Possible biological indicators of the response to recombinant tumour necrosis factor alpha in patients with advanced...

Tumour Necrosis Factor alpha (TNF alpha) immunotherapy, in addition to that of Interleukin-2 immunotherapy, represents one of the most promising biotherapies for human neoplasms. In order to identify immunological parameters of prognostic value we studied changes in immune response during first cycle of treatment with hree TNF alpha. The study included 21 locally advanced or metastatic solid tumor patients (M/F:12/9 median age: 57 years, range 38-65) for whom no other standard therapy was available. TNF alpha was administered before midday by a 20-minute intravenous infusion at a dose of 75 microg/day for 5 consecutive days corresponding to one cycle. In the absence of progression two further cycles of TNF alpha were given at 14 day intervals during which the dose was increased by 50 microg/day i.e. 2nd cycle- 100 microg/day, 3rd cycle- 150 microg/day. Of 21 patients evaluated for both clinical and immunological responses, 4 had complete response and 4 patients had partial response. The present study suggests that TNF alpha biotherapy is not associated with an increase in the number of circulating lymphocytes. Regarding lymphocyte subtype, a slight increase has been observed as far as T lymphocyte subsets are concerned. The CD4/CD8 ratio in cancer patients treated with hree TNF alpha showed significantly lower values than before treatment. On the basis of in vitro experiments an increase in NK cell activation in tissue culture, in addition to an increase of LAK cells, was observed.