Clinical application of continuous infusion of recombinant interleukin-2.

Abstract

While preclinical studies suggest a steep dose-response relationship for the anti-cancer effect of recombinant interleukin-2 (rIL-2), translation of dose-intense rIL-2 to humans can be complicated by known toxicities, including hypotension, capillary leak phenomena and fluid retention. In an attempt to develop a manageable approach to dose-intense rIL-2, we have employed a continuous infusion schedule, 18 X 10(6) IU rIL-2/m2/day for five days. This treatment results in marked biological effect, and continuous infusion of rIL-2 alone or in conjunction with lymphokine-activated killer cells can result in complete remission of metastatic renal carcinoma. Treatment with continuous infusion tumour necrosis factor at 60 micrograms/m2/day for three days prior to rIL-2 may be of possible benefit in isolated cases of colon and lung carcinoma, but has not appeared to produce results superior to rIL-2 alone. Addition of tumour-infiltrating lymphocytes has been of benefit in selected cases of melanoma. The most promising combination of biological agents may be rIL-2 in conjunction with alpha-interferon. Ongoing studies involving subcutaneous alpha-interferon during continuous infusion rIL-2 suggest clinical synergy with acceptable toxicity.