Therapeutic Effect of Regional Chemotherapy in Diffuse Metastatic Cholangiocarcinoma

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2022 Aug 12

PMID 35954364

Authors

Yogesh Vashist

Kornelia Aigner

Sabine Gailhofer

Karl R Aigner

Affiliations

Soon will be listed here.

Abstract

Background: Current therapeutic options in diffuse metastatic cholangiocarcinoma (CCC) are limited with unsatisfactory results. We evaluated the efficacy of regional chemotherapy (RegCTx) using arterial infusion (AI), hypoxic stop-flow abdominal perfusion (HAP), upper abdominal perfusion (UAP) and isolated-thoracic perfusion (ITP) in 36 patients with metastatic perihilar and intrahepatic CCC.

Methods: Ten patients had previously undergone a liver resection and in 14 patients the previous systemic chemotherapy (sCTx) approach had failed. A total of 189 RegCTx cycles (90 AI, 74 UAP, 13 HAP and 12 ITP) were applied using cisplatin alone or with Adriamycin and Mitomycin C. A minimum of three cycles were applied in 75% of the study population. The response was evaluated using RECIST criteria with MediasStat 28.5.14. Mortality, morbidity and survival analysis were performed using a prospective follow-up database and SPSS-28.0.

Results: No procedure related mortality occurred. The overall morbidity was 56% and dominated by lymph fistulas at the inguinal access site. No grade III or IV haematological complication occurred. The overall response rate was 38% partial response, 41% stable and 21% progressive disease. Median overall survival was 23 months (95%CI 16.3-29.7). The RegCTx specific survival was 12 months (95%CI 6.5-17.5) in completely therapy naive patients but also in patients who had failed a sCTx attempt previously.

Conclusion: RegCTx is feasible, safe and superior to the current proposed therapeutic options in metastatic CCC. The role of RegCTx should be determined in a larger cohort of diffuse metastatic CCC patients but also at early stages especially in initially not resectable but potentially resectable patients.

References

Guadagni S, Clementi M, Valenti M, Fiorentini G, Cantore M, Kanavos E . Hypoxic abdominal stop-flow perfusion in the treatment of advanced pancreatic cancer: a phase II evaluation/trial. Eur J Surg Oncol. 2006; 33(1):72-8. DOI: 10.1016/j.ejso.2006.10.042. View

Brieau B, Dahan L, De Rycke Y, Boussaha T, Vasseur P, Tougeron D . Second-line chemotherapy for advanced biliary tract cancer after failure of the gemcitabine-platinum combination: A large multicenter study by the Association des Gastro-Entérologues Oncologues. Cancer. 2015; 121(18):3290-7. DOI: 10.1002/cncr.29471. View

Soares K, Jarnagin W . The Landmark Series: Hilar Cholangiocarcinoma. Ann Surg Oncol. 2021; 28(8):4158-4170. PMC: 9273057. DOI: 10.1245/s10434-021-09871-6. View

Banales J, Marin J, Lamarca A, Rodrigues P, Khan S, Roberts L . Cholangiocarcinoma 2020: the next horizon in mechanisms and management. Nat Rev Gastroenterol Hepatol. 2020; 17(9):557-588. PMC: 7447603. DOI: 10.1038/s41575-020-0310-z. View

Ji J, Song H, Kim R, Oh S, Lim H, Park J . Natural history of metastatic biliary tract cancer (BTC) patients with good performance status (PS) who were treated with only best supportive care (BSC). Jpn J Clin Oncol. 2015; 45(3):256-60. DOI: 10.1093/jjco/hyu210. View

Marquardt S, Kirstein M, Bruning R, Zeile M, Ferrucci P, Prevoo W . Percutaneous hepatic perfusion (chemosaturation) with melphalan in patients with intrahepatic cholangiocarcinoma: European multicentre study on safety, short-term effects and survival. Eur Radiol. 2018; 29(4):1882-1892. DOI: 10.1007/s00330-018-5729-z. View

Lamarca A, Edeline J, Goyal L . How I treat biliary tract cancer. ESMO Open. 2022; 7(1):100378. PMC: 8762076. DOI: 10.1016/j.esmoop.2021.100378. View

