부산대학교 도서관

DHA-paclitaxel is a conjugate of paclitaxel and the fatty acid, docosahexaenoic acid. Preclinical studies have demonstrated increased activity, relative to paclitaxel, with the potential for an improved therapeutic ratio. We conducted a phase I study to determine the maximum tolerated doses of DHA-paclitaxel and carboplatin when administered in combination. Two cohorts of patients were treated: carboplatin AUC 5 with DHA-paclitaxel 660?mg?m-2 and carboplatin AUC 5 with DHA-paclitaxel 880?mg?m-2. Both drugs were given on day 1 every 21 days. A total of 15 patients were enrolled with a median age of 59 years (range 33-71). All patients had advanced cancer refractory to standard treatment, performance status 0-2 and were without major organ dysfunction. A total of 54 cycles of treatment were delivered. No dose-limiting toxicity (DLT) was seen in the first cohort of three patients. In an expanded second cohort, neutropenia was the main DLT, occurring in the first cycle of treatment in five of 12 patients: three of these patients and one additional patient also experienced dose-limiting grade 3 transient rises in liver transaminases. No alopecia was seen and one patient developed clinically significant neuropathy. One partial response was seen in a patient with advanced adenocarcinoma of the oesophago-gastric junction and 12 patients had stable disease with a median time to progression of 184 days (range 60-506 days). The recommended phase II dose in pretreated patients is Carboplatin AUC 5 and DHA-paclitaxel 660?mg?m-2 given every 21 days. Further studies with Carboplatin AUC 5 and DHA-paclitaxel 880?mg?m-2, given every 28 days, are warranted in chemo-naive patients.British Journal of Cancer (2004) 91, 1651-1655. doi:10.1038/sj.bjc.6602196 www.bjcancer.com Published online 19 October 2004 [ABSTRACT FROM AUTHOR]