Phase I and Pharmacokinetic Evaluation of Intravenous Hyaluronic Acid in Combination with Doxorubicin or 5-Fluorouracil
2005 (English)In: Chemotherapy, ISSN 0009-3157, E-ISSN 1421-9794, Vol. 51, no 2-3, 132-141 p.Article in journal (Refereed) Published
BACKGROUND: Pre-clinically, hyaluronan (HA) has been demonstrated to systemically target chemotherapeutic drugs to tumours while ameliorating treatment toxicities. This study is a preliminary clinical investigation to determine if HA could be safely used in combination with 5-fluorouracil (5-FU) and doxorubicin (DOX). METHODS: Thirty patients with metastatic cancer were intravenously administered 500 mg/m2 HA in combination with escalating doses of DOX (30-60 mg/m2) or 5-FU (cumulative dose of 1,350-2,250 mg/m2 per cycle). The effect of pre-administration of 20 mg/m2 of folinic acid on HA/5-FU chemotherapy was also investigated. Patients were randomized to receive either HA/chemotherapy or chemotherapy alone in their first treatment cycle and vice versa for the second cycle. Patients received HA and chemotherapy in all subsequent cycles. RESULTS: Treatment was well tolerated, tumour responses were observed and the co-administration of HA did not alter the pharmacokinetics of clinically relevant doses of 5-FU or DOX. CONCLUSION: High doses of intravenous high-molecular-weight HA can be safely co-administered with clinical doses of chemotherapy without significantly altering the toxicity or pharmacokinetics of the drugs or HA.
Place, publisher, year, edition, pages
2005. Vol. 51, no 2-3, 132-141 p.
Adjuvants; Immunologic/administration & dosage/adverse effects/*pharmacokinetics, Adult, Aged, Antineoplastic Agents/administration & dosage/adverse effects/*pharmacokinetics, Comparative Study, Dose-Response Relationship; Drug, Doxorubicin/administration & dosage/adverse effects/*pharmacokinetics, Drug Therapy; Combination, Female, Fluorouracil/administration & dosage/adverse effects/*pharmacokinetics, Humans, Hyaluronic Acid/administration & dosage/adverse effects/*pharmacokinetics, Infusions; Intravenous, Leucovorin/pharmacology, Male, Middle Aged, Neoplasm Metastasis, Neoplasms/*drug therapy/pathology
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-74773DOI: 10.1159/000085621PubMedID: 15886473OAI: oai:DiVA.org:uu-74773DiVA: diva2:102683