Abstract
Modulation of the immune response plays an important role in the natural history of renal cell carcinoma. Spontaneous regression of metastases has been well documented in a small percentage of patients after they undergo de-bulking nephrectomy without any additional systemic intervention. The only logical explanation for these observations is “resetting” of the balance between tumor and the host immune system that, having been overwhelmed by the tumor burden, is able to function better after tumor de-bulking. Attempts to modulate the activity of the immune system “on demand” have included the use of vaccines, cytokines/lymphokines, adoptive cell transfer, monoclonal antibodies and most recently manipulation of immune checkpoint inhibitors. Here we review the data for infusional interleukin-2 in the management of advanced renal cell carcinoma and its role in current clinical practice.
Highlights
Spontaneous regression of metastatic renal cell carcinoma has been reported in a small percentage of patients after de-bulking nephrectomy without any additional systemic intervention [1,2,3]
A large additional series published by Fyfe et al reported the outcomes of 255 patients with advanced renal cell carcinoma treated with high-dose bolus Interleukin 2 (IL-2) enrolled in 7 phase II studies at 21 institutions
VEGF TKIs, mTOR inhibitors and the combination of bevacizumab plus interferon have been approved for treatment of patients with metastatic renal cell carcinoma by the US FDA [34]
Summary
Spontaneous regression of metastatic renal cell carcinoma has been reported in a small percentage of patients after de-bulking nephrectomy without any additional systemic intervention [1,2,3]. A large additional series published by Fyfe et al reported the outcomes of 255 patients with advanced renal cell carcinoma treated with high-dose bolus IL-2 enrolled in 7 phase II studies at 21 institutions. The French immunotherapy intergroup conducted a randomized trial to compare low dose subcutaneous IL-2, interferon alpha 2a, the combination of the 2 cytokines and medroxyprogesterone in 492 patients with metastatic renal cell carcinoma of intermediate prognosis [26]. The goals of the PROCLAIM registry are to: (i), provide information regarding IL-2 and its prospective use; (ii), compare the difference in administration approaches for their respective effect on outcomes; (iii), validate efficacy of high-dose IL-2 on response and survival in the treatment of malignant diseases; (iv), identify patients and site-specific prognostic factors and (v), study and potentially guide the emergence of new therapeutic options in the immunological armamentarium. This observation suggests superior results in patients treated with high dose IL2 as first line therapy
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