Recombinant IL-2 given intra-splenically and intravenously in advanced malignant melanoma: A phase I/II study

Abstract

High dose recombinant interleukin-2 (rIL-2) ei th er alone or in association with LAK cell preparations has produced tumor regressions in patients with metastatic cancer. These tumour regressions were remarkable given that the patients had either failed on standard therapy or no standard therapy was available (1). Th e median cumulative dose of rIL-2 used was 1.8 x lo6 U/kg; the rIL-2 being given every 8 h over two 5-day periods. A recent update reported six partial responses in 23 advanced melanoma patients (2). However, considerable toxicity was encountered with the high dose regimen of rIL-2 when given alone. This toxicity was presumed to be mainly due to increased capillary permeability. Side effects included hypotension requiring pressers on 64% ofcourses, respiratory distress sometimes needing intubation on 2 l%, encephalopathy on 18%, nausea with vomiting and diarrhoea on 87% of courses. Marked abnormalities in renal, hepatic and haematological parameters were also noted, with death from toxicity in three of49 patients with advanced cancer. New approaches to the treatment of advanced melanoma are urgently needed, given the lack of any worthwhile standard therapy and the increasing incidence of this malignancy. The important studies of Rosenberg and co-workers led us to develop a novel method of rIL-2 administration. The first dose being given via the splenic artery in an attempt to stimulate putative LAK cell precursors concentrated in that organ followed by alternate day intravenous doses.