A randomized phase II trial of intra-arterial chemotherapy using SM-11355 (Miriplatin) for hepatocellular carcinoma

作者：Okusaka Takuji^*; Kasugai Hiroshi; Ishii Hiroshi; Kudo Masatoshi; Sata Michio; Tanaka Katsuaki; Shioyama Yasukazu; Chayama Kazuaki; Kumada Hiromitsu; Yoshikawa Masaharu; Seki Toshihito; Saito Hidetugu; Hayashi Naoaki; Shiratori Keiko; Okita Kiwamu; Sakaida Isao; Honda Masao; Kusumoto Yukio; Tsutsumi Takuya; Sakata Kenji

来源：Investigational New Drugs, 2012, 30(5): 2015-2025.

DOI：10.1007/s10637-011-9776-4

• Iodized oil
• MIRIPLA
• Liver cancer
• Suspension
• Parallel study

Background SM-11355 is a platinum complex developed to treat hepatocellular carcinoma (HCC) via administration into the hepatic artery as a sustained-release suspension in iodized oil. We conducted a multicenter phase II trial in patients with HCC to evaluate the efficacy and safety of SM-11355, using a Zinostatin stimalamer suspension in iodized oil as a reference. Methods Patients with unresectable HCC were randomized 2:1 to receive administration of the SM-11355 or Zinostatin stimalamer suspension into the hepatic artery. A second injection was given 4-12 weeks later. Efficacy was evaluated by CT 3 months after treatment and categorized as therapeutic effect (TE) V to I, where TE V was defined as disappearance or 100% necrosis of all treated tumors. Results A total of 122 patients were evaluated for efficacy and toxicity (SM-11355, n = 83; Zinostatin stimalamer, n = 39). Baseline characteristics were similar in the two groups. The TE V rates were 26.5% (22/83) and 17.9% (7/39) in the SM-11355 and Zinostatin stimalamer groups, respectively. In the SM-11355 group,the most frequent drug-related adverse events (AEs) of a parts per thousand yenaEuro parts per thousand grade 3 were elevated AST, elevated ALT, thrombocytopenia, and hyperbilirubinemia. The AEs with the largest difference between the two groups (SM-11355 vs. Zinostatin stimalamer) were hepatic vascular injury (0 vs. 48.4%) and eosinophilia (84.3 vs. 41.0%). The 2-year and 3-year survival rates were 75.9% vs. 70.3% and 58.4% vs. 48.7%, respectively. Conclusions The results suggest that SM-11355 in iodized oil has similar efficacy to Zinostatin stimalamer and that repeated dosing of SM-11355 is possible without hepatic vascular injury in cases of relapse.

• 出版日期2012-10
• 单位中国医学科学院肿瘤医院