HIGH DOSE-INTENSE CHEMOTHERAPY ALONE OR IN COMBINATION WITH INTERLEUKIN-2 FOR SMALL-CELL LUNG-CANCER - A PILOT-STUDY

Given the antitumor activity of interleukin-2 (IL-2) against some drug -resistant cancer cells, 17 previously untreated patients with small c ell lung cancer entered a pilot study to evaluate the feasibility, eff icacy, and immunological effects of combining 12-week high dose-intens e chemotherapy based on a modified Evans regimen (CAV/PE) with differe nt IL-2 schedules (6-12 MU/m(2) week as a 48-72-h infusion using the s ame cumulative dose, 72 MU/m(2)). Despite significant myelotoxicity, u p to 70% of the intended dose intensity was delivered, showing no diff erences with regard to the IL-2 schedule used. Immunotherapy-induced t oxicity was usually mild and manageable. No limiting effects were obse rved in patients receiving immunotherapy except for a very poor compli ance to the 12-week IL-2 regimen. The low-dose 72-h infusion was the o ptimal IL-2 schedule. As given in this study, neither of the alternati ng CAV/PE regimens abrogated the effects of IL-2 on T-cell and NK-cell subsets, showing typical kinetics with rebound in lymphocytes followi ng each discontinuation of the IL-2. While immunological changes canno t predict the antitumor effect of IL-2, they are consistent with those described for IL-2 alone, suggesting its compatibility with high dose -intense chemotherapy. Although no definite advantages have been demon strated in this small pilot study with significant unbalanced prognost ic factors (12% 2-year survival), both the preserved immunostimulatory effects and the lack of limiting overlapping toxicity make this combi ned approach promising and worthy of further clinical investigation.