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 the immunorestorative properties of interferon alpha 2b (IFn alpha 2b) administered to patients with advanced renal cell carcinoma (RCC), melanoma (MEL) or colorectal cancer (CC). We studied the immune status and correlated 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 (three times every week) to 10 x 10(6) IU/day in the second week and thereafter to 15 x 10(6) IU/day subcutaneously. In patients with CC INF alpha 2b was given at 5 x 10(6) IU/day every other day (three times every 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-infusion 400 mg/m2 5-FU was administered as an intravenous bolus every week. The response rate was as follows: for RCC, 6 patients achieved partial response (PR), 10 stable disease (SD), and 21 progressed (PD); for MEL, 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 In all patients blood was withdrawn prior to INF alpha 2b treatment and then monthly. T lymphocytes, after isolation from peripheral blood, 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-mixed-lymphocyte reaction, and the production of IL-1 by peripheral blood monocytes. Striking increases were demonstrated in all parameters 2 months after treatment with INF alpha 2b. In comparison to normal controls, all patients with the 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 parameters than did the other patients (RCC, MEL) (P 0.0001). After therapy with INF alpha 2b, patients with RCC experiencing PR showed a mean increase of more than 30% (P 0.0001). Patients with SD showed a mean increase of about 20% (P 0.0001), and those with PD showed a 6% increase in the immunological parameters under investigation. Patients with MEL experiencing PR showed a mean increase of more than 30% and patients with PD a decrease of more than 10% (P 0.0001). All patients, regardless of the clinical response, achieved an increase of more than 60% (P 0.0001). Administration of IFN alpha 2b resulted in a marked potentiation of a deficient cellular immune response in vitro in those patients with RCC and MEL who responded to the treatment. On the other hand, non-responders demonstrated a decrease in the examined parameters and, in some, deterioration of the already depressed immunological functions was observed. This observation can have prognostic significance regarding 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 several theoretical explanations for this discrepancy.
Tsavaris
N
N
Department of Pathological Physiology, University of Athens, School of Medicine, Laiko General Hospital, Greece.
Baxevanis
C
C
Kosmidis
P
P
Papamichael
M
M
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000276:immunology* / Q000628:therapy*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000276:immunology*; D005069:Evaluation Studies as Topic; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000276:immunology* / Q000628:therapy*; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000628:therapy*; D008875:Middle Aged; D011379:Prognosis; D011994:Recombinant Proteins
D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins