Safrin S, Finkelstein D M, Feinberg J, Frame P, Simpson G, Wu A, Cheung T, Soeiro R, Hojczyk P, Black J R
San Francisco General Hospital, San Francisco, CA 94110.
Ann Intern Med. 1996 May 1;124(9):792-802. doi: 10.7326/0003-4819-124-9-199605010-00003.
To compare the tolerability and efficacy of three oral regimens for the treatment of patients with the acquired immunodeficiency syndrome (AIDS) and Pneumocystis carinii pneumonia.
A randomized, double-blind study.
24 U.S. academic medical centers.
181 patients with morphologically confirmed P. carinii pneumonia and alveolar-arterial oxygen differences (PAO2-PaO2) of 45 mm Hg or less.
Patients were randomly assigned to receive trimethoprim-sulfamethoxazole, dapsone-trimethoprim, or clindamycin-primaquine for 21 days. Patients with a PAO2-PaO2 of 35 to 45 mm Hg at study entry also received prednisone.
Serial clinical and laboratory evaluations for therapeutic response and toxicity. Therapeutic failure at day 21 was defined by any of the following: increase in PAO2-PaO2 of greater than 20 mm Hg; no remission of baseline signs and symptoms; and change in antipneumocystis therapy for reasons other than toxicity, intubation, or death. Dose-limiting toxicity was defined as discontinuation of therapy by the primary physician because of one or more adverse reactions.
No statistically significant differences were seen among treatment groups in the proportions of patients who had dose-limiting toxicity (P=0.2), therapeutic failure (P>0.2), or a complete course of therapy (P>0.2). Survival during therapy or for 2 months thereafter did not differ among the three groups (P>.02). However, elevation of serum aminotransferase levels to more than five times the baseline levels was more frequent in the trimethoprim-sulfamethoxazole group (P=0.003), and one or more serious hematologic toxicities (neutropenia, anemia, thrombocytopenia, or methemoglobinemia) occurred more frequently in the clindamycin-primaquine group (P=0.01).
The rates of dose-limiting toxicity, therapeutic failure, and survival did not differ among patients with AIDS who were receiving oral trimethoprim-sulfamethoxazole, dapsone-trimethoprim, or clindamycin-primaquine for mild to moderate P. carinii pneumonia. However, the limited sample size prevents the unequivocal demonstration of the equality of these three regimens. Differences in expected categories of toxicities associated with each regimen should guide the clinician in choosing first-line therapy, particularly for patients with baseline hepatic insufficiency or myelosuppression.
比较三种口服治疗方案对获得性免疫缺陷综合征（AIDS）合并卡氏肺孢子虫肺炎患者的耐受性和疗效。
一项随机、双盲研究。
美国24家学术医疗中心。
181例经形态学确诊为卡氏肺孢子虫肺炎且肺泡-动脉血氧分压差（PAO2-PaO2）≤45mmHg的患者。
患者被随机分配接受甲氧苄啶-磺胺甲恶唑、氨苯砜-甲氧苄啶或克林霉素-伯氨喹治疗21天。研究开始时PAO2-PaO2为35至45mmHg的患者还接受泼尼松治疗。
对治疗反应和毒性进行系列临床和实验室评估。第21天的治疗失败定义为以下任何一种情况：PAO2-PaO2升高超过20mmHg；基线体征和症状未缓解；因毒性、插管或死亡以外的原因改变抗肺孢子虫治疗方案。剂量限制性毒性定义为主治医生因一种或多种不良反应而停止治疗。
各治疗组在出现剂量限制性毒性（P=0.2）、治疗失败（P>0.2）或完成整个疗程（P>0.2）的患者比例方面无统计学显著差异。三组在治疗期间或之后2个月的生存率无差异（P>.02）。然而，甲氧苄啶-磺胺甲恶唑组血清转氨酶水平升高至基线水平五倍以上的情况更为常见（P=0.003），克林霉素-伯氨喹组出现一种或多种严重血液学毒性（中性粒细胞减少、贫血、血小板减少或高铁血红蛋白血症）的情况更为频繁（P=0.01）。
接受口服甲氧苄啶-磺胺甲恶唑、氨苯砜-甲氧苄啶或克林霉素-伯氨喹治疗轻度至中度卡氏肺孢子虫肺炎的AIDS患者，在剂量限制性毒性、治疗失败率和生存率方面无差异。然而，样本量有限妨碍了明确证明这三种方案的等效性。与每种方案相关的预期毒性类别差异应指导临床医生选择一线治疗方案，特别是对于有基线肝功能不全或骨髓抑制的患者。
