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. (c) 2008 S. Karger AG, Basel.
BACKGROUND: Preclinical data demonstrate that the polysaccharidehyaluronic 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 cancerpatients 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. (c) 2008 S. Karger AG, Basel.
Authors: Miranda P Ween; Katja Hummitzsch; Raymond J Rodgers; Martin K Oehler; Carmela Ricciardelli Journal: Clin Exp Metastasis Date: 2010-12-12 Impact factor: 5.150
Authors: Sun Joo Lee; Sukhen C Ghosh; Hee Dong Han; Rebecca L Stone; Justin Bottsford-Miller; De Yue Shen; Edmond J Auzenne; Alejandro Lopez-Araujo; Chunhua Lu; Masato Nishimura; Chad V Pecot; Behrouz Zand; Duangmani Thanapprapasr; Nicholas B Jennings; Yu Kang; Jie Huang; Wei Hu; Jim Klostergaard; Anil K Sood Journal: Clin Cancer Res Date: 2012-06-12 Impact factor: 12.531
Authors: Suniti Misra; Vincent C Hascall; Ilia Atanelishvili; Ricardo Moreno Rodriguez; Roger R Markwald; Shibnath Ghatak Journal: Int J Cell Biol Date: 2015-09-10