Tohda Y, Iwanaga T, Takada M, Yana T, Kawahara M, Negoro S, Okishio K, Kudoh S, Fukuoka M, Furuse K
Fourth Department of Internal Medicine, Kinki University, Osaka, Japan.
Chemotherapy. 1999 May-Jun;45(3):197-204. doi: 10.1159/000007183.
To determine the efficacy, toxicity and pharmacokinetics of intrapleural cisplatin (CDDP) and etoposide as a treatment for malignant pleural effusions (MPE) in patients with non-small cell lung cancer (NSCLC).
Seventy patients with MPE associated with NSCLC were enrolled in this study. In 68 patients, a catheter was inserted into the pleural cavity, within 24 h after complete drainage of the pleural effusion, CDDP (80 mg/m2) and etoposide (80 mg/m2) were simultaneously administered successfully via the catheter and the catheter was clamped. Seventy-two hours later, the catheter was unclamped to allow drainage. The catheter was removed when the accumulated intrapleural fluid decreased to 20 ml or less per day.
The pharmacokinetic profiles showed high maximum concentrations of CDDP (free form, 88 microg/ml) and etoposide (182. 4 microg/ml) in intrapleural fluids. CDDP did not remain for a long period (free form, beta-phase half-life = 10.51 h) in the fluids, while etoposide persisted for a long period (beta-phase half-life = 62.53 h). The overall response rate was 46.2%, the median survival time 32.3 weeks, the 1-year survival rate 28.7% and the 2-year survival rate 12.8%. The most serious adverse reactions were WHO grade 3 anemia (3 patients), grade 3 nausea and vomiting (17 patients), grade 3 constipation (1 patient), grade 3 pulmonary toxicity (1 patient), grade 4 fever (1 patient), grade 3 infection (1 patient) and grade 3 mental disorder (1 patient).
Intrapleural administration of CDDP and etoposide was an effective and acceptable regimen for patients with MPE due to NSCLC.
确定胸膜腔内注射顺铂(CDDP)和依托泊苷治疗非小细胞肺癌(NSCLC)患者恶性胸腔积液(MPE)的疗效、毒性和药代动力学。
70例与NSCLC相关的MPE患者纳入本研究。68例患者在胸腔积液完全引流后24小时内,经导管成功同时给予CDDP(80mg/m²)和依托泊苷(80mg/m²),然后夹闭导管。72小时后松开导管进行引流。当胸腔内积液每天减少至20ml或更少时拔除导管。
药代动力学研究显示,胸腔积液中CDDP(游离形式,最高浓度88μg/ml)和依托泊苷(182.4μg/ml)的浓度较高。CDDP在胸腔积液中未长时间留存(游离形式,β相半衰期=10.51小时),而依托泊苷留存时间较长(β相半衰期=62.53小时)。总有效率为46.2%,中位生存时间为32.3周,1年生存率为28.7%,2年生存率为12.8%。最严重的不良反应为世界卫生组织3级贫血(3例患者)、3级恶心和呕吐(17例患者)、3级便秘(1例患者)、3级肺毒性(1例患者)、4级发热(1例患者)、3级感染(1例患者)和3级精神障碍(1例患者)。
对于NSCLC引起的MPE患者,胸膜腔内注射CDDP和依托泊苷是一种有效且可接受的治疗方案。