INTRALESIONAL CYTOKINE THERAPY IN CANCER - A PILOT-STUDY OF GM-CSF INFUSION IN MESOTHELIOMA

Systemic cytokine therapy in cancer has major side effects, and we rea soned that the local infusion of cytokines into turners could induce l ocal immunologic responses with minimal toxicity and potentially stron g systemic anticancer effects. This study investigated the toxicity an d effectiveness of intralesional granulocyte/macrophage-colony-stimula ting factor (GM-CSF) infusion in solid-tumor masses. We studied 14 pat ients (12 men, two women) with malignant mesothelioma (MM), aged 60 ye ars (range, 46-70 years), with stage 2 disease, in whom the tumor was of sufficient size and accessibility for an intralesional catheter to be inserted. Recombinant human GM-CSF (Molgramostim; Schering Plough) was infused intralesionally for 8 weeks, by using a portable pump, at a dose of 2.5-10 mu g/kg/day. One patient using GM-CSF developed histo logically confirmed necrosis of tumor surrounding the distal catheter, one developed a marked lymphocytic infiltrate in the tumor and had a partial response measured by chest computed tomopraphy (CT) scan, 10 p rogressed, and three had no response. Neutrophilia with morphologic ev idence of neutrophil activation and clinical features suggestive of ne utrophil plugging of blood vessels occurred at doses >5 mu g/kg/day. I n vitro: GM-CSF doubled human neutrophil/CD11b/CD18 expression, sugges ting that neutrophil clumping as seen in vivo might be due to integrin upregulation. Intralesional infusion of cytokines is feasible but can be associated with systemic toxicity and has considerable technical p roblems. It produces a localized immune reaction with tumor regression in a minority of patients.