A pilot human evaluation of a formulation of irinotecan and hyaluronic acid in 5-fluorouracil-refractory metastatic colorectal cancer patients.

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. CONCLUSION: 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.