Jaaback Kenneth, Johnson Nick, Lawrie Theresa A
Ward K3 John Hunter Hospital, Hunter New England Centre for Gynaecological Cancer, Newcastle, Australia.
Cochrane Database Syst Rev. 2011 Nov 9(11):CD005340. doi: 10.1002/14651858.CD005340.pub3.
Ovarian cancer tends to be chemosensitive and confine itself to the surface of the peritoneal cavity for much of its natural history. These features have made it an obvious target for intraperitoneal (IP) chemotherapy. Chemotherapy for ovarian cancer is usually given as an intravenous (IV) infusion repeatedly over five to eight cycles. Intraperitoneal chemotherapy is given by infusion of the chemotherapeutic agent directly into the peritoneal cavity. There are biological reasons why this might increase the anticancer effect and reduce some systemic adverse effects in comparison to IV therapy.
To determine if adding a component of the chemotherapy regime into the peritoneal cavity affects overall survival, progression-free survival, quality of life (QOL) and toxicity in the primary treatment of epithelial ovarian cancer.
We searched the Gynaecological Cancer Review Group's Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) Issue 2, 2011, MEDLINE (1951 to May 2011) and EMBASE (1974 to May 2011). We updated these searches in February 2007, August 2010 and May 2011. In addition, we handsearched and cascade searched the major gynaecological oncology journals.
The analysis was restricted to randomised controlled trials (RCTs) assessing women with a new diagnosis of primary epithelial ovarian cancer, of any FIGO stage, following primary cytoreductive surgery. Standard IV chemotherapy was compared with chemotherapy that included a component of IP administration.
We extracted data on overall survival, disease-free survival, adverse events and QOL and performed meta-analyses of hazard ratios (HR) for time-to-event variables and relative risks (RR) for dichotomous outcomes using RevMan software.
Nine randomised trials studied 2119 women receiving primary treatment for ovarian cancer. We considered six trials to be of high quality. Women were less likely to die if they received an IP component to chemotherapy (eight studies, 2026 women; HR = 0.81; 95% confidence interval (CI): 0.72 to 0.90). Intraperitoneal component chemotherapy prolonged the disease-free interval (five studies, 1311 women; HR = 0.78; 95% CI: 0.70 to 0.86). There was greater serious toxicity with regard to gastrointestinal effects, pain, fever and infection but less ototoxicity with the IP than the IV route.
AUTHORS' CONCLUSIONS: Intraperitoneal chemotherapy increases overall survival and progression-free survival from advanced ovarian cancer. The results of this meta-analysis provide the most reliable estimates of the relative survival benefits of IP over IV therapy and should be used as part of the decision making process. However, the potential for catheter related complications and toxicity needs to be considered when deciding on the most appropriate treatment for each individual woman. The optimal dose, timing and mechanism of administration cannot be addressed from this meta-analysis. This needs to be addressed in the next phase of clinical trials.
卵巢癌往往对化疗敏感，在其自然病程的大部分时间里局限于腹膜腔表面。这些特征使其成为腹腔内（IP）化疗的明显靶点。卵巢癌化疗通常通过静脉（IV）输注，在五到八个周期内反复进行。腹腔内化疗是将化疗药物直接注入腹腔。与静脉治疗相比，有生物学原因表明这可能会增强抗癌效果并减少一些全身不良反应。
确定在腹腔内加入化疗方案的一部分是否会影响上皮性卵巢癌初始治疗的总生存期、无进展生存期、生活质量（QOL）和毒性。
我们检索了妇科癌症综述小组的专业注册库、Cochrane对照试验中心注册库（CENTRAL）2011年第2期、MEDLINE（1951年至2011年5月）和EMBASE（1974年至2011年5月）。我们在2007年2月、2010年8月和2011年5月对这些检索进行了更新。此外，我们手工检索并逐级检索了主要的妇科肿瘤学杂志。
分析仅限于随机对照试验（RCT），评估任何FIGO分期的新诊断原发性上皮性卵巢癌女性患者，这些患者接受了初次细胞减灭术。将标准静脉化疗与包含腹腔内给药成分的化疗进行比较。
我们提取了总生存期、无病生存期、不良事件和生活质量的数据，并使用RevMan软件对事件发生时间变量的风险比（HR）和二分结局的相对风险（RR）进行了荟萃分析。
九项随机试验研究了2119名接受卵巢癌初始治疗的女性。我们认为六项试验质量较高。接受化疗中包含腹腔内给药成分的女性死亡可能性较小（八项研究，2026名女性；HR = 0.81；95%置信区间（CI）：0.72至0.90）。腹腔内给药成分化疗延长了无病间期（五项研究，1311名女性；HR = 0.78；95%CI：0.70至0.86）。腹腔内给药途径在胃肠道效应、疼痛、发热和感染方面有更严重的毒性，但耳毒性比静脉途径小。
腹腔内化疗可提高晚期卵巢癌的总生存期和无进展生存期。这项荟萃分析的结果提供了腹腔内化疗相对于静脉治疗相对生存获益的最可靠估计，应用于决策过程。然而，在为每位女性决定最合适的治疗方案时，需要考虑导管相关并发症和毒性的可能性。本荟萃分析无法解决最佳剂量、给药时间和给药机制问题。这需要在临床试验的下一阶段解决。
