Titre
Chemoimmunotherapy using pegylated liposomal Doxorubicin and interleukin-18 in recurrent ovarian cancer: a phase I dose-escalation study.
Type
article
Institution
Externe
Périodique
Auteur(s)
Simpkins, F.
Auteure/Auteur
Flores, A.
Auteure/Auteur
Chu, C.
Auteure/Auteur
Berek, J.S.
Auteure/Auteur
Lucci, J.
Auteure/Auteur
Murray, S.
Auteure/Auteur
Bauman, J.
Auteure/Auteur
Struemper, H.
Auteure/Auteur
Germaschewski, F.
Auteure/Auteur
Jonak, Z.
Auteure/Auteur
Gardner, O.
Auteure/Auteur
Toso, J.
Auteure/Auteur
Coukos, G.
Auteure/Auteur
Liens vers les personnes
ISSN
2326-6074
Statut éditorial
Publié
Date de publication
2013
Volume
1
Numéro
3
Première page
168
Dernière page/numéro d’article
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.
PID Serval
serval:BIB_C0BBE1B32486
PMID
Open Access
Oui
Date de création
2014-10-14T10:42:42.409Z
Date de création dans IRIS
2025-05-21T00:47:05Z