Satoru Sueyoshi

Transcatheter Arterial Chemoembolization Using Cisplatin Powder Mixed with Degradable Starch Microspheres for Colorectal Liver Metastases after FOLFOX Failure: Results of a Phase I/II Study

PURPOSE To report the results of a phase I/II study of a transcatheter arterial chemoembolization protocol using cisplatin powder and degradable starch microspheres (DSM) for unresectable colorectal liver metastases after failure of FOLFOX (5-flourouracil, leucovorin plus oxaliplatin) chemotherapy conducted to determine the recommended dose of cisplatin powder and to assess the efficacy and safety of the protocol. MATERIALS AND METHODS A fine-powder formulation of cisplatin was mixed with DSM and administered via the hepatic artery every 4 weeks. In phase I, three cohorts of patients received escalating doses of cisplatin powder: 50 mg/m(2), 65 mg/m(2), and 80 mg/m(2). In phase II, tumor response, toxicity, and survival times were assessed. RESULTS The study enrolled 24 patients. Previously, FOLFOX had been administered to all patients, an irinotecan-containing regimen had been administered to 12 patients, and bevacizumab or cetuximab or both had been administered to 14 patients. In phase I, dose-limiting toxicity did not appear at any level, and the recommended dose of cisplatin powder was determined to be 80 mg/m(2). In phase II, a tumor response rate of 61.1% was achieved. The median hepatic progression-free survival and overall survival were 8.8 months (95% confidence interval [CI], 4.06-13.5 mo) and 21.1 months (95% CI, 8.37-33.8 mo). The following grade 3 toxicities were observed: thrombocytopenia (12.5%), aspartate transaminase elevation (33.3%), alanine transaminase elevation (12.5%), hyponatremia (8.3%), and cholecystitis (4.2%). CONCLUSIONS This study shows that transcatheter arterial chemoembolization with cisplatin powder at a dose of 80 mg/m(2) mixed with DSM is well tolerated and can produce a high response rate with a long survival time for patients with unresectable colorectal liver metastases after failure of FOLFOX.

Pharmacokinetic Evaluation of Pancreatic Arterial Infusion Chemotherapy after Unification of the Blood Supply in an Animal Model

PURPOSE The purpose of this study was to investigate the potential pharmacokinetic advantage of pancreatic arterial infusion chemotherapy of 5-fluorouracil (5-FU) with temporary unification of the pancreatic blood supply for advanced pancreatic cancer in an animal model. MATERIALS AND METHODS Nine pigs were divided into three groups of three pigs each. 5-FU (20 mg/kg) was infused via jugular vein (group I), celiac artery (group II), and celiac artery with balloon occlusion of the superior mesenteric artery (SMA; group III). At 0, 10, 30, and 60 minutes after drug infusion, the concentrations of 5-FU were measured in plasma and tissues including the liver, pancreatic head, pancreatic uncinate process, and duodenum. Areas under the concentration-time curve (AUCs) were calculated and statistically compared. RESULTS The temporary unification of the pancreatic blood supply by converting from dual blood supply through the celiac artery and SMA into a single celiac arterial supply was confirmed by dye injection. Mean AUCs in the pancreas head and liver were significantly higher for groups II and III compared with group I (P < .05). In contrast, there were no significant differences in plasma 5-FU concentrations between groups. In addition, the AUC in the pancreatic uncinate process was significantly higher for group III compared with groups I and II (P < .05). CONCLUSIONS Pancreatic arterial infusion chemotherapy allows efficient regional drug delivery into the pancreas and liver. Importantly, the unification of the pancreatic blood supply may be required to induce maximum efficacy of arterial infusion chemotherapy for the tumor in the pancreatic uncinate process.

Hepatic Arterial Infusion Chemotherapy Combined with Venous Embolization in a Patient with Hepatic Metastases with an Arteriovenous Shunt

We describe herein a patient who had hepatic metastases with an arteriovenous shunt and was treated by hepatic arterial infusion chemotherapy. The arteriovenous shunt was diagnosed by 99mTc-macroaggregated albumin scintigraphy and hepatic venous embolization was performed to reduce shunt flow.