Jung J, Lee H, Jo J, Cho I, Chung M, Bang S . Combination Therapy with Capecitabine and Cisplatin as Second-Line Chemotherapy for Advanced Biliary Tract Cancer. Chemotherapy. 2017; 62(6):361-366. DOI: 10.1159/000479425. View

Guadagni S, Aigner K, Zoras O, Masedu F, Fiorentini G, Ricevuto E . Isolated thoracic perfusion in lung metastases from breast cancer: a retrospective observational study. Updates Surg. 2018; 71(1):165-177. DOI: 10.1007/s13304-018-00613-0. View

10.

El-Diwany R, Pawlik T, Ejaz A . Intrahepatic Cholangiocarcinoma. Surg Oncol Clin N Am. 2019; 28(4):587-599. DOI: 10.1016/j.soc.2019.06.002. View

11.

Oneda E, Abu Hilal M, Zaniboni A . Biliary Tract Cancer: Current Medical Treatment Strategies. Cancers (Basel). 2020; 12(5). PMC: 7281170. DOI: 10.3390/cancers12051237. View

12.

Aigner K, Gailhofer S, Selak E, Aigner K . Intra-arterial infusion chemotherapy versus isolated upper abdominal perfusion for advanced pancreatic cancer: a retrospective cohort study on 454 patients. J Cancer Res Clin Oncol. 2019; 145(11):2855-2862. PMC: 6800855. DOI: 10.1007/s00432-019-03019-6. View

13.

Aigner K, Selak E, Gailhofer S . Isolated thoracic perfusion with chemofiltration for progressive malignant pleural mesothelioma. Onco Targets Ther. 2017; 10:3049-3057. PMC: 5488785. DOI: 10.2147/OTT.S134126. View

14.

Edeline J, Benabdelghani M, Bertaut A, Watelet J, Hammel P, Joly J . Gemcitabine and Oxaliplatin Chemotherapy or Surveillance in Resected Biliary Tract Cancer (PRODIGE 12-ACCORD 18-UNICANCER GI): A Randomized Phase III Study. J Clin Oncol. 2019; 37(8):658-667. DOI: 10.1200/JCO.18.00050. View

15.

Aigner K, Vashist Y, Selak E, Gailhofer S, Aigner K . Efficacy of Regional Chemotherapy Approach in Peritoneal Metastatic Gastric Cancer. J Clin Med. 2021; 10(22). PMC: 8624731. DOI: 10.3390/jcm10225322. View

16.

Valle J, Wasan H, Palmer D, Cunningham D, Anthoney A, Maraveyas A . Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010; 362(14):1273-81. DOI: 10.1056/NEJMoa0908721. View

17.

Ferrucci P, Cocorocchio E, Bonomo G, Varano G, Della Vigna P, Orsi F . A New Option for the Treatment of Intrahepatic Cholangiocarcinoma: Percutaneous Hepatic Perfusion with CHEMOSAT Delivery System. Cells. 2021; 10(1). PMC: 7824743. DOI: 10.3390/cells10010070. View

18.

Primrose J, Fox R, Palmer D, Malik H, Prasad R, Mirza D . Capecitabine compared with observation in resected biliary tract cancer (BILCAP): a randomised, controlled, multicentre, phase 3 study. Lancet Oncol. 2019; 20(5):663-673. DOI: 10.1016/S1470-2045(18)30915-X. View

19.

Kasai K, Kooka Y, Suzuki Y, Suzuki A, Oikawa T, Ushio A . Efficacy of hepatic arterial infusion chemotherapy using 5-fluorouracil and systemic pegylated interferon α-2b for advanced intrahepatic cholangiocarcinoma. Ann Surg Oncol. 2014; 21(11):3638-45. DOI: 10.1245/s10434-014-3766-7. View

20.

Laface C, Laforgia M, Molinari P, Foti C, Ambrogio F, Gadaleta C . Intra-Arterial Infusion Chemotherapy in Advanced Pancreatic Cancer: A Comprehensive Review. Cancers (Basel). 2022; 14(2). PMC: 8774130. DOI: 10.3390/cancers14020450. View