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Titolo:
Phase I trial of twice-weekly intravenous interleukin 12 in patients with metastatic renal cell cancer or malignant melanoma: Ability to maintain IFN-gamma induction is associated with clinical response
Autore:
Gollob, JA; Mier, JW; Veenstra, K; McDermott, DF; Clancy, D; Clancy, M; Atkins, MB;
Indirizzi:
Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA Beth Israel Deaconess Med Ctr Boston MA USA 02215 l, Boston, MA 02215 USA
Titolo Testata:
CLINICAL CANCER RESEARCH
fascicolo: 5, volume: 6, anno: 2000,
pagine: 1678 - 1692
SICI:
1078-0432(200005)6:5<1678:PITOTI>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
RECOMBINANT HUMAN INTERLEUKIN-12; STIMULATORY FACTOR NKSF; NATURAL-KILLER-CELLS; INTERFERON-GAMMA; T-CELLS; NITRIC-OXIDE; DENDRITIC CELLS; HUMAN MONOCYTES; DOWN-REGULATION; CYTOKINE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
46
Recensione:
Indirizzi per estratti:
Indirizzo: Gollob, JA Beth Israel Deaconess Med Ctr, Div Hematol Oncol, 330 BrooklineAve,E Campus-Room KS-158, Boston, MA 02215 USA Beth Israel Deaconess Med Ctr 330 Brookline Ave,E Campus-Room KS-158 Boston MA USA 02215
Citazione:
J.A. Gollob et al., "Phase I trial of twice-weekly intravenous interleukin 12 in patients with metastatic renal cell cancer or malignant melanoma: Ability to maintain IFN-gamma induction is associated with clinical response", CLIN CANC R, 6(5), 2000, pp. 1678-1692

Abstract

The aim of this study was to examine the tolerability, antitumor activity,and biological effects of a new schedule of i.v. recombinant human interleukin 12 (rhIL-12). Twenty-eight patients were enrolled in a Phase I trial in which rhIL-12 was administered twice weekly as an i.v. bolus for 6 weeks,Stable or responding patients were eligible to receive additional 6-week cycles until there was no evidence of disease or until tumor progression. Patient cohorts were treated with escalating doses of rhIL-12 (30-700 ng/kg). The maximum tolerated dose (MTD) was 500 ng/kg, with dose-limiting toxicities consisting of elevated hepatic transaminases and cytopenias. At the MTD(n = 14), there was one partial response occurring after 6 cycles of rhIL-12 in a patient with renal cell cancer. Two additional renal cell cancer patients treated at the MTD had prolonged disease stabilization, with one of these exhibiting tumor regression after 8 cycles of rhIL-12. IFN-gamma, IL-15, and IL-18 were induced in patients treated with rhIL-12. Whereas IFN-gamma and IL-15 induction were attenuated midway through the first cycle in patients with disease progression, those patients with tumor regression or prolonged disease stabilization were able to maintain IFN-gamma, IL-15, and IL-18 induction, The down-modulation of IFN-gamma induction during rhIL-12 treatment did not relate to IL-10 production or alterations in rhIL-12 bioavailability but was associated with an acquired defect in lymphocyte IFN-gamma production in response to IL-12, IL-2, or IL-15, This defect could be partially overcome in vitro through combined stimulation with IL-12 plus IL-2, These findings shaw that the chronic administration of twice-weekly i.v.rhIL-12 is well-tolerated, stimulates the production of IL-12 costimulatory cytokines and IFN-gamma, and can induce delayed tumor regression. Strategies aimed at maintaining IFN-gamma induction, such as the addition of IL-2,may further augment the response rate to this schedule of rhIL-12.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 19/09/20 alle ore 15:30:15