Chemoimmunotherapy using pegylated liposomal Doxorubicin and interleukin-18 in recurrent ovarian cancer: a phase I dose-escalation study.
Cancer Immunol Res
; 1(3): 168-78, 2013 Sep.
Article
em En
| MEDLINE
| ID: mdl-24777679
ABSTRACT
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.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Neoplasias Ovarianas
/
Protocolos de Quimioterapia Combinada Antineoplásica
/
Doxorrubicina
/
Interleucina-18
Tipo de estudo:
Clinical_trials
/
Guideline
/
Prognostic_studies
Limite:
Adult
/
Female
/
Humans
/
Middle aged
Idioma:
En
Revista:
Cancer Immunol Res
Ano de publicação:
2013
Tipo de documento:
Article