LABORATORY CORRELATES OF CHEMOIMMUNOTHERAPY WITH LOW-DOSE RECOMBINANTINTERLEUKIN-2 AND MITOMYCIN-C IN PATIENTS WITH ADVANCED-CARCINOMA

Based on our clinical findings that the ability of cancer patients to generate lymphokine-activated killer (LAK) cells was remarkably augmen ted after mitomycin C (MMC) administration, we designed a treatment re gimen that consisted of MMC 12 mg/m(2), i.v. on day 1 and recombinant interleukin-2 (IL-2) 700 U/m(2), i.v. every 12 hr from day 4 through d ay 8. Of 29 patients with advanced carcinoma treated with this regimen , 10 had a partial response (PR) and 4 had a minor response. The corre lation of hematological and immunological changes associated with this treatment with the antitumor response to this therapy was investigate d. Pretreatment values of total white blood cell and lymphocyte counts , and the level of increase of eosinophil counts in responder patients who showed a PR, were significantly greater than those in nonresponde r patients. However, there was no correlation between een clinical res ponse and cytotoxic activities of peripheral blood mononuclear (PBM) c ells, including NK and LAK activity, and the ability to generate LAK c ells after the treatment. The capacity of adherent cells in PBM to pro duce IL-1-beta was increased after the treatment in both responders an d nonresponders, whereas IL-1-alpha production was not increased. In a ddition, a significant increase in the ability to produce TNF-alpha wa s observed only in responders, indicating the correlation of TNF-alpha production with clinical response to this therapy. Since these correl ations had been reported in the previous studies using IL-2, the prese nt results suggested that the therapeutic effectiveness of this therap y against advanced carcinoma, is due to IL-2 probably augmented by its combination with MMC. In addition, these parameters might be predicti ve of therapeutic efficacy of this treatment.