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Titolo:
A 2-PART PHASE-I TRIAL OF HIGH-DOSE INTERLEUKIN-2 IN COMBINATION WITHSOLUBLE (CHINESE-HAMSTER OVARY) INTERLEUKIN-1 RECEPTOR
Autore:
MCDERMOTT DF; TREHU EG; MIER JW; SORCE D; RAND W; RONAYNE L; KAPPLER K; CLANCY M; KLEMPNER M; ATKINS MB;
Indirizzi:
BETH ISRAEL MED CTR,DIV ADULT HEMATOL ONCOL,330 BROOKLINE AVE,KIRSTEIN 1 BOSTON MA 02215 TUFTS UNIV,SCH MED,TUPPER RES INST,DIV HEMATOL ONCOL BOSTON MA 02215 TUFTS UNIV,SCH MED,TUPPER RES INST,DIV INFECT DIS BOSTON MA 02215 TUFTS UNIV NEW ENGLAND MED CTR BOSTON MA 02215
Titolo Testata:
Clinical cancer research
fascicolo: 5, volume: 4, anno: 1998,
pagine: 1203 - 1213
SICI:
1078-0432(1998)4:5<1203:A2PTOH>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
ACTIVATED KILLER-CELLS; METASTATIC MALIGNANT-MELANOMA; BLOOD MONONUCLEAR-CELLS; NECROSIS FACTOR-ALPHA; CONTINUOUS INFUSION INTERLEUKIN-2; IMMUNOPEROXIDASE TECHNIQUES; RECOMBINANT INTERLEUKIN-2; IL-1 RECEPTOR; FACTOR TNF; L-ARGININE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
39
Recensione:
Indirizzi per estratti:
Citazione:
D.F. Mcdermott et al., "A 2-PART PHASE-I TRIAL OF HIGH-DOSE INTERLEUKIN-2 IN COMBINATION WITHSOLUBLE (CHINESE-HAMSTER OVARY) INTERLEUKIN-1 RECEPTOR", Clinical cancer research, 4(5), 1998, pp. 1203-1213

Abstract

Our purpose was to determine the maximum tolerated dose and toxicity associated with soluble Chinese hamster ovary [s(CHO)] recombinant human interleukin (IL) I receptor (IL-1R; Immunex, Seattle, WA) administration in humans and to determine the effective biological dose and/or maximum tolerated dose of the s(CHO) IL-IR in combination with high-dose IL-2 as determined by reduction in IL-2 toxicity and modulation of its biological effects. Twenty-seven patients with metastatic cancer were treated with escalating doses of s(CHO) HL-1R at 1, 1, 5, 10, 20, 40, and 55 mg/m(2) i.v. on days -6 (except cohort 2), 1, and 15 and IL-2 at doses of 300,000 IU/kg (cohort 1) and 600,000 IU/kg (cohorts 2-7) i.v. every 8 h on days 1-5 and 15-19., No toxicity directly attributable to s(CHO) IL-1R was observed. The median number of IL-2 doses was23., Hypotension and neurotoxicity were the major dose-limiting toxicities for the IL-2/s(CHO) IL-1R combination. Of the 24 patients treated with full-dose IL-2, there were six responses, three complete and three partial (response rate, 25%). Three patients developed thyroid dysfunction, and all 3 responding melanoma patients exhibited vitiligo, The t(1/2),,, of s(CHO) IL-IR alone was 24-30 h and was not significantly altered by coadministration with IL-2, Whole-blood functional assays indicated that sufficient s(CHO) HL-1R was present in the circulation at top dose levels to inhibit the in vitro effects of IL-1 beta on IL-8 induction; however, no effect on IL-2-induced IL-8 induction, or on the IL-1 beta- or IL-2-induced tumor necrosis factor production, wasobserved. Suppression of IL-2-mediated tumor necrosis factor alpha and IL-6 induction in vivo during the first 24 h after IL-2 administration was observed, and the neutrophil chemotactic defect normally seen with IL-2 was not observed. IL-1R antagonist induction far exceeded that seen previously with IL-2 alone. No inhibition of either serum C-reactive protein induction or enhanced urinary nitrate excretion and no consistent effect on IL-2-related changes in peripheral blood mononuclear cell phenotype or endothelial adhesion molecule expression were seen. The coadministration of s(CHO) IL-IR produced no apparent reductionin IL-2 clinical toxicity manifested by either the ability to administer more IL-2 than anticipated or a reduction in the toxicity associated with a given amount of IL-2, Therefore, no effective biological dose could be identified for the s(CHO) IL-1R.

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Documento generato il 30/10/20 alle ore 09:13:50