Immunotherapy with IL2 by constant infusion and weekly doxorubicin

Twelve women and 7 men, median age 58 (range 17-74), with a diagnosis of non-small-cell lung cancer (11 patients), inflammatory breast cancer (5 patients), osteosarcoma (2 patients), and colon carcinoma (1 patient) were studied. Treatment consisted of four consecutive 6-day courses of infusional interleukin-2 (IL2); 9 patients were treated with 20 X 10(6) IU/m2/day and 10 patients received weekly dose increments of 50% until the maximally tolerated dose was reached. One day after each course was completed patients received doxorubicin, 30 mg/m2; infusional IL2 was resumed 24 h after receiving doxorubicin. Rebounds of lymphocytes with high spontaneous synthetic rates of DNA occurred one day after stopping the infusion, despite doxorubicin administration. The kinetics were not different from earlier trials using IL2 alone. Sequential lymphocyte analysis showed that helper (CD4) and suppressor (CD8) T-cell subsets increased after the first week of treatment and declined thereafter, whereas the proliferation of natural killer (NK) cells (CD16) progressed through the 4-week treatment unaffected by doxorubicin. Mean cytolytic ability induced by IL2 against NK-resistant tumors in vitro was higher in patients who had evidence of clinical tumor regression and therefore is prognostically valuable (p = .02). Three patients left the study prematurely. Five partial remissions and 2 minimal responses were seen in the remaining 16 patients, but they were short-lived. Of the responding patients, only one had failed prior doxorubicin-containing chemotherapy. Toxicities attributable to IL2 and doxorubicin were encountered, and were manageable at these doses. Our data suggest that doxorubicin did not have cytotoxic or suppressive effects on lymphokine-induced lymphocyte functions and that both treatment modalities in combination are worthy of further investigation since they exert distinct and compatible cytotoxic mechanisms and induced tumor regressions with acceptable toxicity in a group of patients with poorly responsive cancers.