P3.02c-093 A Prospective, Randomized, Multicenter, Phase III Study, Comparing rhTPO with rhIL-11 Treating CIT (NCT02344979): Topic: IT Clinical

Abstract

Chemotherapy-induced thrombocytopenia (CIT) is a common dose limiting toxicity of clinical chemotherapy drugs, which may lead to reduced dose chemotherapy or delay chemotherapy time, and even terminate chemotherapy treatment. This is the first randomized, open-label, multicenter, phase III study to compare the efficacy and safety of prophylactic treatment for thrombocytopenia in China. We tried to investigate the efficacy and safety of preventive application with rhTPO or rhIL-11 to protect against CIT in advanced non-small-cell lung cancer (NSCLC) patients. From June 2009 to July 2016, 108 patients with NSCLC who were receiving the first-line platinum-based chemotherapy suffered from severe thrombocytopenia(the nadir of platelet counts＜50×109/L) during the prior chemotherapy cycle. They were randomized to rhTPO arm or rhIL-11 arm in the following chemotherapy cycle, and the chemotherapy regimens and drug doses were consistent with that in the prior and following cycle (GC Gemcitabine 1000-1250 mg/m2, D1 and D8; Carboplatin dosing by AUC value=5, D1; Q3W) or GP (Gemcitabine 1000-1250 mg/m2, D1 and D8; Cisplatin 75 mg/m2, D1; Q3W). 77 patients (56males, 21 females) were enrolled in rhTPO arm and 31 patients (18 males, 13 females) were enrolled in rhIL-11 arm. There were no statistical difference between two arms in terms of gender, age and the nadir of platelet counts during prior chemotherapy cycle(P＞0.05). rhTPO (15000U/d) was injected subcutaneously on the 2nd, 4th, 6th, 9th Day after the initiation of chemotherapy, and IL-11(3mg/d) was injected subcutaneously per day from Day 9 to Day15 after the initiation of chemotherapy. Blood routines were conducted to test before chemotherapy initiation and the 3rd, 5th, 7th, 9th, 11th, 13th, 15th, 17th, and 21st day after chemotherapy. Toxicity and efficacy were monitored. In the following chemotherapy cycle there were no statistical difference between rhTPO arm and rhIL-11 arm on the following indexes: the nadir of platelet counts (62.6±39.4×109/L vs. 52.8±36.8×109/L, P＞0.05), the maximum platelet counts (223.5±127.3×109/L vs. 245.8±158.7×109/L, P＞0.05), duration of platelet counts less than 50×109/L[Median (95%CI): 4.0 (3.0-5.0) days vs. 4.5 (3.0-9.0) days, P＞0.05], time of platelet count recovered to 75×109/L [Median (95% CI): 5(3-7) days vs. 6 (4-8) days, P＞0.05] and to 100×109/L[median (95% CI): 6(6-8) days vs. 6 (5-9) days, P＞0.05]. Drug-related adverse events in rhTPO arm were less than those of rhIL-11 arm (5 cases (6.49%) in rhTPO arm, 8 cases (25.8%) in rhIL-11 arm, P<0.05). Although there is no statistical difference on efficacies, prophylactic administration of rhTPO is safer and more convenient than that of rhIL-11 in advanced NSCLC patients.