Phase I/II study of a fine-powder formulation of cisplatin for transcatheter arterial chemoembolization in hepatocellular carcinoma

Aim: The clinical feasibility of transcatheter arterial chemoembolization (TACE) with fine-powder cisplatin (CDDP) in patients with hepatocellular carcinoma (HCC) has not been investigated. A phase I/II study was conducted to investigate the safety and tolerability of fine-powder CDDP when it was used with lipiodol and gelatin sponge particles for TACE. Methods: Fine-powder CDDP emulsified in lipiodol was injected into tumor arteries. Embolization was subsequently performed with gelatin sponge particles. The CDDP dose was started at 45 mg/m2 (level 1) and increased to 65 mg/m2 in 10 mg/m2 increments. Results: Thirteen patients were enrolled in phase I study since no dose limiting toxicity was observed in any patients, even in seven patients at level 3 (65 mg/m2), the recommended dose was 65 mg/m2. The major adverse event was grade 3 thrombocytopenia, which occurred in 8% of patients. The incidence of hematological toxicities was 15% for leukocytopenia, 84% for thrombocytopenia, and 84% for anemia. Increased serum total bilirubin was observed in 54% and increased aspartate aminotransferase or alanine aminotransferase in all patients. All digestive tract symptoms (nausea 77%, anorexia 84%, vomiting 31%) were grade 2 or lower. Total adverse events were grade 3 or higher in 44%. The response rate in 19 patients who received the recommended dose was 21%. Conclusions: TACE with a fine-powder formulation of CDDP at a dose of 65 mg/m2 is well tolerated in patients with unresectable HCC.