Ma G Y, Bartlett D L, Reed E, Figg W D, Lush R M, Lee K B, Libutti S K, Alexander H R
Metabolism Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Cancer J Sci Am. 1997 May-Jun;3(3):174-9.
Peritoneal mesothelioma remains a difficult therapeutic challenge. Aggressive debulking combined with continuous hyperthermic peritoneal perfusion (CHPP) using cisplatin (CDDP) is a novel strategy for the treatment of peritoneal mesothelioma, allowing high regional delivery of chemotherapeutics and hyperthermia while minimizing systemic toxicity.
From June 1993 to May 1996, 10 patients with peritoneal mesothelioma (six men, four women; mean age 40 years, range 15-57) underwent tumor debulking followed by a 90-minute CHPP. CHPP parameters included mean initial CDDP of 120 micrograms/mL (range 81-166), perfusate volume 5.2 L (range 4-7), flow 1.5 L/min, intraperitoneal temperature at three locations-41.5 degrees C, 40.5 degrees C, 41.1 degrees C, and core temperature 38.4 degrees C (range 37.2 degrees C-39.5 degrees C). Nine of 10 patients had malignant peritoneal mesothelioma, eight with associated ascites, while the tenth had a symptomatic, multiply recurrent benign peritoneal mesothelioma. Nine of 10 patients were optimally debulked. Pharmacokinetics were performed on blood and perfusate samples on nine patients; CDDP levels were quantitated by atomic absorption spectroscopy.
Total perfusate cisplatin AUC was a mean of 21-fold higher (range 2- to 116-fold) than total serum cisplatin AUC, and serum CDDP behaved similarly to systemically administered CDDP. Median follow-up after CHPP is 10 months (range 2-32), with no treatment-related mortality. In eight optimally debulked patients there is no evidence of recurrent disease clinically or by CT or MRI. Seven patients with symptomatic ascites have been completely palliated.
CHPP with CDDP is well tolerated with no significant regional toxicity. Because favorable CDDP pharmacokinetics suggest the potential for enhanced CDDP tumoricidal effect during CHPP, tumor debulking and CHPP may represent an effective strategy for the treatment of peritoneal mesothelioma.
腹膜间皮瘤仍是一个治疗难题。积极的肿瘤细胞减灭术联合使用顺铂（CDDP）的持续腹腔热灌注（CHPP）是治疗腹膜间皮瘤的一种新策略，可实现化疗药物和热疗的高区域递送，同时将全身毒性降至最低。
1993年6月至1996年5月，10例腹膜间皮瘤患者（6例男性，4例女性；平均年龄40岁，范围15 - 57岁）接受了肿瘤细胞减灭术，随后进行了90分钟的CHPP。CHPP参数包括：顺铂初始平均浓度为120微克/毫升（范围81 - 166），灌注液体积5.2升（范围4 - 7），流速1.5升/分钟，三个部位的腹腔内温度分别为41.5℃、40.5℃、41.1℃，核心温度38.4℃（范围37.2℃ - 39.5℃）。10例患者中有9例患有恶性腹膜间皮瘤，8例伴有腹水，第10例患有有症状的、多次复发的良性腹膜间皮瘤。10例患者中有9例实现了最佳肿瘤细胞减灭。对9例患者的血液和灌注液样本进行了药代动力学研究；通过原子吸收光谱法定量顺铂水平。
灌注液中总顺铂AUC平均比血清总顺铂AUC高21倍（范围2至116倍），血清顺铂的表现与全身给药的顺铂相似。CHPP后的中位随访时间为10个月（范围2 - 32），无治疗相关死亡。在8例实现最佳肿瘤细胞减灭的患者中，临床、CT或MRI均未发现疾病复发迹象。7例有症状腹水的患者已完全缓解。
CDDP-CHPP耐受性良好，无明显区域毒性。由于有利的顺铂药代动力学表明在CHPP期间顺铂杀肿瘤作用可能增强，肿瘤细胞减灭术和CHPP可能是治疗腹膜间皮瘤的有效策略。
