Kudoh S, Sawa T, Kurihara N, Furuse K, Kurita Y, Fukuoka M, Takada M, Takaku F, Ogawa M, Ariyoshi Y
First Department of Internal Medicine, Osaka City University Medical School, Japan.
Cancer Chemother Pharmacol. 1996;38 Suppl:S89-95. doi: 10.1007/s002800051046.
Recombinant human interleukin 3 (rhIL-3) has been suggested to be a useful agent for the treatment of chemotherapy-induced thrombocytopenia. For evaluation of this possibility, rhIL-3 was given subcutaneously for 10 days to patients with small-cell lung cancer (SCLC). Chemotherapy consisted of carboplatin (CBDCA) given at 400 mg/m2 to previously untreated patients or at 350 mg/m2 to previously treated patients on day 1 and etoposide (VP-16) given at 100 mg/m2 on days 1-3 every 4 weeks. If the platelet count nadir was < 75,000/microliters in the control cycle of chemotherapy, patients were randomly assigned for the next cycle to rhIL-3 given at 5 or 10 micrograms/kg per day on days 4-13. A total of 41 patients (32 previously untreated patients and 9 previously treated patients) were enrolled in the study. The platelet count nadir in the cycles including rhIL-3 was significantly higher at both dose levels (P < 0.01) than in the control cycle. The duration of thrombocytopenia (< 75,000/microliters) and the mean time from the 1st day of chemotherapy to thrombocyte recovery (> 100,000/microliters) in the rhIL-3 cycle were significantly shorter than those in the control cycle (P < 0.01). The neutrophil count nadir and the duration of neutropenia (<1,000/microliters) were also significantly improved in the rhIL-3 cycle (P < 0.05). The major side effects were fever (80.5%), headache (24.3%), and fatigue (14.6%). All side effects were tolerable and of less than grade II. There was no difference in the efficacy of the two dose levels, but the 5-micrograms/kg dose appeared to be better tolerated than the 10-micrograms/ kg dose. We conclude that rhIL-3 administration following chemotherapy consisting of CBDCA and VP-16 reduces the incidence and severity of chemotherapy-induced thrombocytopenia and neutropenia with an acceptable adverse-events profile.
重组人白细胞介素3（rhIL-3）已被认为是治疗化疗引起的血小板减少症的有效药物。为评估这种可能性，对小细胞肺癌（SCLC）患者皮下注射rhIL-3，持续10天。化疗方案为：初治患者第1天给予卡铂（CBDCA）400mg/m²，复治患者给予350mg/m²，依托泊苷（VP-16）在第1 - 3天给予100mg/m²，每4周重复一次。如果化疗对照周期中血小板计数最低点<75,000/微升，患者在下一周期随机分配接受rhIL-3治疗，剂量为5或10微克/千克，于第4 - 13天每天给药。共有41例患者（32例初治患者和9例复治患者）纳入研究。在包含rhIL-3的周期中，两个剂量水平的血小板计数最低点均显著高于对照周期（P < 0.01）。rhIL-3周期中血小板减少症（<75,000/微升）的持续时间以及从化疗第1天到血小板恢复（>100,000/微升）的平均时间均显著短于对照周期（P < 0.01）。rhIL-3周期中中性粒细胞计数最低点和中性粒细胞减少症（<1,000/微升）的持续时间也显著改善（P < 0.05）。主要副作用为发热（80.5%）、头痛（24.3%）和疲劳（14.6%）。所有副作用均可耐受，且均低于II级。两个剂量水平的疗效无差异，但5微克/千克剂量似乎比10微克/千克剂量耐受性更好。我们得出结论，在由CBDCA和VP-16组成的化疗后给予rhIL-3可降低化疗引起的血小板减少症和中性粒细胞减少症的发生率及严重程度，且不良事件情况可接受。
