THROMBOPOIETIC EFFECTS AND TOXICITY OF INTERLEUKIN-6 IN PATIENTS WITHOVARIAN-CANCER BEFORE AND AFTER CHEMOTHERAPY - A MULTICENTRIC PLACEBO-CONTROLLED, RANDOMIZED PHASE IB STUDY

Recombinant human interleukin-6 (IL-6) has previously been shown to in crease platelet counts in normal and sublethally irradiated mice, dogs , and primates. To assess its tolerance and efficacy in clinical use, we performed a randomized phase Ib study in patients with ovarian carc inoma. IL-6 was administered during an initial 7-day cycle before any chemotherapy. Beginning 7 days later, six cycles of chemotherapy conta ining carboplatin were administered every 3 weeks. During chemotherapy cycles 2 to 6, IL-6 was administered from day 4 through day 17 at esc alating dose levels from 0.5 to 10 mu g/kg/d. At each dose level, thre e patients received IL-6 and one patient received a placebo. During th e prechemotherapy cycle of IL-6, a dose-dependent increase in platelet count was observed from day 12 to 15 and was maximal on day 15 (r = . 77; P < .01). The median ploidy of bone marrow megakaryocytes shifted from 16 N to 32 N after 7 days of the initial prechemotherapy IL-6 adm inistration. Dose-dependent increases in C-reactive protein (CRP) and fibrinogen levels were observed on day 8 (P < .0001 for both). A signi ficant decrease in hemoglobin level occured rapidly after initiation o f IL-6 therapy and was maximal on day 8 (P < .001). When given after c hemotherapy, IL-6 accelerated platelet recovery after chemotherapy cyc les 2 to 6. Postponements of scheduled chemotherapy due to thrombocyto penia were less frequent in patients treated with IL-6. No difference in either neutrophils or peripheral blood progenitor assays was observ ed during or after IL-6 treatment. Toxicity of IL-6 appeared mild and was not dose-limiting up to 10 mu g/kg/d. Systemic symptoms such as fe ver, headache, and myalgia were the main side effects and were easily relieved by acetaminophen administration. No biologic toxicity was obs erved. The data indicate that IL-6 is a well-tolerated cytokine and ca pable of accelerating platelet recovery in patients receiving chemothe rapy. (C) 1995 by The American Society of Hematology.