Применение перфузионной химиотерапии в лечении различных нозологических форм злокачественных опухолей

В настоящее время при комплексном лечении злокачественных новообразований различных локализаций все шире применяются перфузионные технологии. Выполнен анализ литературных данных о возможностях применения методов интраартериальной перфузии лекарственных средств (ЛС) в лечении различных вариантов опухолей. Представлены данные об использовании этого подхода к лечению новообразований печени, холангиокарцином, опухолей поджелудочной железы, приведены сведения о возможности использования метода в лечении рака молочной железы, опухолей легких, таза, головы и шеи, центральной нервной системы.

Отмечено, что основными принципами современной перфузионной химиотерапии опухолей являются: целенаправленная гипертоническая, гипоонкотическая, ишемическая суперселективная доставка химиотерапевтического препарата без связывания с плазмой и эритроцитами; кумуляция ЛС в опухолевой ткани за счет обструкции венозного оттока из опухоли, ингибирование реабсорбции препарата; возможность осуществления относительно быстрых повторных инфузий ЛС для минимизирования пространственной реорганизации опухоли и мутаций ее клеток; защита здоровых тканей от неблагоприятного воздействия препарата. Указано, что технические аспекты метода и выбор противоопухолевых ЛС зависят от индивидуальной анатомии органа и специфических биологических характеристик опухоли, учет которых позволяет обеспечить эндоваскулярную изоляцию опухолевой ткани.

1. Lane RJ, Khin NY, Rogan CM, Magnussen JS, Ho-Shon KB, Pavlakis NF, Clarke SJ, Hugh TJ. The integration of pharmacology and pathophysiology into locoregional chemotherapy delivery via mass fluid transfer. J Control Release. 2018;28;292:18-28. DOI: 10.1016/j.jconrel.2018.10.019.

2. Kim SH, Oh JS, Chun HJ, Choi BG, Lee HG. Dual-Port versus Mono-Port Implantation for Intra-Arterial Chemoinfusion Therapy for Treatment of Hepatocellular Carcinoma in Patients with Anatomic Hepatic Artery Variation. J Vasc Interv Radiol. 2019;30(1):23-30. DOI: 10.1016/j.jvir.2018.06.006. Epub 2018 Oct 5.

3. Mei LY. Transcatheter arterial embolization of hepatic arteriovenous shunts in patients with hepatocellular carcinoma. Semin Interv Radiol. 2012;29:237-240. DOI:org/10.1055/s-0032-1326935.

4. Takayasu K, Arii S, Sakamoto M, Matsuyama Y, Kudo M, Ichida T, Nakashima O, Matsui O, Izumi N, Ku Y, Kokudo N, Makuuchi M. Clinical implication of hypovascular hepatocellular carcinoma studied in 4,474 patients with solitary tumour equal or less than 3 cm. Liver Int. 2013;33:762-770. DOI:org/10.1111/liv.12130.

5. Martin RCG, Geller D, Espat J, Kooby D, Sellars M, Goldstein R, Imagawa D, Scoggins C. Safety and efficacy of trans arterial chemoembolization with drugeluting beads in hepatocellular cancer: a systematic review. HepatoGastroenterology. 2012;59:255-260. DOI: org/10.5754/hge10240.

6. Bester L, Meteling B, Pocock N, Saxena A, Chua T, Morris D. Radioembolisation with Yttrium-90 microspheres: an effective treatment modality for unresectable liver metastases. J Med Imaging Radiat Oncol. 2013;57:72-80. DOI: org/10.1111/j.1754-9485.2012.02459.x.

7. Gulec SA, Pennington K, Wheeler J, Barot TC, Suthar RR, Hall M, Schwartzentruber D. Yttrium-90 microsphere-selective internal radiation therapy with chemotherapy (chemo-SIRT) for colorectal cancer liver metastases: an in vivo double-arm-controlled phase II trial. Am J Clin Oncol. 2013;36:455-460. DOI: org/10.1097/COC.0b013e3182546c50.

