New approaches to treatment of abdominal carcinomatosis with intraperitoneal chemotherapy: Clinical and experimental study

A clinical and experimental study of efficacy of intraperitoneal chemotherapy was conducted. Clinical part of the study was performed in 82 patients with peritoneal carcinomatosis from ovarian cancer (OC). The first group of patients consisted of 46 women with recurrent OC who underwent combined treatment, including re-cytoreduction with hyperthermic intraperitoneal chemoperfusion (HIPEC): with cisplatin 100 mg/m² or with doxorubicin 25 mg/m². The second group was a control group of 40 women with recurrent OC who underwent systemic chemotherapy with the cytostatics after cytoreductive interventions. The primary end point was recurrence-free survival. The median recurrence-free survival was 6.6 months in the first group and 4.8 months in the second group (p < 0.05). Thus, recurrence-free survival in the surgery-plus-HIPEC group was higher than in the surgery-plus-systemic chemotherapy group. The experimental part of the work was carried out in the model of transplanted ascitic OC in 288 females Wistar rats in whom the OC transplant in the number of 1 к 10⁷ tumor cells was inoculated. Intraperitoneal chemotherapy was performed once 48 hours after the tumor transplantation. Dioxadet in the maximum tolerated doses was administered with intraperitoneal injection chemotherapy (IIC) with a syringe at a dose of 1.5 mg/kg of body weight and solution with the drug was pumped through the abdominal cavity with a special pump at a dose of 30 mg/kg at a temperature of 36.5-37.5 °C as normothermic intraperitoneal chemoperfusion (NIPEC) and at a dose of 15 mg/kg at a temperature 40.5-41.5 °C as HIPEC. In the control groups rats were given in the similar ways with saline solution. The antitumor effects of the treatment were evaluated by increasing the lifespan of rats. In the control group average survival rate was 15 days. Compared to the control, IIC, NIPEC and HIPEC increased the average survival rate by 85, 97 and 202 %, respectively. Thus, the most effective regimen of intraperitoneal chemotherapy is HIPEC with dioxadet.

intraperitoneal chemotherapy, normothermic and hyperthermic intraperitoneal chemoperfusion, ovarian cancer, cisplatin, dioxadet

1. Esquivel J. Cytoreductive surgery for peritoneal malignancies. Development of standards of care for the community // Surg. Oncol. Clin. N. Am.- 2007.- Vol. 16.- P. 653-666.

2. Lifante J. C., Glehen O., Cotte E. et al. Natural history of peritoneal carcinomatosis from digestive origin. In: Ceelen W. (ed.) Peritoneal carcinomatosis: a multi-disciplinary approach. Springer, New York, 2007.- P. 119-129.

3. Nissan A. Evidence-based medicine in the treatment of peritoneal carcinomatosis: past, present, and future // J. Surg. Oncol.- 2009.- Vol. 100,- P. 335-344.

4. Pingpank J.F. Diagnosis and treatment of peritoneal carcinomatosis. In: DeVita V. T., Hellman S., Rosenberg S.A. (eds).- Cancer: principles and practice of oncology, 8th edn. Lippincott, Williams and Wilkins: Philadelphia, 2008.- P. 2389-2399.

5. Беляева О. А., Беспалов В. Г., Сенчик К. Ю. и др. Химиоперфузионное лечение канцероматоза брюшной полости.- СПб., 2016.- 146 с.

6. Cascales Campos P.A., Gil M. J., Galindo Fernandez P. J., et al. Perioperative fast track program in intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery in advanced ovarian cancer // Eur. J. Surg. Oncol.- 2011.- Vol. 37.- P. 543-548.

7. Roviello F., Caruso S., Marrelli D. et al. Treatment of peritoneal carcinomatosis with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: State of the art and future developments // Surgical Oncology.- 2011.- Vol. 20.- P. 38-54.

8. Sugarbaker P. H. Peritoneum as the first-line of defense in carcinomatosis // J. Surg. Oncol.- 2007.- Vol. 95.- P. 93-96.

9. Sugarbaker P. H. Overview of peritoneal carcinomatosis // Cancerologia.-2008.- Vol. 3.- P. 119-124.

10. Chan D. L., Morris D. L., Rao A., Chua T. C. Intraperitoneal chemotherapy in ovarian cancer, a review of tolerance and efficacy // Cancer Manag. Res.- 2012.- Vol. 4.- P. 413-422.

11. Беспалов В. Г., Вышинская Е. А., Васильева И. Н. и др. Интраперитонеальная химиотерапия - путь повышения эффективности лечения рака яичника // Вопр. онкол.- 2015.- Т. 61, № 4.- C. 634-641.

12. Беспалов В. Г., Киреева Г. С., Беляева О. А. и др. Интраоперационное внутрибрюшинное химиоперфузионное лечение цисплатином и диоксадэтом на модели канцероматоза брюшной полости при раке яичника: оценка безопасности и эффективности // Вопр. онкол.- 2015.- Т. 61, № 4.- C. 647-652

13. Вышинская Е. А., Беспалов В. Г., Васильева И. Н. и др. Преимущества интраперитонеальной химиотерапии в лечении канцероматоза брюшной полости при раке яичника //Ж. акуш. и жен. болезн.- 2014.- Т. 63, № 2.- С. 28-34

14. Bespalov V. G., Kireeva G. S., Belyaeva O.A. et al. Both heat and new chemotherapeutic drug dioxadet in hyperthermic intraperitoneal chemoperfusion improved survival in rat ovarian cancer model // J. Surg. Oncol. - 2016.- Vol. 113.- P. 438-442.

15. Bespalov V. G., Kireeva G. S., Belyaeva O. A. et al. Experimental study of antitumour activity and effects on leukocyte count of intraperitoneal administration and hyperthermic intraperitoneal chemoperfusion (HIPEC) with dioxadet in a rat model of ovarian cancer. // J. Chemother.- 2016.- Vol. 28.- P. 203-209.

16. Стуков А. Н., Гершанович М. Л., Беспалов В. Г. и др. Классификация противоопухолевых препаратов // Медлайн-Экспресс. - 2012.- № 2.- C. 20-24.

17. Narod S. Can advanced-stage ovarian cancer be cured? // Nat. Rev. Clin. Oncol. - 2016.- Vol. 13.- P. 255-261.

18. Bookman M. A. Optimal primary therapy of ovarian cancer // Ann. Oncol.-2016.- Suppl. 1.- P. 58-62.

19. Гершанович М. Л., Филов В. А., Котова Д. Г. и др. Результаты кооперированного клинического изучения противоопухолевого препарата диоксадэт по II фазе // Вопр. онкол.- 1998.- T. 44, № 2.- С. 216-220.