Idarubicin-loaded beads for chemoembolisation of hepatocellular carcinoma: results of the IDASPHERE phase I trial.
Aliment Pharmacol Ther
; 39(11): 1301-13, 2014 Jun.
Article
in En
| MEDLINE
| ID: mdl-24738629
ABSTRACT
BACKGROUND:
A phase I dose-escalation trial of transarterial chemoembolisation (TACE) with idarubicin-loaded beads was performed in cirrhotic patients with hepatocellular carcinoma (HCC).AIM:
To estimate the maximum-tolerated dose (MTD) and to assess safety, efficacy, pharmacokinetics and quality of life.METHODS:
Patients received a single TACE session with injection of 2 mL drug-eluting beads (DEBs; DC Bead 300-500 µm) loaded with idarubicin. The idarubicin dose was escalated according to a modified continuous reassessment method. MTD was defined as the dose level closest to that causing dose-limiting toxicity (DLT) in 20% of patients.RESULTS:
Twenty-one patients were enrolled, including nine patients at 5 mg, six patients at 10 mg, and six patients at 15 mg. One patient at each dose level experienced DLT (acute myocardial infarction, hyperbilirubinaemia and elevated aspartate aminotransferase (AST) at 5-, 10- and 15-mg, respectively). The calculated MTD of idarubicin was 10 mg. The most frequent grade ≥3 adverse events were pain, elevated AST, elevated γ-glutamyltranspeptidase and thrombocytopenia. At 2 months, the objective response rate was 52% (complete response, 28%, and partial response, 24%) by modified Response Evaluation Criteria in Solid Tumours. The median time to progression was 12.1 months (95% CI 7.4 months--not reached); the median overall survival was 24.5 months (95% CI 14.7 months--not reached). Pharmacokinetic analysis demonstrated the ability of DEBs to release idarubicin slowly.CONCLUSIONS:
Using drug-eluting beads, the maximum-tolerated dose of idarubicin was 10 mg per TACE session. Encouraging responses and median time to progression were observed. Further clinical investigations are warranted (NCT01040559).
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Idarubicin
/
Chemoembolization, Therapeutic
/
Carcinoma, Hepatocellular
/
Liver Neoplasms
Aspects:
Patient_preference
Limits:
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Aliment Pharmacol Ther
Journal subject:
FARMACOLOGIA
/
GASTROENTEROLOGIA
/
TERAPIA POR MEDICAMENTOS
Year:
2014
Document type:
Article
Affiliation country:
Francia