Abstract | PURPOSE:
BAY 50-4798 is an analogue of interleukin-2 that selectively activates T cells over natural killer cells. This phase I study was designed to determine the maximum tolerated dose (MTD) and safety of BAY 50-4798, screen for tumor response, and assess pharmacokinetics. EXPERIMENTAL DESIGN: Forty-five patients with metastatic melanoma or renal cancer were enrolled, 31 on escalating doses to determine the MTD, with 20 renal cell carcinoma patients treated at MTD to detect antitumor activity. BAY 50-4798 was delivered i.v. every 8 h, days 1 to 5 and 15 to 19, and could be repeated after 9 weeks if tumor was stable or responding. RESULTS: The MTD was defined by and reported in terms of doses received. The doses tested ranged from 1.3 to 26.1 microg/kg, and the MTD was defined as 10.4 microg/kg based on toxicities similar to those of aldesleukin. Two patients achieved partial responses, one with melanoma and one with renal cell carcinoma. Among all 45 patients, 53% and 9% experienced a grade 3 and 4 toxicity, respectively. Among the patients treated at the MTD of 10.4 microg/kg, 71% and 10% experienced a grade 3 and 4 toxicity, respectively. Pharmacokinetics showed dose-dependent peak concentrations (C(max)) and area under the curve with a half-life of approximately 2 h and no evidence of accumulation. Lymphocyte subset analysis confirmed the preferential expansion of T-cell subsets over natural killer cells. CONCLUSIONS:
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Authors | Kim Margolin, Michael B Atkins, Janice P Dutcher, Marc S Ernstoff, John W Smith 2nd, Joseph I Clark, Joseph Baar, Jeffrey Sosman, Jeffrey Weber, Chetan Lathia, Janice Brunetti, Frank Cihon, Brian Schwartz |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 13
Issue 11
Pg. 3312-9
(Jun 01 2007)
ISSN: 1078-0432 [Print] United States |
PMID | 17545537
(Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Interleukin-2
- Recombinant Proteins
- aldesleukin
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Topics |
- Adult
- Aged
- Aged, 80 and over
- Antineoplastic Agents
(pharmacology)
- Dose-Response Relationship, Drug
- Female
- Humans
- Interleukin-2
(agonists, analogs & derivatives, therapeutic use)
- Kidney Neoplasms
(drug therapy, metabolism)
- Lymphocyte Subsets
(metabolism)
- Male
- Melanoma
(drug therapy, metabolism)
- Middle Aged
- Recombinant Proteins
(therapeutic use)
- Skin Neoplasms
(drug therapy, metabolism)
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