In a phase I/II study, Stathopoulos GP et al evaluated the maximum tolerated dose of lipoplatin in combination with gemcitabine in patients with previously treated advanced pancreatic cancer (25). Lipoplatin was given as an 8-hour infusion followed by 60
minutes infusion of 1,000 mg/m2 of gemcitabine at day 1 and 15 every 28 days. The dose of lipoplatin was stepwise escalated from 25 mg/m2 to 125 mg/m2. Of the 24 enrolled patients, two of four patients at 125 mg/m2 experienced grade 3-4 neutropenia. Therefore, the MTD of lipoplatin in this combination was determined to be 100 mg/m2. In this dose escalating study, there were two (8.3%) partial responders Inhibitors,research,lifescience,medical and 14 (58.3%) disease stabilizers, and the median overall survival was 4 month. Further randomized phase II/III trial
against gemcitabine monotherapy is under evaluation. Liposome-entrapped cis-bisneodecanoato-trans-R,R-1,2-diaminocyclohexane Inhibitors,research,lifescience,medical (DACH) platinum(II) (L-NDDP, Aroplatin™) is a lipophilic cisplatin analog that has been formulated in relatively large-size Inhibitors,research,lifescience,medical multi-lamellar liposomes measuring from 1 to 3 µm in diameter. L-NDDP has been Tariquidar demonstrated to be non–cross-resistant with cisplatin in cisplatin-resistant Lovo DDP 3.0 (human colon cancer cells) and L1210/PPD (human leukemia cells) both in vitro and in vivo models. In a phase I study, L-NDDP was given intravenously once every 4 weeks, ranging from 7.5 mg/m2 to 390 mg/m2 (26). The infusion rate was set at 4 mg NDDP per minute for all cases. In this particular study, intra-patient dose escalation was allowed. Inhibitors,research,lifescience,medical Grade 1-2 nausea/vomiting, diarrhea and fever were frequently observed in patients receiving
100 mg/m2 or higher dose of L-NDDP. Six out of the 10 patients who had 390 mg/m2 experienced grade 4 hematological toxicities manifesting as thrombocytopenia, granulocytopenia or both. The MTD of Inhibitors,research,lifescience,medical intravenous L-NDDP every 4 weeks was determined as 300 mg/m2. In 2004, Aronex Pharmaceuticals had registered a phase I/II study of L-NDDP and gemcitabine combination in patients with advanced pancreatic cancer resistant to standard therapy in a public clinical trial registration website, the clinicaltrials.gov, with an indentifier of NCT00081549. Unfortunately, the latest trial information was updated in June 2005, and no further publication on this trial can be found. Liposomal STK38 Irinotecan (Nanoliposomal CPT-11, PEP02, MM-398) Irinotecan hydrochloride (CPT-11) is a water-soluble semi-synthetic derivative of camptothecin targeting topoisomerase I, and has been an approved agent for the treatment of metastatic colorectal cancer worldwide, and also for gastric cancer (Japan and Korea), non-small cell lung cancer, small cell lung cancer, cervical cancer, and non-Hodgkin’s lymphoma in Japan.