Malik I A, Moid I, Aziz Z, Khan S, Suleman M
Department of Medical Oncology, National Cancer Institute, Karachi, Pakistan.
Am J Med. 1998 Dec;105(6):478-83. doi: 10.1016/s0002-9343(98)00326-x.
Several studies have documented the efficacy of amphotericin B as empiric antifungal therapy in cancer patients with prolonged fever and neutropenia. Amphotericin, however, is a toxic drug. Fluconazole has broad-spectrum antifungal activity with an excellent safety profile. Although prophylactic use of fluconazole is widespread, its efficacy as an empiric antifungal agent has not been extensively investigated.
We randomly assigned 106 patients with absolute neutropenia (< or = 500 cells microL) and persistent fever of undetermined origin (> 38 degrees C) despite 1 week of broad-spectrum antibiotic therapy to receive either fluconazole 400 mg orally daily or amphotericin B 0.5 mg/kg/day. Patients with obvious invasive fungal infections were excluded, as were those with abnormal renal or hepatic function. Success was defined as defervescence with the initially assigned antifungal regimen without development of clinically evident invasive fungal infection.
Six patients were excluded from the analysis, mostly because they did not have severe neutropenia. Forty-eight patients received amphotericin B, and 52 received fluconazole. Baseline clinical characteristics and laboratory parameters as well as duration of neutropenia (7.7 versus 6.9 days), duration of fever (7.8 versus 8.1 days), and duration of hospitalization (10.4 versus 8.3 days) were similar between those receiving amphotericin and fluconazole. Treatment success rates and mortality rates were similar in the two groups: 22 (46%) patients in the amphotericin group and 29 (56%) patients in the fluconazole group responded successfully to therapy (P = 0.3), whereas 16 (33%) patients in the amphotericin group and 14 (27%) patients in the fluconazole group died during hospitalization (P = 0.5). Adverse events such as chills and fever (4 versus 1), bronchospasm (2 versus none), severe hypokalemia (25 versus 12) and nephrotoxicity (9 versus 3) were more frequently observed in patients receiving amphotericin. Adverse prognostic factors included prolonged duration of neutropenia and pneumonia.
These results suggest that fluconazole is an equally effective but less toxic alternative to amphotericin B as empiric antifungal therapy in cancer patients with prolonged fever and neutropenia.
多项研究已证明两性霉素B作为经验性抗真菌治疗药物，对长期发热且中性粒细胞减少的癌症患者有效。然而，两性霉素是一种有毒药物。氟康唑具有广谱抗真菌活性，安全性良好。尽管氟康唑的预防性使用很普遍，但其作为经验性抗真菌药物的疗效尚未得到广泛研究。
我们将106例绝对中性粒细胞减少（≤500个/微升）且尽管接受了1周广谱抗生素治疗仍持续不明原因发热（>38℃）的患者随机分为两组，一组每天口服400毫克氟康唑，另一组每天接受0.5毫克/千克的两性霉素B治疗。排除有明显侵袭性真菌感染的患者以及肾功能或肝功能异常的患者。成功定义为采用最初分配的抗真菌方案后体温下降，且未发生临床明显的侵袭性真菌感染。
6例患者被排除在分析之外，主要原因是他们没有严重的中性粒细胞减少。48例患者接受两性霉素B治疗，52例患者接受氟康唑治疗。接受两性霉素和氟康唑治疗的患者在基线临床特征、实验室参数以及中性粒细胞减少持续时间（7.7天对6.9天）、发热持续时间（7.8天对8.1天）和住院时间（10.4天对8.3天）方面相似。两组的治疗成功率和死亡率相似：两性霉素组22例（46%）患者、氟康唑组29例（56%）患者治疗成功（P = 0.3），而两性霉素组16例（33%）患者、氟康唑组14例（27%）患者在住院期间死亡（P = 0.5）。接受两性霉素治疗的患者更常出现寒战和发热（4例对1例）、支气管痉挛（2例对无）、严重低钾血症（25例对12例）和肾毒性（9例对3例）等不良事件。不良预后因素包括中性粒细胞减少持续时间延长和肺炎。
这些结果表明，在长期发热且中性粒细胞减少的癌症患者中，作为经验性抗真菌治疗药物，氟康唑是两性霉素B的一种同样有效但毒性较小的替代药物。
