Smith J W, Longo D L, Alvord W G, Janik J E, Sharfman W H, Gause B L, Curti B D, Creekmore S P, Holmlund J T, Fenton R G
Biological Response Modifiers Program, Frederick Cancer Research and Development Center, National Cancer Institute, Md.
N Engl J Med. 1993 Mar 18;328(11):756-61. doi: 10.1056/NEJM199303183281103.
Thrombocytopenia is a frequent side effect of cancer chemotherapy and commonly limits attempts to escalate drug doses. To determine whether interleukin-1 alpha could ameliorate carboplatin-induced thrombocytopenia, we combined it with high-dose carboplatin in 43 patients with advanced neoplasms.
High-dose carboplatin (800 mg per square meter of body-surface area) was administered alone to a control group. Subsequent patients were randomly assigned to receive the same dose of carboplatin with interleukin-1 alpha, administered either before or after carboplatin. Interleukin-1 alpha was given intravenously at a dose of 0.03, 0.1, or 0.3 microgram per kilogram of body weight per day for five days.
Carboplatin alone consistently produced thrombocytopenia with a median nadir of 19,000 platelets per cubic millimeter and a median of 10 days with less than 100,000 platelets per cubic millimeter. All 15 patients receiving interleukin-1 alpha before carboplatin had similar findings. In contrast, 5 of the 15 patients given one of the two higher doses of interleukin-1 alpha after carboplatin had minimal thrombocytopenia (nadir, 91,000 to 332,000 platelets per cubic millimeter). In the 10 patients given 0.3 microgram of interleukin-1 alpha per kilogram after carboplatin treatment, the platelet count recovered to 100,000 per cubic millimeter significantly earlier than in either the control group (P = 0.002) or the patients who received interleukin-1 alpha before carboplatin (P = 0.003), with the median times to recovery in the three groups being 16, 21, and 23 days, respectively. At the highest dose of interleukin-1 alpha, toxicity was substantial (but reversible), requiring inpatient support for hypotension, supraventricular arrhythmias, and pulmonary-capillary leak.
Interleukin-1 alpha can accelerate the recovery of platelets after high-dose carboplatin therapy and may be clinically useful in preventing or treating thrombocytopenia induced by chemotherapy.
血小板减少是癌症化疗常见的副作用，通常会限制提高药物剂量的尝试。为了确定白细胞介素-1α是否能改善卡铂引起的血小板减少，我们将其与高剂量卡铂联合用于43例晚期肿瘤患者。
对照组单独给予高剂量卡铂（每平方米体表面积800毫克）。随后的患者被随机分配接受相同剂量的卡铂并联合白细胞介素-1α，白细胞介素-1α在卡铂之前或之后给药。白细胞介素-1α以每天每千克体重0.03、0.1或0.3微克的剂量静脉注射，共5天。
单独使用卡铂持续导致血小板减少，最低点中位数为每立方毫米19,000个血小板，中位数为10天血小板计数低于每立方毫米100,000个。所有15例在卡铂之前接受白细胞介素-1α的患者有相似的结果。相比之下，15例在卡铂之后接受两种较高剂量白细胞介素-1α之一的患者中有5例血小板减少轻微（最低点，每立方毫米91,000至332,000个血小板）。在卡铂治疗后给予每千克0.3微克白细胞介素-1α的10例患者中，血小板计数恢复到每立方毫米100,000个明显早于对照组（P = 0.002）或在卡铂之前接受白细胞介素-1α的患者（P = 0.003），三组恢复的中位时间分别为16、21和23天。在白细胞介素-1α的最高剂量时，毒性很大（但可逆），需要住院治疗低血压、室上性心律失常和肺毛细血管渗漏。
白细胞介素-1α可加速高剂量卡铂治疗后血小板的恢复，在预防或治疗化疗引起的血小板减少方面可能具有临床应用价值。
