Phase I trial of subcutaneous recombinant human interleukin-12 in patients with advanced renal cell carcinoma Journal Article
| Authors: | Motzer, R. J.; Rakhit, A.; Schwartz, L. H.; Olencki, T.; Malone, T. M.; Sandstrom, K.; Nadeau, R.; Parmar, H.; Bukowski, R. |
| Article Title: | Phase I trial of subcutaneous recombinant human interleukin-12 in patients with advanced renal cell carcinoma |
| Abstract: | Patients with advanced renal cell carcinoma were treated in a Phase I trial with escalating doses of recombinant human interleukin-12 (rHuIL-12) given on days 1, 8, and 15 of each 28-day cycle. Treatment in the initial dose scheme consisted of a fixed dose with dose levels of 0.1, 0.5, and 1.0 μg/kg given to cohorts composed of three or six patients. On the basis of the toxicity profile, a second scheme (up-titration) was undertaken wherein rHuIL-12 was escalated for each patient from week 1 to week 2, to a target dose given week 3 and thereafter; cohort target dose levels were 0.5, 0.75, 1.0, 1.25, and 1.5 μg/kg. Fifty-one patients were treated: 32 (63%) had prior cytokine therapy and 19 (37%) had received no prior systemic therapy. The maximum tolerated dose for the fixed dose scheme was 1.0 μg/kg. Dose- limiting toxicities included increase in transaminase concentration, pulmonary toxicity, and leukopenia. The most severe toxicities occurred with the first injection and were milder upon further treatment. With the up- titration dose scheme, the maximum tolerated dose was reached at 1.5 μg/kg, and dose-limiting toxicity consisted of an increase in serum transaminase levels. At the maximum tolerated dose of 1.5 μg/kg, serum IL-12 levels increased to a mean peak level of 706 pg/ml. Serum levels of IFN-γ increased to a mean peak level of about 200 pg/ml at 24 h after the first maintenance dose of 1.5 μg/kg. The best responses were as follows: one patient had complete response, 34 patients were stable, 14 patients showed progression, and 1 patient was inevaluable. In conclusion, rHuIL-12 was relatively well tolerated when administered by s.c. injection. The recommended dose according to the up-titration schedule of rHuIL-12 (μg/kg) for Phase II trials was as follows: cycle 1, 0.1 (day 1), 0.5 (day 8), 1.25 (day 15); cycle 2 onwards, 1.25. Phase II trials of rHuIL-12 were initiated in previously untreated patients with renal cell carcinoma and in patients with melanoma. |
| Keywords: | adolescent; adult; treatment outcome; aged; middle aged; major clinical study; clinical trial; advanced cancer; dose response; liver dysfunction; lung toxicity; leukopenia; kidney carcinoma; kidney neoplasms; carcinoma, renal cell; recombinant proteins; drug response; phase 1 clinical trial; injections, subcutaneous; interleukin-12; recombinant interleukin 12; humans; human; male; female; priority journal; article |
| Journal Title: | Clinical Cancer Research |
| Volume: | 4 |
| Issue: | 5 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 1998-05-01 |
| Start Page: | 1183 |
| End Page: | 1191 |
| Language: | English |
| PUBMED: | 9607576 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 12 December 2016 -- Source: Scopus |
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