FLAVONE ACETIC-ACID (FAA) WITH RECOMBINANT INTERLEUKIN-2 (RIL-2) IN ADVANCED MALIGNANT MELANOMA-III - CYTOKINE STUDIES

Twelve patients undergoing IL-2 and flavone acetic acid (FAA) combinat ion immunotherapy for advanced melanoma were studied throughout treatm ent for the induction of measurable levels of bioactive TNF, GM-CSF an d IL-6 in their serum. This was to assess the extent of secondary cyto kine induction in these patients and the possible role of such cytokin es in both the toxic and therapeutic responses. The nature of the trea tment schedule enabled these cytokines to be measured in response to F AA alone, FAA/IL-2 and FAA alone following IL-2/FAA activation of targ et cells. A small rise in the serum levels of these cytokines was seen on the initial course of FAA/IL-2 but this was minor compared to the marked elevation in levels 2-8 h following the initiation of the third course of FAA given with or without IL-2 and at a time point which co incided with maximum toxicity in those patients who experienced it. Th ese results show that FAA alone can induce cytokine release from prime d target cells. This may be associated with the therapeutic effect and /or toxicity of the agent.