HEPATIC AND SEROLOGIC TOXICITY OF SYSTEMIC INTERLEUKIN-2 AND OR INTERFERON-ALPHA - EVIDENCE OF A RISK-BENEFIT ADVANTAGE OF SUBCUTANEOUS THERAPY

A total of 107 cancer patients were treated with 148 cycles of subcuta neous (SC) immunotherapy employing interleukin-2 (rIL-2) and/or interf eron-alpha (rIFN-alpha). The systemic toxicities of SC cytokine therap y were retrospectively evaluated with regard to hepatic and metabolic adverse effects, and compared to adverse effects previously reported u pon high- or intermediate-dose intravenous (IV) rIL-2 therapy. Our stu dy cohorts consisted of 15 patients who received SC rIL-2 at doses of 4.8-14.4 million IU/m2/day on 5 days per week for a total of 8 weeks, 20 patients who received rIFN-alpha2b at 3.0-6.0 million U/m2/day thri ce weekly for a total of 6 weeks, and 72 patients who were given SC rI FN-alpha2b at 6.0 million U/m2/day thrice weekly plus SC rIL-2 at 14.4 -18.0 million IU/m2/day on days 1 and 2, followed by 4.8 million IU/m2 /day, 5 days per week for 6 consecutive weeks. These treatment regimen s were well tolerated in the out-patient setting; no toxic deaths occu rred, and none of the patients developed life-threatening toxicity. Up on SC rIL-2/rIFN-alpha combination therapy, we observed mild decreases in plasma protein and albumin levels (mean nadir +/- standard deviati on, 67 +/- 5 g/L and 38.8 +/- 3.9 g/L, respectively), minor albeit sig nificant increases in serum total bilirubin levels (mean peak +/- stan dard deviation, 7.8 +/- 3.1 mumol/L), serum aspartate aminotransferase (25.9 +/- 9.9 U/L), alanine aminotransferase (42.0 +/- 45.9 U/L), alk aline phosphatase (301 +/- 255 U/L), lactate dehydrogenase (230 +/- 64 U/L), gamma-glutamyl transpeptidase (I 47 +/- 141 U/L) activities and triacylglyceride (2.6 +/- 0.9 mmol/L) concentrations. Cholinesterase activities (mean nadir +/- standard deviation, 42.6 +/- 13.7 kU/L), an d serum cholesterol levels (4.4 +/- 0.9 mmol/L) decreased upon SC rIL- 2/rIFN-alpha combination therapy. These mild clinical side effects and laboratory changes were in marked contrast to a multitude of dose-lim iting and life-threatening adverse reactions described upon IV rIL-2 t herapy. It is concluded that low- to intermediate-dose SC rIL-2/rIFN-a lpha combination therapy as used in this study, can be given in the ou tpatient setting with good practicability and excellent safety.