Hirte H W, Miller D, Tonkin K, Findlay B, Capstick V, Murphy J, Buckman R, Carmichael J, Levine M, Hill W
Ontario Cancer Treatment and Research Foundation, Hamilton Regional Cancer Centre, Canada.
Gynecol Oncol. 1997 Jan;64(1):80-7. doi: 10.1006/gyno.1996.4529.
Previous phase I and II studies of intraperitoneal recombinant human tumor necrosis factor-alpha (rhTNF-alpha) suggested a high degree of efficacy in reducing or eliminating ascitic fluid. To more accurately determine the efficacy of this agent, the role of paracentesis versus paracentesis plus intraperitoneal rhTNF-alpha was studied in a randomized trial.
Thirty-nine patients with symptomatic ascites with a volume of > 1000 ml from recurrent epithelial ovarian carcinoma or primary peritoneal carcinoma, which was refractory to standard therapy, were randomized either to receive 0.06 mg/m2 rhTNF-alpha (Knoll, Canada) (the dose determined optimal from phase I and II studies) intraperitoneally after drainage of fluid or to receive drainage alone. A maximum of three treatments were given at weekly intervals. Eighteen patients were randomized to receive rhTNF-alpha.
None of 18 evaluable rhTNF-alpha patients had either a complete response (CR) (no clinical evidence of ascites and < 400 ml of fluid on ultrasound) or a partial response (PR) (asymptomatic ascites and < or = 1000 ml of fluid ultrasound). There were no CRs or PRs in the 17 evaluable patients who received drainage alone. The intraperitoneal infusion of rhTNF-alpha was generally well tolerated. Moderate to severe toxicity consisted of pain/discomfort in 42.1%, fever/chills in 36.9%, nausea/vomiting in 10.5%, edema in 10.5%, and hypotension in 5.3% of patients receiving rhTNF-alpha.
rhTNF-alpha, as given in this study, was not effective in preventing recurrence of ascites in this patient population.
先前关于腹腔内注射重组人肿瘤坏死因子-α（rhTNF-α）的I期和II期研究表明，其在减少或消除腹水方面具有高度疗效。为了更准确地确定该药物的疗效，在一项随机试验中研究了腹腔穿刺术与腹腔穿刺术加腹腔内rhTNF-α的作用。
39例有症状性腹水（腹水量>1000 ml）且来自复发性上皮性卵巢癌或原发性腹膜癌且对标准治疗无效的患者，被随机分为两组，一组在放液后腹腔内接受0.06 mg/m² rhTNF-α（加拿大诺尔公司生产）（该剂量由I期和II期研究确定为最佳剂量），另一组仅接受放液治疗。每周最多进行三次治疗。18例患者被随机分配接受rhTNF-α治疗。
18例可评估的接受rhTNF-α治疗的患者中，无一例出现完全缓解（CR）（无腹水临床证据且超声显示腹水量<400 ml）或部分缓解（PR）（无症状性腹水且超声显示腹水量≤1000 ml）。17例仅接受放液治疗的可评估患者中也没有出现CR或PR。腹腔内输注rhTNF-α一般耐受性良好。接受rhTNF-α治疗的患者中，中度至重度毒性包括疼痛/不适（42.1%）、发热/寒战（36.9%）、恶心/呕吐（10.5%）、水肿（10.5%）和低血压（5.3%）。
本研究中使用的rhTNF-α对预防该患者群体腹水复发无效。
