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INTRODUCTION

Intraperitoneal chemotherapy for ovarian cancer treatment has controversial benefits as most methodologies are associated with significant morbidity. We carried out a systematic review to compare tumor response, measured by tumor weight and volume, between intraperitoneal chemotherapy delivered via drug delivery systems (DDSs) and free intraperitoneal chemotherapy in animal models of ovarian cancer. The secondary aim was to assess the toxicity of DDS-delivered chemotherapy, based on changes in animal body weight.

METHODS

Based on PRISMA and SYRCLE guidelines, we identified 38 studies for review, of which 20, were used in the meta-analysis. We evaluated outcome, through tumor volume and tumor weight and, toxicity, through animal weight. Analysis was based on drugs employed and treatment duration.

RESULTS

Most studies were performed on mice. Ovarian cancer cell lines most commonly used to induce xenografts were SKOV3 (19 studies) and A2780 (6 studies). Intraperitoneal device, also known as drug delivery systems (DDS), consisted in nanoparticles, hydrogels, lipid polymer and others. The most commonly used drugs were paclitaxel and cisplatin. Most studies used as the control treatment the same chemotherapy applied free intraperitoneally and tumor response/animal weight were evaluated weekly. There was a small benefit in overall tumor reduction in animals treated with intraperitoneal chemotherapy applied through the slow release device compared with animals treated with intraperitoneal free chemotherapy, as evaluated through tumor weight - results in standardized mean difference. (-1.06; 95% CI: -1.34, -0.78) and tumor volume (-3.72; 95% CI: -4.47, -2.97), a benefit that was seen in most weekly evaluations and for most chemotherapy drugs, such as carboplatin (tumor weight: -5.60; 95% CI: -7.83, -3.37), paclitaxel (tumor weight: -1.18; 95% CI: -1.52, -0.83), and cisplatin (tumor volume: -2.85; 95% CI: -3.66, -2.04) carboplatin (tumor volume: -12.71; 95% CI: -17.35, -8.07); cisplatin (tumor volume: -7.76; 95% CI: -9.88, -5.65); paclitaxel (tumor volume: -2.85; 95% CI: -3.66, -2.04). Regarding animal weight, there was no weight reduction in animals treated with intraperitoneal chemotherapy applied through the slow-release device compared with animals treated with intraperitoneal free chemotherapy. However, significant heterogeneity was observed in some comparisons.

CONCLUSION

slow-release devices are overall safe and effective in animal models of ovarian cancer. It was not possible to evaluate which one is the most promising device to treat ovarian cancer, because many different types were used to apply chemotherapy intraperitoneally.

SYSTEMATIC REVIEW REGISTRATION

https://www.crd.york.ac.uk/prospero/, identifier CRD42021224573.

引言

卵巢癌的腹腔内化疗的益处存在争议，因为大多数方法都伴随着显著的发病率。我们进行了一项系统综述，以比较在卵巢癌动物模型中，通过药物递送系统（DDS）进行腹腔内化疗与游离腹腔内化疗在肿瘤反应（通过肿瘤重量和体积衡量）方面的差异。次要目的是根据动物体重变化评估DDS递送化疗的毒性。

方法

根据PRISMA和SYRCLE指南，我们确定了38项研究进行综述，其中20项用于荟萃分析。我们通过肿瘤体积和肿瘤重量评估结果，通过动物体重评估毒性。分析基于所使用的药物和治疗持续时间。

结果

大多数研究在小鼠身上进行。最常用于诱导异种移植的卵巢癌细胞系是SKOV3（19项研究）和A2780（6项研究）。腹腔内装置，也称为药物递送系统（DDS），包括纳米颗粒、水凝胶、脂质聚合物等。最常用的药物是紫杉醇和顺铂。大多数研究将游离腹腔内应用相同化疗作为对照治疗，并每周评估肿瘤反应/动物体重。与接受游离腹腔内化疗的动物相比，通过缓释装置进行腹腔内化疗的动物在总体肿瘤缩小方面有轻微益处，通过肿瘤重量评估——标准化均数差结果为（-1.06；95%置信区间：-1.34，-0.78），通过肿瘤体积评估为（-3.72；95%置信区间：-4.47，-2.97），这种益处在大多数每周评估中以及大多数化疗药物（如卡铂（肿瘤重量：-5.60；95%置信区间：-7.83，-3.37）、紫杉醇（肿瘤重量：-1.18；95%置信区间：-1.52，-0.83）和顺铂（肿瘤体积：-2.85；95%置信区间：-3.66，-2.04）、卡铂（肿瘤体积：-12.71；95%置信区间：-17.35，-8.07）；顺铂（肿瘤体积：-7.76；95%置信区间：-9.88，-5.65）；紫杉醇（肿瘤体积：-2.85；95%置信区间：-3.66，-2.04））中都可见。关于动物体重，与接受游离腹腔内化疗的动物相比，通过缓释装置进行腹腔内化疗的动物体重没有减轻。然而，在一些比较中观察到显著的异质性。