THE PROGNOSTIC-SIGNIFICANCE OF IMMUNE CHANGES IN PATIENTS WITH RENAL-CANCER, MELANOMA AND COLORECTAL-CANCER, TREATED WITH INTERFERON-ALPHA-2B

In the present study we evaluated the response rate and tile immunores torative proper ties of interferon alpha 2b (IFn alpha 2b) administere d to patients with advanced renal cell cat-cinema (RCC), melanoma (MEL ) or colorectal cancer (CC). We studied the immune status and correlat ed it with clinical responses. Thirty-five patients with advanced RCC, and 14 with MEL were treated with recombinant INF alpha 2b. The dose was increased progressively from 5 x 10(6) IU/day in the first week (t hree times every week) to 10 x 10(6) IU/day in the second week and the reafter to 15 x 10(6) IU/day subcutaneously. In patients with CC INF a lpha 2b was given at 5 x 10(6) IU/day every other day (three times eve ry week); these patients also received (together with INF) leucovorin 200 mg m(-2) day(-1) in a 1-h i.v. infusion every week, and mid-infusi on 400 mg/m(2) 5-FU was administered as an intravenous bolus every wee k. The response rate was as follows: for RCC, 6 patients achieved part ial response (PR). 10 stable disease (SD), and 21 progressed (PD; or M EL, 5 patients achieved PR and 9 PD; for CC, 6 achieved PR, 5 SD, and 9 PD. In all patients blood was withdrawn prior to INF alpha 2b treatm ent and then monthly. T lymphocytes, after isolation from peripheral b lood, were tested for proliferation in the autologous mixed-lymphocyte reaction and allogeneic mixed-lymphocyte reaction, interleukin-2 (IL- 2) production, expression of IL-2 receptors during the allogeneic-mixe d-lymphocyte reaction, and the production of IL-1 by peripheral blood monocytes. Striking increases were demonstrated in all parameters 2 mo nths after treatment with INF alpha 2b. In comparison to normal contro ls, all patients, with tile malignant neoplasms presented decreased (> 45%) mean values of the immunological parameters under investigation ( P 0.0001). Responders (patients with RCC, MEL, and PR) presented lower mean values of all the parameters studied than did non-responders (P 0.0001). Patients with CC presented the lowest mean values of the para meters than did the other patients (RCC, MEL) !P 0.0001). After therap y with INF alpha 2b, patients with RCC experiencing PR showed a mean i ncrease of more than 30% (P 0.0001). Patients with SD showed a mean in crease of about 20% (P 0.0001), and those with PD showed a 6% increase in the immunological parameters under investigation. Patients with ME L experiencing PR showed a mean increase of more than 30% and patients with PD a decrease of mole than 10% (P 0.0001), All patients, regardl ess of the clinical response, achieved an increase of more than 60% (P 0.0001). Administration of IFN alpha 2b resulted in a marked potentia tion of a deficient cellular immune response in vitro in those patient s with RCC and MEL whet responded to the treatment. On the other hand, non-responders. demonstrated a decrease in the examined parameters an d, in some, deterioration of the already depressed immunological funct ions was observed. This observation can have prognostic significance r egarding clinical response of INF. In contrast, our findings show that the immune stimulation associated with INF alpha treatment in all our CC patients did not predict an improved clinical outcome, There are s everal theoretical explanations for this discrepancy.