IMMUNOMODULATION OF INTERLEUKIN-2 BY CYCLOPHOSPHAMIDE - A PHASE-IB TRIAL

The objective of this phase IB trail was to determine if cyclophospham ide (CY) could enhance the immune effects of interleukin-2 (IL-2), and if it could, was there an optimal immunomodulatory dosage. IL-2 alone at 30 million IU/m2 thrice weekly for 6 weeks or in combination with varying dosages of CY (300, 600, and 1,200 mg/m2) administered 3 days before IL-2 and repeated 3 weeks later was given to consecutive cohort s of patients (at least five per group) with advanced malignancies of varying types. To gauge the immune effects of the treatment, the varia tion in the amount of lymphokine-activated killer (LAK) cells generate d in the peripheral blood mononuclear cells of patients and in a contr ol group of normal volunteers was measured weekly over 7 consecutive w eeks. Other immune parameters [natural killer cells (NK), peripheral b lood eosinophils and lymphocytes, cell surface markers, soluble IL-2 r eceptor, and IL-2 antibodies] were also closely followed to study if t hey correlated with the degree of LAK activity. The group of patients that received low-dosage CY (300 mg/m2) and IL-2 produced the highest and most sustained levels of LAK and NK activity (p < 0.05) when compa red with the cohorts receiving IL-2 alone or to those receiving the hi gher dosages of CY. No other immune parameter showed a significant dif ference between the groups. Although low-dosage CY does increase the L AK activity seen with IL-2, only randomized clinical trials can determ ine if this enhancement will improve tumor responses.