腹腔内应用重组人血管内皮抑制素联合氟尿嘧啶治疗恶性腹水的初步探讨

目的：观察腹腔内注入抗肿瘤新药重组人血管内皮抑制素注射液（恩度）联合氟尿嘧啶（５-ＦＵ）治疗恶性腹水的近期疗效和安全性。方法：经细胞学检查确诊的恶性腹水肿瘤患者３６例（食管癌１例、胃癌１０例、结直肠癌１５例、肝细胞癌和胰腺癌各５例），接受腹腔内注入恩度联合５-ＦＵ的方案治疗，其中５-ＦＵ１.０ｇ以及恩度６０ｍｇ匀速缓慢腹腔注入，每周重复１次；恩度治疗前和治疗中进行腹水ＶＥＧＦ的测定。按照ＷＨＯ腹水评价标准评价近期疗效，参照Ｋａｒｎｏｆｓｋｙ评分（ＫＰＳ）变化评价生活质量（ＱＯＬ），按照ＮＣＩＣＴＣ３.０版的药物毒性分级标准评价化疗不良反应。用药１周期即可评价不良反应以及近期疗效。结果：全组３６例患者中，接受恩度的周期数为２～４，中位周期数为３，总共完成的周期数为１０２个。获得ＣＲ４例，ＰＲ１３例，即客观有效率（ＲＲ）４７.２％（１７／３６）；腹水缓解持续时间１０～１０５天，中位缓解时间５１天。而ＱＯＬ改善率为５５.６％（２０／３６）。３２例患者治疗前腹水ＶＥＧＦ水平异常升高，根据其治疗后ＶＥＧＦ水平下降的比例将患者分为ＶＥＧＦ下降≥２５％组和ＶＥＧＦ下降＜２５％组，前者有效率和生活质量改善率明显比后者高（Ｐ值分别为０.００３和０.００２）。３～４级不良反应主要与化疗药物有关，包括白细胞下降５.６％（２／３６）、血小板下降２.８％（１／３６）、恶心呕吐５.６％（２／３６）以及腹泻２.８％（１／３６）。结论：腹腔内恩度联合５-ＦＵ治疗恶性腹水是一种安全、可行的治疗手段，具有较好的近期疗效，并能改善生活质量，其作用机制可能与抑制腹水ＶＥＧＦ的水平有关，值得临床进一步深入观察。

Intraperitoneal injection of recombinant human endostatin combined with fluorouracil on advanced cancers with malignant ascites

Objective：To observe the efficacy and safety of intraperitoneal recombinant human endoslatin injection（ endostar）, a new generation antiangiogenesis agent, eombined with fluorouracil on advanced cancers with malignant asciles, nethods：Endostar combined with fluorouracil were intraperitoneally administrated to the 36 cancer patients with malignant ascites confirmed by cytopathol- ogy. Sixty mg of endostar and 1. 0g fluorouracil were slowly intraperitoneally infused day 1, repeated after 7 days later. VEGF levels in malignant ascites were measured before and during the treatment. The response rate was evaluated strictly after 1 cycle according to WHO criteria, and quality of life（QOL） was evaluated according to kamofsky scores. Safety was evaluated after 1 cycle according to NCI CTC 3.0 version criteria. Results ：Totally 102 cycles were completed and the median cycle was 3. Among 36 cases, there were 4 cases achieved CR, 13 cases PR, 11 eases NR, and 8 cases PD. The objective response rate（RR） was 47.2% （ 17/36）, the median duration of response was 51 days（ 10-105 days） , QOL was improved on 20 eases（55.6% ）. Patients with a decrease of ≥25% of the baseline VEGF level had a significantly better response rate（68.4% vs. 15.4% ）, and QOL improvement rate（78.9% vs. 23.1% ） than patients with a rise or a decrease 〈 25%. The occurrence rates of G3/4 toxieities were low, including leucopenia（2/36, 5.6% ） , thrombocytopenia（ 1/36, 2. 8% ）, nausea/vomiting（2/36, 5.6% ） and diarrhea（ 1/36, 2. 8% ）. Those toxieities were mainly related to the chemotherapy agents. Conclusion：Intraperitoneal endostatin eombined with fluorouraeil results in a good response rate and im- provement of QOL for the patients with malignant aseites, which might result from the inhibition of VEGF level. The eombined regimen was low-toxic and tolerable. It is worthy of further elinical observation.