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Thrombopoietic effects and toxicity of interleukin-6 in patients with
ovarian cancer before and after chemotherapy: a multicentric placebo-
controlled, randomized phase Ib study
V D'Hondt, Y Humblet, T Guillaume, S Baatout, C Chatelain, M Berliere, J Longueville, AM Feyens, J de Greve and A Van Oosterom
Department of Oncology, Catholic University of Louvain, Brussels, Belgium.
Recombinant human interleukin-6 (IL-6) has previously been shown to
increase 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 carcinoma.
IL-6 was administered during an initial 7-day cycle before any
chemotherapy. Beginning 7 days later, six cycles of chemotherapy containing
carboplatin were administered every 3 weeks. During chemotherapy cycles 2
to 6, IL-6 was administered from day 4 through day 17 at escalating dose
levels from 0.5 to 10 micrograms/kg/d. At each level, three patients
received IL-6 and one patient received a placebo. During the
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 administration.
Dose-dependent increases in C- reactive protein (CRP) and fibrinogen levels
were observed on day 8 (P < .0001 for both). A significant decrease in
hemoglobin level occured rapidly after initiation of IL-6 therapy and was
maximal on day 8 (P < .001). When given after chemotherapy, IL-6
accelerated platelet recovery after chemotherapy cycles 2 to 6.
Postponements of scheduled chemotherapy due to thrombocytopenia were less
frequent in patients treated with IL-6. No difference in either neutrophils
or peripheral blood progenitor assays was observed during or after IL-6
treatment. Toxicity of IL-6 appeared mild and was not dose-limiting up to
10 micrograms/kg/d. Systemic symptoms such as fever, headache, and myalgia
were the main side effects and were easily relieved by acetaminophen
administration. No biologic toxicity was observed. The data indicate that
IL-6 is a well-tolerated cytokine and capable of accelerating platelet
recovery in patients receiving chemotherapy.
Volume 85,
Issue 9,
pp. 2347-2353,
05/01/1995
Copyright © 1995 by The American Society of Hematology
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