Betts Robert F, Nucci Marcio, Talwar Deepak, Gareca Marcelo, Queiroz-Telles Flavio, Bedimo Roger J, Herbrecht Raoul, Ruiz-Palacios Guillermo, Young Jo-Anne H, Baddley John W, Strohmaier Kim M, Tucker Kimberly A, Taylor Arlene F, Kartsonis Nicholas A
University of Rochester, Rochester, New York, USA.
Clin Infect Dis. 2009 Jun 15;48(12):1676-84. doi: 10.1086/598933.
The standard caspofungin treatment regimen (50 mg/day after a 70-mg dose on day 1) is effective and well tolerated for the treatment of invasive candidiasis, but experience with higher doses of caspofungin is limited. We evaluated the safety and efficacy of caspofungin at 3 times the standard dosing regimen.
Patients with proven invasive candidiasis were randomized to receive a standard or high-dose (150 mg/day) caspofungin treatment regimen. Safety was assessed in all patients as treated. Efficacy was assessed as a secondary objective in a full-analysis-set population. A favorable overall response was defined as symptom resolution and microbiological clearance at the end of caspofungin therapy.
A total of 204 patients were included in the safety analysis (104 received the standard regimen, and 100 received the high-dose regimen), and 197 were included in the efficacy analysis (102 and 95 in the standard and high-dose treatment groups, respectively). Patient demographic characteristics, neutropenia status (6.7% and 8.0% had neutropenia, respectively), and Acute Physiology and Chronic Health Evaluation II scores (mean, 16.5 and 17, respectively) were similar between treatment groups. Significant drug-related adverse events occurred in 1.9% of patients receiving the standard regimen and 3.0% of patients receiving the high-dose regimen (difference, 1.1%; 95% confidence interval, -4.1% to 6.8%). The most-common drug-related adverse events in the standard and high-dose treatment groups were phlebitis (3.8% and 2.0%, respectively), increased alkaline phosphatase level (6.9% and 2.0%, respectively), and increased aspartate transaminase level (4.0% and 2.0%, respectively). Overall, 71.6% of patients who received the standard regimen and 77.9% of patients who received the high-dose regimen had favorable overall responses (difference, 6.3%; 95% confidence interval, -5.9% to 18.4%; not statistically significant). Mortality at 8 weeks after therapy was similar between groups.
Both caspofungin dosing regimens were effective and well tolerated in patients with invasive candidiasis. No safety concerns were found for caspofungin at a dosage of 150 mg/day.
卡泊芬净的标准治疗方案（第1天给予70mg剂量后，每日50mg）治疗侵袭性念珠菌病有效且耐受性良好，但高剂量卡泊芬净的经验有限。我们评估了3倍标准剂量方案的卡泊芬净的安全性和有效性。
确诊为侵袭性念珠菌病的患者被随机分配接受标准或高剂量（每日150mg）卡泊芬净治疗方案。对所有接受治疗的患者进行安全性评估。在全分析集人群中将疗效作为次要目标进行评估。良好的总体反应定义为卡泊芬净治疗结束时症状缓解和微生物清除。
共有204例患者纳入安全性分析（104例接受标准方案，100例接受高剂量方案），197例纳入疗效分析（标准治疗组和高剂量治疗组分别为102例和95例）。治疗组之间患者的人口统计学特征、中性粒细胞减少状态（分别为6.7%和8.0%有中性粒细胞减少）以及急性生理与慢性健康状况评分II（均值分别为16.5和17）相似。接受标准方案的患者中有1.9%发生显著的药物相关不良事件，接受高剂量方案的患者中有3.0%发生（差异为1.1%；95%置信区间为-4.1%至6.8%）。标准治疗组和高剂量治疗组中最常见的药物相关不良事件为静脉炎（分别为3.8%和2.0%）、碱性磷酸酶水平升高（分别为6.9%和2.0%）以及天冬氨酸转氨酶水平升高（分别为4.0%和2.0%）。总体而言，接受标准方案的患者中有71.6%、接受高剂量方案的患者中有77.9%有良好的总体反应（差异为6.3%；95%置信区间为-5.9%至18.4%；无统计学意义）。治疗后8周时两组的死亡率相似。
两种卡泊芬净给药方案对侵袭性念珠菌病患者均有效且耐受性良好。未发现每日150mg剂量的卡泊芬净存在安全性问题。
