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

• Published in: Investigational new drugs 2012-10, Vol.30 (5), p.2015-2025
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Aged; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - metabolism; Drug Administration Schedule; Female; Hepatic Artery; Humans; Infusions, Intra-Arterial - methods; Liver Neoplasms - drug therapy; Liver Neoplasms - metabolism; Male; Medicine; Medicine & Public Health; Middle Aged; Oncology; Organoplatinum Compounds - administration & dosage; Organoplatinum Compounds - adverse effects; Organoplatinum Compounds - pharmacokinetics; Pharmacology/Toxicology; Phase II Studies; Survival Rate
• ISSN: 0167-6997; 1573-0646
• DOI: 10.1007/s10637-011-9776-4

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 ≥ 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.