Pilot study of the combination of sorafenib and fractionated irinotecan in pediatric relapse/refractory hepatic cancer (FINEX pilot study)

Abstract Background Preclinical observations suggested a synergistic effect of sorafenib (SFN) and irinotecan (CPT‐11) in hepatoblastoma (HB). Thus, we conducted a feasibility study of fractionated CPT‐11 combined with SFN to develop a new therapy against relapsed/refractory pediatric hepatic cancer (HC). Procedure The study was originally designed as a phase I, standard 3+3 dose‐finding study to evaluate dose‐limiting toxicities (DLTs) for the regimen and the optimal CPT‐11 dose in combination with SFN against relapsed/refractory pediatric HC, including HB and hepatocellular carcinoma (HCC). The enrolled patients received SFN at 200 mg/m 2 every 12 hours or 400 mg/m 2 every 24 hours daily combined with CPT‐11 at 20 mg/m 2 /day on days 1 to 5 as an initial level 1 dose. Results Six patients with HB ( n = 4) or HCC ( n = 2) were enrolled and treated with CPT‐11 dose level 1. The median age at enrollment was 8.7 (6.2‐16.3) years. All patients received platinum‐containing chemotherapy, and five or two patients received CPT‐11 or SFN before enrollment, respectively. Regimen toxicities were evaluable in all patients. One of six patients experienced a grade 4 transaminase levels increase, which was defined as a DLT per protocol. Grade 3/4 neutropenia and a grade 3 transaminase level increase occurred in three patients and one patient, respectively. All patients reported grade 1/2 toxicities such as anemia, skin toxicity, gastrointestinal symptoms, and hypoalbuminemia. Conclusions Although the study was terminated before determining the maximum‐tolerated CPT‐11 dose, SFN and CPT‐11 at the level 1 dose were concluded to be tolerable in pediatric patients with HC.