POLY ICLC AND ALPHA INTERFERON IN REFRACTORY MALIGNANCY

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This trial was designed to test the combination of Poly-ICLC and alpha interferon in patients with refractory malignancy. Alpha interferon induces the synthesis of a number of interferon responsive genes. These induced gene products are responsible for producing the antiproliferative and antiviral effects of alpha interferon are the 2', 5' oligoadenylate synthetase and the P1/EIF2 alpha kinase. Both of these gene products are induced by alpha interferon but require additional factors to activate them. Double- stranded ribonucleic acid is capable of activating both 2', 5' oligoadenylate synthetase and P1/EIF2 alpha kinase. Activation of the latter is associated with potent protein synthesis inhibition. Activation of the latter is associated with potent protein synthesis inhibition. The combination of alpha interferon and double-stranded ribonucleic acids has synergestic antiproliferative effects in several human tumor cell lines including lung, bladder, and sarcomas. The levels of synergism range from 3-250 fold. This study will explore the toxicity, immunologic effects and antitumor activity of the combination of alpha interferon and Poly-ICLC administered by daily subcutaneous and 3 x weekly intramuscular injection, respectively. To date, seventeen patients have been entered on the trial. Two patients were removed from study during the initial week of therapy with alpha interferon alone, one patient due to Grade IV hepatic toxicity and the second patient due to Grade III fatigue. There have been three responses to date, a partial response in a patient with malignant melanoma and two minor responses, one in a patient with renal cell cancer and a second in a patient with rectal carcinoma.