Transarterial Infusion Chemotherapy with Cisplatin Plus S-1 for Treating Hepatocellular Carcinoma: Results of a Phase I Trial

ABSTRACT Background In Japan, transarterial infusion chemotherapy (TAI) with cisplatin (CDDP) is used for advanced hepatocellular carcinoma (HCC) patients, and the response rate (RR) was 33.8% in previous phase (P) II study. S-1, oral systematic chemotherapy, is also promised for advanced HCC patients, and achieved 23.1% RR in previous P-II study. The clinical feasibility and efficacy of CDDP for TAI plus S-1 in patients with advanced HCC has not yet been investigated. Thus, we carried out this trial to determine the recommended dose (RD). Methods Although 13 Child-Pugh class A or B patients with advanced HCC entered themselves for this P-I trial, one patient of them was excluded from this trial due to the breach of criteria. The patients received TAI with CDDP (infusion on day 1 of the courses) plus S-1 (daily oral administration on days 1–21 of the courses), every 5 weeks until disease progression. Results Three dose levels were used for the 12 patients. Dose-limiting toxicity was not observed in three patients at level 1 (CDDP; 65 mg/m2 and S-1; 60 mg/m2), three patients at level 2 (CDDP; 65 mg/m2 and S-1; 80 mg/m2), and seven patients at level 3 (CDDP; 65 mg/m2 and S-1;100 mg/m2); therefore, the RDs for CDDP and S-1 were considered to be 65 and 100 mg/m2, respectively (level 3). Grade 3 adverse events were reported for 10 patients and were considered to be related to the study drugs for six patients: two patients, increased alanine aminotransferase level; two patients, increased aspartate aminotransferase level; one patient, anemia; and 1 patient, decreased platelet count. The total number of treatment courses was 25, with a mean of 1.5 courses per patient (range, 1–6 courses). The median progression-free survivaltime was 73 days. The disease control rate was 58% (7 of 12); two patients (16%) achieved partial response and five (42%) had stable disease. Conclusions TAI with CDDP plus S-1 can be used safely with promising tumor control for treating advanced HCC. The RD to be used for a P-II study of this regimen was determined to be level 3.