COMBINED IMMUNOTHERAPY USING INTERFERON-α, INTERLEUKIN-2 AND LYMPHOKINE-ACTIVATED KILLER CELLS

Improvement of Quality of Life in Patients with Advanced Renal Cell Carcinoma

Abstract

The goal of any treatment strategy for cancer is to improve not only patient survival but also quality of that survival. Between March 1990 and February 1993, we treated 10 patients with advanced RCC (9 men and 1 women) by combined immunotherapy using natural interferon-α (IFN-α), recombinant interleukin-2 (rIL-2) and lymphokine-activated killer (LAK) cells, and resulting the quality of life (QOL) issues examined. The ages of the patients ranged from 36 to 78 years (mean: 60.2) and the performance status (PS) ranged from 30 to 100% (mean: 77%). There were 8 lung, 3 bone, 2 brain and 1 neck and para-aortic lymph node metastases. We could evaluate 8 patients, 2 patients dropped out because of bone fracture and acute pneumonia. The protocol was as follows; 1×10⁶IU of rIL-2 as an intravenous infusion and 6×10⁶IU of IFN-α intramuscularly on days 1-7 and 15-21. In additions LAK cells obtained from the patients were given on days 14, 21, 28, and 35 intravenously. This protocol was repeated for more than three cycles (mean: 4.13 cycles) in each patient. The maintenance therapy on outpatient basis were performed in 4 patients after confirmation of the safety of the combined immunotherapy. This outpatient regimen was composed of 1×10⁶IU of rIL-2 intravenously, 6×10⁶IU of IFN-α intramuscularly on days, 1, 8, 15, 22, and 29, plus LAK cells on days 15 and 29. We repeated this protocol for 3-5 cycles (mean: 4.25 cycles). PS were 78.8±8.61% (mean±S. E.) when the patients entered into this study. After one month, PS increased to 92.5±4.12% (p=0.054) and after three months, to 90.0±4.23% (p=0.122). The mean survivsal period was 18 months. PS were improved remarkably from 30% to 80% in the patient who had cervival vertebrae metastasis. PS was maintained in 3 patients of 4, over 3 months by the maintenance therapy. The side effects were fever (75%), anemia (50%), granulocytopenia (25%), and gastrointestinal toxicity (12.5%), but no toxicities were more than grade II according to WHO classification. No toxicity worse than WHO gradel I was observed in the maintenance therapy, therefore this outpatient regimen was completed safely in all four patients. The response rate was 25% (2 PR, 1 NC and 5 PD) by this combined immunotherapy. These findings suggested that this combined immunotherapy regimen was the alternative strategy in order to improve QOL in the patients with advanced RCC.