A phase II double-blind randomized study of the simultaneous administration of recombinant human interleukin-6 and recombinant human granulocyte colony-stimulating factor following paclitaxel and carboplatin chemotherapy in patients with advanced epithelial ovarian cancer

Purpose. Recombinant human interleukin-6 (rhuIL-6) is a glycosylated cytoki ne with hematopoietic stimulatory effects. In particular, preclinical studi es suggest the agent can stimulate thrombopoiesis, even in conjunction with chemotherapy. We attempted to determine whether higher dose chemotherapy f or ovarian cancer was possible given the pharmacologic use of this importan t growth factor. Methods. We conducted a randomized, double-blind phase II study of IL-6 plu s granulocyte colony-stimulating factor (G-CSF) versus placebo plus G-CSF i n combination with a standard chemotherapy regimen. Patients with epithelia l ovarian cancer, stages Ic to IV, were eligible. All patients were previou sly untreated with chemotherapy and had Karnofsky performance status greate r than or equal to 60. rhuIL-B (Escherichia coli, SDZ ILS 969) 1.0 mu g/kg or placebo was given subcutaneously on days 2-8 every cycle together with G -CSF 5.0 mu g/kg subcutaneously days 2-15, following administration of pacl itaxel 175 mg/m(2) as a 3-h infusion and carboplatin given to a desired AUC of 7.5 on day 1 every 21 days. Results. Fifty patients were entered in this study, although the study was temporarily suspended by the FDA in midstudy over manufacturing concerns. T herefore, 37 patients were evaluable for efficacy of growth factor; 19 pati ents received placebo plus G-CSF and 18 rhIL-6 plus G-CSF, There was no dif ference in prognostic variables between these two groups. Platelet nadirs w ere lower in the first cycle for the placebo group (P = 0.004, Wilcoxon sum -rank test) but not in other cycles. There was no statistically significant difference in cycle treatment delays, carboplatin dose delivered, number o f patients with grade 4 thrombocytopenia, or platelet transfusion. Nonethel ess, the trend of the data favored IL-6 in all cases. Conclusions. This study demonstrated a minimal effect (statistically signif icant in the first cycle only) on thrombopoiesis in women undergoing paclit axel and carboplatin therapy of ovarian cancer. No clinically significant e ffect on actual chemotherapy delivery was demonstrated, however, Future stu dies, if warranted, to ameliorate thrombocytopenia should be carried out wi th regimens producing even greater thrombocytopenia than the current regime n in the control arm. (C) 1999 Academic Press.