In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 23, No. 34 ( 2005-12-01), p. 8835-8844
Kurzfassung:
To evaluate the safety of sequentially administered recombinant (r) human (h) interleukin-12 (IL-12) and interferon alfa-2b (IFN-α-2b) in patients with advanced cancer and to determine the effects of endogenously produced IFN-γ on Janus kinase-signal transducer and activator of transcription (Jak-STAT) signal transduction in patient peripheral-blood mononuclear cells (PBMCs). Patients and Methods Forty-nine patients with metastatic cancer received rhIL-12 on day 1 and IFN-α-2b on days 2 to 6 of either a 14-day (n = 43) or a 7-day treatment cycle (n = 6). rhIL-12 was initially administered subcutaneously at a dose of 100 ng/kg, whereas IFN-α-2b was escalated from 1 to 10 million units (MU) in cohorts of three patients (1, 3, 5, 7, or 10 MU). rhIL-12 was subsequently administered intravenously (IV) in escalating doses (100 to 500 ng/kg) to achieve greater IFN-γ production. Peripheral blood was drawn for measurement of plasma IFN-γ and the induction of Jak-STAT signal transduction in PBMCs. Results No IL-12–or IFN-α–related dose-limiting toxicities were observed. There were no responses in 41 assessable patients. Five patients exhibited stable disease lasting 6 months or longer while on therapy. Optimal induction of IFN-γ by IL-12 occurred after an IV dose of 250 ng/kg. Patient PBMCs exhibited increased levels of STAT1 after IL-12 administration. The peak level of IFN-γ achieved with IL-12 therapy correlated with the peak level of intracellular STAT1 in patient PBMCs (r = 0.38, P = .021). Conclusion The combination of rhIL-12 and IFN-α-2b can be administered sequentially with minimal toxicity. IV administration of rhIL-12 modulates IFN-α–induced Jak-STAT signal transduction in patient PBMCs.
Materialart:
Online-Ressource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2005.02.1691
Sprache:
Englisch
Verlag:
American Society of Clinical Oncology (ASCO)
Publikationsdatum:
2005
ZDB Id:
2005181-5