Laboratory Correlates of Chemoimmunotherapy with Low-Dose Recombinant Interleukin-2 and Mitomycin C in Patients with Advanced Carcinoma

Abstract

Based on our clinical findings that the ability of cancer patients to generate lymphokine-activated killer (LAK) cells was remarkably augmented after mitomycin C (MMC) administration, we designed a treatment regimen that consisted of MMC 12 mg/m², i.v. on day 1 and recombinant interleukin-2 (IL-2) 700 U/m², i.v. every 12 hr from day 4 through day 8. Of 29 patients with advanced carcinoma treated with this regimen, 10 had a partial response (PR) and 4 had a minor response. The correlation of hematological and immunological changes associated with this treatment with the antitumor response to this therapy was investigated. 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 nonresponder patients. However, there was no correlation between clinical response and cytotoxic activities of peripheral blood mononuclear (PBM) cells, including NK and LAK activity, and the ability to generate LAK cells after the treatment. The capacity of adherent cells in PBM to produce IL-I-β was increased after the treatment in both responders and nonresponders, whereas IL-1-α production was not increased. In addition, a significant increase in the ability to produce TNF-α was observed only in responders, indicating the correlation of TNF-α production with clinical response to this therapy. Since these correlations had been reported in the previous studies using IL-2, the present results suggested that the therapeutic effectiveness of this therapy against advanced carcinoma, is due to IL-2 probably augmented by its combination with MMC. In addition, these parameters might be predictive of therapeutic efficacy of this treatment.