Chemoimmunotherapy using pegylated liposomal Doxorubicin and interleukin-18 in recurrent ovarian cancer: a phase I dose-escalation study.
Détails
ID Serval
serval:BIB_C0BBE1B32486
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Chemoimmunotherapy using pegylated liposomal Doxorubicin and interleukin-18 in recurrent ovarian cancer: a phase I dose-escalation study.
Périodique
Cancer Immunology Research
ISSN
2326-6074 (Electronic)
Statut éditorial
Publié
Date de publication
2013
Volume
1
Numéro
3
Pages
168-178
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
Recombinant interleukin (IL)-18 (SB-485232) is an immunostimulatory cytokine, with shown antitumor activity in combination with pegylated liposomal doxorubicin (PLD) in preclinical models. This phase I study evaluated the safety, tolerability, and biologic activity of SB-485232 administered in combination with PLD in subjects with recurrent ovarian cancer. The protocol comprised four cycles of PLD (40 mg/m(2)) on day 1 every 28 days, in combination with SB-485232 at increasing doses (1, 3, 10, 30, and 100 μg/kg) on days 2 and 9 of each cycle, to be administered over five subject cohorts, followed by discretionary PLD monotherapy. Sixteen subjects were enrolled. One subject withdrew due to PLD hypersensitivity. Most subjects (82%) were platinum-resistant or refractory, and had received a median of three or more prior chemotherapy regimens. SB-485232 up to 100 μg/kg with PLD had an acceptable safety profile. Common drug-related adverse events were grade 1 or 2 (no grade 4 or 5 adverse events). Concomitant PLD administration did not attenuate the biologic activity of IL-18, with maximal SB-485232 biologic activity already observed at 3 μg/kg. Ten of 16 enrolled subjects (63%) completed treatment, whereas five (31%) subjects progressed on treatment. A 6% partial objective response rate and a 38% stable disease rate were observed. We provide pilot data suggesting that SB-485232 at the 3 μg/kg dose level in combination with PLD is safe and biologically active. This combination warrants further study in a phase II trial.
Pubmed
Web of science
Open Access
Oui
Création de la notice
14/10/2014 12:42
Dernière modification de la notice
20/08/2019 16:35