A Phase I Study of High-Dose Interleukin-2 With Sorafenib in Patients With Metastatic Renal Cell Carcinoma and Melanoma
| Autor: | Thomas Olencki, Gregory B. Lesinski, Sanaa Tahiri, Kari Kendra, Amir Mortazavi, Thomas A. Mace, Susan Geyer, William E. Carson, Arvinder Bhinder, Steven K. Clinton, Elaine T. Lam, Paul Monk |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Sorafenib
Interleukin 2 Oncology Adult Male Niacinamide Cancer Research medicine.medical_specialty renal cell carcinoma Immunology urologic and male genital diseases high-dose interleukin 2 T-Lymphocytes Regulatory Flow cytometry Renal cell carcinoma Internal medicine Clinical Studies Antineoplastic Combined Chemotherapy Protocols medicine Carcinoma melanoma STAT5 Transcription Factor Immunology and Allergy Humans neoplasms Carcinoma Renal Cell Protein Kinase Inhibitors Aged Pharmacology medicine.diagnostic_test business.industry Melanoma Phenylurea Compounds Middle Aged medicine.disease Kidney Neoplasms Clinical trial Toxicity Interleukin-2 Female business medicine.drug |
| Zdroj: | Journal of Immunotherapy (Hagerstown, Md. : 1997) |
| ISSN: | 1537-4513 1524-9557 |
| Popis: | This study was designed to evaluate the safety and feasibility of high-dose interleukin-2 (HD IL-2) followed by sorafenib in patients with metastatic melanoma (MM) and renal cell carcinoma (RCC). Biomarkers relevant to the antitumor effects of IL-2 that may be altered by sorafenib including the percentages of natural T-regulatory cells (Tregs), myeloid-derived suppressor cells (MDSC), and STAT5 phosphorylation (pSTAT5) in T cells were evaluated. We hypothesized that the proposed treatment schedule is feasible and safe and may lead to enhanced tumor response. A phase I dose escalation trial was conducted in patients with either metastatic RCC or MM. HD IL-2 (600,000 IU/kg IV q8h × 8-12 doses) was administered on days 1-5 and 15-19, followed by sorafenib on days 29-82. The sorafenib dose was escalated. The percentage of Tregs, MDSC, and pSTAT5 in T cells were evaluated in peripheral blood by flow cytometry. Twelve of the 18 patients were evaluable for dose-limiting toxicity. No dose-limiting toxicity was observed. The treatment-related toxicity was predictable and did not seem to be additive with this schedule of administration. Partial responses were seen in 3 patients. No significant changes in the percentage of circulating Treg and MDSC were observed, whereas sorafenib did not adversely affect the ability of IL-2 to induce pSTAT5 in T cells. HD IL-2 followed by sorafenib was safe and feasible in patients with MM and RCC and did not adversely affect T-cell signaling through STAT5 in response to IL-2. |
| Databáze: | OpenAIRE |
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