A phase i study of high-dose interleukin-2 with sorafenib in patients with metastatic renal cell carcinoma and melanoma

Paul Monk, Elaine Lam, Amir Mortazavi, Kari Kendra, Gregory B. Lesinski, Thomas A. Mace, Susan Geyer, William E. Carson, Sanaa Tahiri, Arvinder Bhinder, Steven K. Clinton, Thomas Olencki

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8 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)180-186
Number of pages7
JournalJournal of Immunotherapy
Issue number3
StatePublished - Apr 2014


  • high-dose interleukin 2
  • melanoma
  • renal cell carcinoma
  • sorafenib

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology
  • Cancer Research


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