Randomized multicenter phase II trial of subcutaneous recombinant human interleukin-12 versus interferon-α2a for patients with advanced renal cell carcinoma Journal Article
| Authors: | Motzer, R. J.; Rakhit, A.; Thompson, J. A.; Nemunaitis, J.; Murphy, B. A.; Ellerhorst, J.; Schwartz, L. H.; Berg, W. J.; Bukowski, R. M. |
| Article Title: | Randomized multicenter phase II trial of subcutaneous recombinant human interleukin-12 versus interferon-α2a for patients with advanced renal cell carcinoma |
| Abstract: | Recombinant human interleukin-12 (rHuIL-12) is a pleiotropic cytokine with anticancer activity against renal cell carcinoma (RCC) in preclinical models and in a phase I trial. A randomized phase II study of rHuIL-12 compared with interferon-α (IFN-α) evaluated clinical response for patients with previously untreated, advanced RCC. Patients were randomly assigned 2:1 to receive either rHuIL-12 or IFN-α2a. rHuIL-12 was administered by subcutaneous (s.c.) injection on days 1, 8, and 15 of each 28-day cycle. The dose of IL-12 was escalated during cycle 1 to a maintenance dose of 1.25 μg/kg. IFN was administered at 9 million units by s.c. injection three times per week. Serum concentrations of IL-12, IFN-γ, IL-10, and neopterin were obtained in 10 patients treated with rHuIL-12 after the first full dose of 1.25 μg/kg given on day 15 (dose 3) of cycle 1 and again after multiple doses on day 15 (dose 6) of cycle 2. Thirty patients were treated with rHuIL-12, and 16 patients were treated with IFN-α. Two (7%) of 30 patients treated with rHuIL-12 achieved a partial response, and the trial was closed to accrual based on the low response proportion. IL-12 was absorbed rapidly after s.c. drug administration, with the peak serum concentration appearing at approximately 12 h in both cycles. Serum IL-12 concentrations remained stable on multiple dosing. Levels of IFN-γ , IL-10, and neopterin increased with rHuIL-12 and were maintained in cycle 2. rHuIL-12 is a novel cytokine with unique pharmacologic and pharmacodynamic features under study for the treatment of malignancy and other medical conditions. The low response proportion associated with rHuIL-12 single-agent therapy against metastatic RCC was disappointing, given the preclinical data. Further study of rHuIL-12 for other medical conditions is underway. For RCC, the study of new cytokines is of the highest priority. |
| Keywords: | adult; clinical article; controlled study; aged; middle aged; human cell; clinical trial; neutropenia; ascites; dose response; metastasis; controlled clinical trial; phase 2 clinical trial; randomized controlled trial; stomatitis; interleukin 10; kidney carcinoma; kidney neoplasms; carcinoma, renal cell; multicenter study; recombinant proteins; alpha2a interferon; injections, subcutaneous; concentration response; blood level; interleukin-12; interferon alfa-2a; interleukin 12 receptor; humans; human; male; female; priority journal; article; neopterin |
| Journal Title: | Journal of Interferon and Cytokine Research |
| Volume: | 21 |
| Issue: | 4 |
| ISSN: | 1079-9907 |
| Publisher: | Mary Ann Liebert, Inc |
| Date Published: | 2001-04-01 |
| Start Page: | 257 |
| End Page: | 263 |
| Language: | English |
| DOI: | 10.1089/107999001750169934 |
| PUBMED: | 11359657 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 21 May 2015 -- Source: Scopus |
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