Phase I study of elisidepsin (Irvalec®) in combination with carboplatin or gemcitabine in patients with advanced malignancies.

Details

Serval ID
serval:BIB_A685A39C7CF7
Type
Article: article from journal or magazin.
Collection
Publications
Title
Phase I study of elisidepsin (Irvalec®) in combination with carboplatin or gemcitabine in patients with advanced malignancies.
Journal
Investigational New Drugs
Author(s)
Goldwasser F., Faivre S., Alexandre J., Coronado C., Fernández-García E.M., Kahatt C.M., Paramio P.G., Dios J.L., Miguel-Lillo B., Raymond E.
ISSN
1573-0646 (Electronic)
ISSN-L
0167-6997
Publication state
Published
Issued date
2014
Peer-reviewed
Oui
Volume
32
Number
3
Pages
500-509
Language
english
Notes
Publication types: Clinical Trial, Phase I ; Journal Article ; Multicenter Study Publication Status: ppublish
Abstract
OBJECTIVE: To determine the maximum tolerated dose and the recommended dose (RD) for phase II trials of elisidepsin (Irvalec®) in combination with carboplatin or gemcitabine.
METHODS: Open-label, dose-escalating, two-arm, uncontrolled, phase I study. Patients received carboplatin on Day (D) 1, followed by elisidepsin on D1 and D8, every 3 weeks, or gemcitabine on D1 and D15, followed by elisidepsin on D1 and D15, every 4 weeks. A pharmacokinetic analysis was done from blood samples collected during the first treatment infusion.
RESULTS: Fifteen patients were treated with carboplatin/elisidepsin at doses from 4 AUC/1.0 mg flat dose (FD) to 5 AUC/2.5 mg FD. Two patients had dose-limiting toxicities (DLTs) at 5 AUC/2.0 mg, a dose delay >2 weeks due to grade-2 ALT increase and grade-3 thrombocytopenia, and a D8 infusion omission due to grade-3 ALT increase. The RD was established at 4 AUC/1.0 mg. Toxicity consisted mainly of mild-moderate anorexia, fatigue, and nausea. Twenty-two patients were treated with gemcitabine/elisidepsin at doses from 1,000 mg*m(2)/1.0 mg FD to 1,250 mg*m(2)/7.5 mg FD. Two patients had DLTs at 1,250 mg*m(2)/7.5 mg, both a D15 dose omission due to grade-2 ALT increase. The RD was defined at 1,250 mg*m(2)/5.0 mg. Toxicity consisted mainly of mild-moderate fatigue, pruritus, erythema, and myalgia. No objective response was observed. No relevant pharmacokinetic interaction was detected.
CONCLUSION: Infra-optimal doses of elisidepsin and carboplatin and a lack of antitumor activity despite using active drug concentrations in combination with gemcitabine do not warrant further clinical development for these two combinations.
Keywords
Adult, Aged, Antineoplastic Combined Chemotherapy Protocols/administration & dosage, Antineoplastic Combined Chemotherapy Protocols/adverse effects, Carboplatin/administration & dosage, Carboplatin/adverse effects, Deoxycytidine/administration & dosage, Deoxycytidine/adverse effects, Deoxycytidine/</QualifierName> <QualifierName MajorTopicYN="N" UI="Q000493">, Depsipeptides/administration & dosage, Depsipeptides/adverse effects, Female, Humans, Male, Maximum Tolerated Dose, Middle Aged, Neoplasms/blood, Neoplasms/drug therapy
Pubmed
Create date
11/02/2015 12:11
Last modification date
20/08/2019 15:11
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