a Scientific Laboratory of Cancer Chemoprevention and Oncopharmacology , N.N. Petrov Research Institute of Oncology , St. Petersburg , Russia.
b International Research Centre "Biotechnologies of the Third Millennium", ITMO University , St. Petersburg , Russia.
Int J Hyperthermia. 2018 Aug;34(5):545-550. doi: 10.1080/02656736.2017.1375161. Epub 2017 Sep 18.
The choice of an optimal administration route for intraperitoneal (IP) chemotherapy and a suitable chemotherapeutic regime in the treatment of ovarian cancer remains a controversy. We investigated survival outcomes according to catheter intraperitoneal chemotherapy (CIPC), normothermic and hyperthermic chemoperfusion (NIPEC and HIPEC) with cytostatic drugs dioxadet and cisplatin in rats with transplantable ascitic ovarian cancer.
Ascitic liquid containing 1 × 10 tumour cells was inoculated to female Wistar rats and 48 hours after rats received dioxadet and cisplatin at the maximum tolerated doses. Dioxadet at doses 1.5, 30 and 15 mg/kg and cisplatin at doses 4, 40 and 20 mg/kg body weight were administered for CIPC, NIPEC and HIPEC, respectively. Rats in the control groups received physiological saline and CIPC with physiological saline was regarded as the untreated control. The antitumor activity of the drugs was evaluated as an increase in average life expectancy (ALE). Analysis of the data was based primarily on Bayesian statistics and included Kaplan-Meier method, log-rank test and hazard ratio (HR) estimation.
Compared to the untreated control CIPC, NIPEC and HIPEC with dioxadet significantly increased ALE by 13, 15 and 17 days, whereas with cisplatin by 10, 24 and 5 days, respectively.
Dioxadet and cisplatin show similar efficacy in the CIPC route. Compared with CIPC IP chemotherapy by chemoperfusions is more effective for both the drugs. Dioxadet in HIPEC showed highest survival benefit whereas largest effect during NIPEC is achieved with cisplatin.
在卵巢癌的治疗中,选择最佳的腹腔内(IP)化疗给药途径和合适的化疗方案仍然存在争议。我们研究了顺式二氧杂环丁烷(Dioxadet)和顺铂在荷移植性腹水卵巢癌大鼠中经导管腹腔内化疗(CIPC)、常温及高温化学灌注(NIPEC 和 HIPEC)时的生存结果。
将含有 1×10 个肿瘤细胞的腹水接种于雌性 Wistar 大鼠,大鼠在接受最大耐受剂量的 Dioxadet 和顺铂 48 小时后,分别给予 1.5、30 和 15mg/kg 的 Dioxadet 及 4、40 和 20mg/kg 体重的顺铂进行 CIPC、NIPEC 和 HIPEC。对照组大鼠给予生理盐水,CIPC 中给予生理盐水作为未治疗对照。用平均预期寿命(ALE)的增加来评估药物的抗肿瘤活性。数据分析主要基于贝叶斯统计学,包括 Kaplan-Meier 法、对数秩检验和风险比(HR)估计。
与未治疗的对照相比,CIPC、NIPEC 和 HIPEC 中 Dioxadet 分别使 ALE 增加了 13、15 和 17 天,而顺铂则分别增加了 10、24 和 5 天。
Dioxadet 和顺铂在 CIPC 途径中显示出相似的疗效。与 CIPC 相比,两种药物的化学灌注 IP 化疗更有效。在 HIPEC 中,Dioxadet 显示出最高的生存获益,而在 NIPEC 中,顺铂的效果最大。