Phase I and pharmacokinetic evaluation of intravenous hyaluronic acid in combination with doxorubicin or 5-fluorouracil.

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.