Update on the Role of Interleukin 2 and Other Cytokines in the Treatment of Patients with Stage IV Renal Carcinoma

Abstract

Immunoreactive cytokines have been the mainstay of treatment of renal cancer for the past 15 years. Most research has focused on interferon alpha (IFN-␣) and interleukin 2 (IL-2). IFN-␣ has been shown in Phase III studies to produce a modest survival advantage over inactive or non-IFN-containing regimens. Its general tolerability, multiple proposed mechanisms of action, and familiarity have prompted IFN-␣ to be studied in combination with a variety of agents with potential activity against renal cell carcinoma. These various studies may justify an increased role for IFN-␣ in the treatment of renal cancer in the foreseeable future. High-dose bolus IL-2 remains the only treatment for stage IV renal cancer approved by the United States Food and Drug Administration. Food and Drug Administration approval was granted in 1992 based on the ability of this agent to produce durable complete responses in a small number of patients. Unfortunately, the toxicity, expense, and restricted accessibility of high-dose IL-2 make it a poor standard. Regimens involving lower doses of IL-2 either alone or in combination with IFN-␣ have generally produced fewer tumor regressions of less overall quality. Recent efforts have focused on trying to identify factors predictive of response to IL-2 therapy so that this treatment could be limited to those most likely to benefit.

Perioperative immunomodulation with interleukin-2 in patients with renal cell carcinoma: results of a controlled phase II trial

“…It also suggests that the survival data reported here are not corrupted by subsequent systemic immunotherapy. Tumour-specific survival in the control group is comparable with that recently reported by other groups (Motzer et al, 1999;Flanigan et al, 2001;Mickisch et al, 2001;Atzpodien et al, 2003;Verra et al, 2003;Atkins et al, 2004), suggesting that a representative and reliable patient population was assessed here.…”

Prostaglandin E2 Regulates Renal Cell Carcinoma Invasion through the EP4 Receptor-Rap GTPase Signal Transduction Pathway

“…Majority of kidney cancer-related deaths result from cancer metastasis to distal organs and the prognosis of patients with metastatic disease is poor with a median survival of 10 months (4,42,43). Although surgery is highly effective for the treatment of localized low-grade RCC (43), current management options of patients diagnosed with locally advanced or metastatic kidney cancer are not curative, reinforcing the need to identify mechanisms involved in kidney cancer initiation, survival, and metastasis as a prerequisite for discovering effective therapeutics.…”

New Perspectives on the Treatment of Metastatic Renal Cell Carcinoma: An Introduction and Historical Overview

“…Until recently, patients with RCC whose disease had metastasized had few treatment options. Cytokines (interleukin-2 and interferon-␣) were the standard therapy but were associated with relatively low response rates and significant toxicity [5][6][7].…”