8. De Jong LAW, Elekonawo FMK, de Reuver PR, Bremers AJA, de Wilt JHW, Jansman FGA, Ter Heine R, van Erp NP. Hyperthermic intraperitoneal chemotherapy with oxaliplatin for peritoneal carcinomatosis: a clinical pharmacological perspective on a surgical procedure. Br J Clin Pharmacol. 2019;85(1):47-58. DOI: 10.1111/bcp.13773. Epub 2018 Oct 25. Review.

9. Endo I, Gonen M, Yopp A, Dalal K, Zhou O, Klimstra D et al. Jarnagin, Intrahepatic cholangiocarcinoma: rising frequency, improved survival, and determinants of outcome after resection. Ann Surg. 2008;248:84-96. https://doi.org/10.1097/SLA.0b013e318176c4d3.

10. Vollmar B, Menger MD. The hepatic microcirculation: mechanistic contributions and therapeutic targets in liver injury and repair. Physiol Rev. 2009;89:1269-1339. DOI: org/10.1152/physrev.00027.2008.

11. McEwan PE, Bailey L, Trost D, Scull C, Keating JH, Williams M, Guttendorf RJ. Percutaneous Hepatic Perfusion With Filtered Melphalan for Localized Treatment of Metastatic Hepatic Disease: A Risk Assessment. Int J Toxicol. 2018;19:1091581818811306. DOI: 10.1177/1091581818811306.

12. O'Dwyer PJ, Catalano RB. Uridine Diphosphate Glucuronos-yltransferase (UGT) 1A1 and Irinotecan: Practical Pharmacogenomics Arrives in Cancer Therapy. J Clin Oncol. 2006;24:4534-4538. DOI: org/10.1200/JCO.2006.07.3031.

13. Pommier Y. Drugging topoisomerases: lessons and challenges. ACS Chem Biol. 2013;8:82-95. DOI: org/10.1021/cb300648v.

14. Takahashi H, Ohigashi H, Gotoh K, Marubashi S, Yamada T, Murata M. Preoperative gemcitabine-based chemoradiation therapy for resectable and borderline resectable pancreatic cancer. Ann Surg. 2013;258:1040-1050. DOI: org/10.1097/SLA.0b013e31829b3ce4.

15. Takahashi H, Ohigashi H, Ishikawa O, Gotoh K, Yamada T, Nagata S. Perineural invasion and lymph node involvement as indicators of surgical outcome and pattern of recurrence in the setting of preoperative gemcitabine-based chemoradiation therapy for resectable pancreatic cancer. Ann Surg. 2012;255:95-102. DOI: org/10.1097/SLA.0b013e31823d813c.

16. Speer AG, Thursfield VJ, Torn-Broers Y, Jefford M. Pancreatic cancer: surgical management and outcomes after 6 years of follow-up. Med J Aust. 2012;196:511-515. DOI: org/10.5694/mja11.10890.

17. Iorgulescu DG, Ling S, Nikfarjam M, Fink M, Jones M Christophi, Results of pancreatic resection associated with portal vein resection in an Australian tertiary care centre, ANZ J Surg. 2015;85:270-273. DOI: org/10.1111/ans.12585.

18. Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, Seay T, Tjulandin SA, Ma WW, Saleh MN, Harris M, Reni M, Dowden S, Laheru D, Bahary N, Ramanathan RK, Tabernero J, Hidalgo M, Goldstein D, Van Cutsem E, Wei X, Iglesias J, Renschler MF. Renschler, Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369:1691-1703. DOI: org/10.1056/NEJMoa1304369.

19. Stephens FO. Why use regional chemotherapy? Principles and pharmacokinetics. Reg Cancer Treat. 1988;1:4-10.

20. Lane RJ, Khin NY, Pavlakis N, Hugh TJ, Clarke SJ, Magnussen J, Rogan C, Flekser RL. Challenges in chemotherapy delivery: comparison of standard chemotherapy delivery to locoregional vascular mass fluid transfer. Future Oncol. 2018;14:647-663. DOI: org/10.2217/fon-2017-0546.

21. Fiorentini G, Tsetis D, Varveris D, Montagnani F, Kalogeraki A, Mambrini A, Athanasakis H, Aliberti C, Guadagni S, Zoras O. Induction intra-arterial chemotherapy (IAC) with epirubicin and mitoxantrone in locally advanced breast cancer, in: K.R. Aigner, F.O. Stephens (Eds.), Induction Chemother, Springer Berlin Heidelberg, Berlin, Heidelberg. 2011:139-149. DOI: org/10.1007/9783-642-18173-3-10.

