Pilot study of the combination of sorafenib and fractionated irinotecan in pediatric relapse/refractory hepatic cancer (FINEX pilot study).
Pediatr Blood Cancer
; 67(11): e28655, 2020 11.
Article
in En
| MEDLINE
| ID: mdl-32798298
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/m2 every 12 hours or 400 mg/m2 every 24 hours daily combined with CPT-11 at 20 mg/m2 /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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Antineoplastic Combined Chemotherapy Protocols
/
Salvage Therapy
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Carcinoma, Hepatocellular
/
Drug Resistance, Neoplasm
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Liver Neoplasms
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Neoplasm Recurrence, Local
Type of study:
Guideline
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Child
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Child, preschool
/
Female
/
Humans
/
Infant
/
Male
Language:
En
Journal:
Pediatr Blood Cancer
Journal subject:
HEMATOLOGIA
/
NEOPLASIAS
/
PEDIATRIA
Year:
2020
Document type:
Article
Affiliation country:
Japan