lastname: Michael
authors.forename: Richard M
authors.initials: RM
authors.lastname: Fox
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000633:toxicity; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004337:Drug Carriers; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D010865:Pilot Projects; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D000077146:Irinotecan; D006820:Hyaluronic Acid; D005472:Fluorouracil; D002166:Camptothecin