摘要
目的评价卡泊芬净注射剂经验性治疗粒细胞减少伴持续发热患者的安全性、耐受性和疗效。方法本研究为非对照、开放、多中心临床试验,患者因化疗或接受造血干细胞移植出现中性粒细胞绝对值计数<500×106/L,持续至少96h,入选前接受胃肠外广谱抗菌药治疗至少96h,并且在入选前24h内体温>38.0℃者可入选本研究。统计用药人群发生的严重不良事件、不良事件及其总有效率。结果共入选131例,其中安全性分析集(SS)131例,全分析集(FAS)129例。SS131例中,18例受试者发生24例次临床严重不良事件,均与研究药物无关,发生1例次实验室严重不良事件(血钾降低),与研究药物肯定有关。SS131例中发生与药物有关的非严重不良事件者35例,包括5例同时发生临床不良反应和实验室异常;其中16例发生临床不良反应,多见皮疹、发热、呕吐等;24例发生实验室异常,多见ALT等肝酶升高、血钾降低等。总不良反应发生率为26.7%(35/131),其中临床不良反应发生率为12.2%(16/131),实验室异常发生率为19.1%(25/131)。临床不良反应中91.3%为轻、中度。入选病例中9例(12例次)因不良反应而中止治疗,占6.9%(9/131)。其中6例(9例次)被评价为与试验药物有关,发生率为4.6%(6/131)。FAS和符合方案数据集(PPS)中的总体有效率分别为36.4%(47/129)和40.2%(47/117)。结论卡泊芬净经验性治疗粒细胞减少伴持续发热患者临床不良反应多为轻、中度,患者对其耐受性良好,因药物不良反应中止治疗者少见。卡泊芬净用于经验性治疗粒细胞减少伴发热可获一定疗效。
Objective To evaluate the safety, tolerability and efficacy of caspofungin as empirical therapy in patients with persistent fever and neutropenia. Methods This study was an open-label, multicenter, non-comparative clinical trial. The absolute neutrophil count （ANC） of patients was less than 500× 10^6/L for at least 96 hours due to chemotherapy or receiving hematopoietic stem cell transplantation. Patients were treated with parenteral broad-spectrum antimicrobial agents for at least 96 hours prior to enrollment, and those whose temperature was higher than 38.0℃ within 24 hours before enrollment could be included in the study. Descriptive statistics, including serious adverse events （SAE）, adverse events （AE） and overall effective rate of the treated subjects were calculated. Results Of the 131 patients included, there were 131 in the Safety Set （SS） and 129 in the Full Analysis Set （FAS）. A mong SS, 24 episodes of serious adverse events were reported in 18 subjects, which were not considered as drug-related, and one episode of laboratory serious adverse event （decreased serum potassium）, which was considered as definitely drug related. In 35 episodes of drug-related non serious adverse events, the clinical adverse event and laboratory abnormality occurred in 5 subjects concurrently. The clinical adverse reaction was reported in 16 subjects, mainly rash, fever and vomiting; laboratory abnormality was reported in 24 subjects, including increased ALT, increased AST and decreased serum potassium. The incidence of adverse reaction was 26.7%. In the study, 91.3% of the adverse reactions were mild to moderate in severity. Nine （ 12 episodes） subjects discontinued treatment due to adverse events, counting [or 6. 9% （9/131）, among which six subjects （9 episodes） were considered as drug-related. The overall effective rate were 36.4% （47/129） and 40.2% in FAS and per protocol set （PPS）, respectively. Conclusions Both clinical and laboratory adverse effects of caspofungin as empirical therapy in patients with persistent fever and neutropenia were mild and moderate. The drug was well tolerated in this population. The discontinuation due to adverse events is infrequent during the study. Caspofungin is effective when used as empirical therapy in pa tients with persistent fever and neutropenia.
出处
《中国感染与化疗杂志》
CAS
2008年第5期347-354,共8页
Chinese Journal of Infection and Chemotherapy
关键词
卡泊芬净
粒细胞减少伴发热
经验治疗
Caspofungin
Persistent fever and neutropenia
Empirical therapy
