Experience with the Use of High-Dose Interleukin-2 in the Treatment of 652 Cancer Patients

Abstract

We have administered 1039 courses of high-dose interleukin-2 (IL-2) to 652 cancer patients. Five hundred ninety-six patients had metastatic cancer that either had failed standard effective therapies or had disease for which no standard effective therapy existed, and 56 patients were treated in the absence of evaluable disease in the adjuvant setting. IL-2 was administered either alone (155 patients) or in conjunction with activated immune cells such as lymphokine activated killer (LAK) cells (214 patients) or tumor infiltrating lymphocytes (TIL) (66 patients), with other cytokines such as alpha interferon (a-IFN)(128 patients) or tumor necrosis factor (TNF)(38 patients), with monoclonal antibodies (32 patients), or with the chemotherapeutic agent cyclophosphamide (19 patients). Initial results with the treatment of high-dose IL-2 alone or in conjunction with LAK cells have indicated that objective regressions of cancer can be achieved in 20% to 35% of patients with selected advanced metastatic cancers. Although most responses have been seen in patients with metastatic renal cell cancer, melanoma, colorectal cancer, and non-Hodgkin's lymphoma, many histologic types of cancer have not been treated in significant numbers. These regressions can be durable; of 18 patients achieving a complete response, ten have not experienced recurrence at intervals from 18 to 52 months. Although combinations of IL-2 with TNF do not appear to result in increased responses, there is a suggestion in our initial phase I studies that the combination of a-IFN and IL-2 is more effective than the administration of cytokine alone and this combination deserves further study. Similarly the adoptive transfer of TIL in conjunction with IL-2 also appears to be more effective than the use of IL-2 alone. The toxic side effects in patients treated with high-dose IL-2 are presented and include malaise, nausea and vomiting, hypotension, fluid retention, and organ dysfunction. Treatment-related deaths were seen in 1% of all treatment courses and in 1.5% of patients. These studies demonstrate that a purely immunologic manipulation can mediate the regression of advanced cancers in selected patients and may provide a base for the development of practical, effective biologic treatments for some cancer patients.

Interleukin 2 therapy in cancer: identification of responders

“…At the cessation of rIL2 therapy, the CRP stimulation index was 31.3 ± 9.3 in the responders, and only 1.6 ± 0.3 in the non-responders (means ± s.e.m, P = 0.014). These (West et al, 1987;Rosenberg et al, 1989). It is, therefore, not surprising that attempts have been made to predict, at an early stage of therapy, which patients will subsequently respond to rIL2 therapy, but to date, it has not been possible to clearly identify these patients.…”

Subcutaneous low-dose recombinant interleukin 2 and alpha-interferon in patients with metastatic renal cell carcinoma

“…In patients with metastatic renal cell carcinoma, recombinant interleukin 2 (IL-2) administered either alone or in combination with lymphokine-activated killer (LAK) cells has given objective response rates of 16-35% (Rosenberg et al, 1987(Rosenberg et al, , 1989a; West et al, 1987;Fisher et al, 1988;Negrier et al, 1989;Dillman et al, 1991; Von der Maase et al, 1991). In most clinical studies, IL-2 was given either as an intravenous bolus (i.v.)…”

Biological therapy: approaches in colorectal cancer

“…Conventional treatments have largely relied on either interleukin 2 (IL-2) or adoptive IL-2-stimulated tumour infiltrating lymphocytes (TILs), with only sporadic reports of tumour regression (Rosenberg et al, 1989;Kradin et al, 1989). Recently, there has been a resurgence of interest in immunotherapy (and the potential of gene therapy) in advanced colorectal cancer and in an adjuvant setting.…”