22. Milne EN. Pulmonary metastases: vascular supply and diagnosis. Int J Radiat Oncol Biol Phys. 1976;1;739-742.

23. Guadagni S, Aigner K, Zoras O, Masedu F, Fiorentini G, Ricevuto E, Deraco M, Clementi M. Isolated thoracic perfusion in lung metastases from breast cancer: a retrospective observational study. Updates Surg. 2018 Dec 12. DOI: 10.1007/s13304-018-00613-0.

24. Grootenboers MJ, Hendriks JM, van Boven WJ, Knibbe CA, van Putte B, Stockman B, De Bruijn E, Vermorken JB, Van Schil PE, Schramel FM. Pharmacokinetics of isolated lung perfusion with melphalan for resectable pulmonary metastases, a phase I and extension trial. J Surg Oncol. 2007;96:583-589. DOI: org/10.1002/jso.20838.

25. Vogl TJ, Lehnert T, Zangos S, Eichler K, Hammerstingl R, Korkusuz H, Lindemayr S. Transpulmonary chemoembolization (TPCE) as a treatment for unresectable lung metastases. Eur Radiol. 2008;18:2449-2455. https://doi.org/10.1007/s00330-008-1056-0.

26. Burt ME, Liu D, Abolhoda A, Ross H, Kaneda Y, Jara E et al. Isolated lung perfusion for patients with unresectable metastases from sarcoma: a phase I trial. Ann Thorac Surg. 2000;69:1542-1549.

27. Schroder C, Fisher S, Pieck AC, Muller A, Jaehde U, Kirchner U et al. Technique and results of hyperthermic (41 degrees C) isolated lung perfusion with high-doses of cisplatin for the treatment of surgically relapsing or unresectable lung sarcoma metastasis. Eur J Cardiothorac Surg. 2002;22:41-46.

28. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68:7-30. DOI: org/10.3322/caac.21442.

29. Sanchez-Salas R, Flamand V, Cathelineau X. Preventing complications in robotic prostatic surgery. Eur Urol Suppl. 2010;9:388-393. DOI: org/10.1016/j.eursup.2010.02.003.

30. Do NL, Nagle D, Poylin VY. Radiation proctitis: current strategies in management. Gastroenterol Res Pract. 2011;917941. DOI: org/10.1155/2011/917941.

31. Gemmete JJ. Complications associated with selective high-dose intraarterial cisplatin and concomitant radiation therapy for advanced head and neck cancer. J Vasc Interv Radiol. 2003;14:743-748.

32. Smith WS, Sung G, Starkman S, Saver JL, Kidwell CS, Gobin YP, Lutsep HL, Nesbit GM, Grobelny T, Rymer MM, Silverman IE, Higashida RT, Budzik RF, Marks MP. Safety and efficacy of mechanical embolectomy in acute ischemic stroke: results of the MERCI trial. Stroke. 2005;36:1432-1438. DOI: org/10.1161/01.STR.0000171066.25248.1d.

33. Homma A, Furuta Y, Suzuki F, Oridate N, Hatakeyama H, Nagahashi T, Ushikoshi S, Asano T, Nishioka T, Shirato H, Fukuda S. Rapid superselective high-dose cisplatin infusion with concomitant radiotherapy for advanced head and neck cancer. Head Neck. 2005;27:65-71. DOI: org/10.1002/hed.20116.

34. Dubel GJ, Ahn SH, Soares GM. Contemporary endovascular embolotherapy for meningioma. Semin Intervent Radiol. 2013;30:263-277. DOI: org/10.1055/s-0033-1353479.

35. Zhou Z, Lu R. Gadolinium-based contrast agents for magnetic resonance cancer imaging, Wiley Interdiscip. Rev Nanomed Nanobiotechnol. 2013;5:1-18. https://doi.org/10.1002/wnan.1198.

36. Janson CG. The curious case of intracranial lymphatics. Sci Transl Med. 2015;7:300ec137. DOI: 10.1126/scitranslmed.aad0225.