Perioperative Epidural Block and Dexamethasone in Pancreatic Cancer Surgery

Pancreatic Cancer Clinical Trial

Official title:

Effect of Perioperative Epidural Block and Dexamethasone on Outcome of Patients Undergoing Pancreatic Cancer Surgery: a 2×2 Factorial Randomized Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04025840
• Other study ID #: 2019-99
• Status: Recruiting
• Phase: Phase 4
• Start date: September 11, 2019
• Est. completion date: July 2026

Study information

• Verified date: July 2021
• Source: Peking University First Hospital
• Contact: Dong-Xin Wang, MD, PhD
• Phone: 86 (10) 83572784
• Email: wangdongxin[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Pancreatic cancer remains a devastating disease with an average 5-year survival rate of about 3-5%. Previous retrospective studies showed that perioperative epidural block and/or dexamethasone are associated with improved outcome after cancer surgery. This randomized trial aims to investigate the effect of perioperative epidural block and/or dexamethasone on long-term survival in patients following pancreatic cancer surgery.

Description:

Pancreatic cancer is the fourth leading cause of cancer-related death in the world, and is estimated to become the second one in 2030. For patients with resectable pancreatic cancer, radical surgery is the first-line therapy. However, the clinical outcomes remain poor even after radical resection, as the incidence of postoperative morbidity is up to 50% and the 5-year survival rate remains below 30%. For patients undergoing major intraabdominal surgery, epidural block may provide advantages by blocking the afferent nociceptive stimuli, providing better pain relief, decreasing opioid consumption, and alleviating stress response. These effects may be helpful in preserving immune function. Some retrospective studies showed that epidural block is associated with delayed cancer recurrence/metastasis and improved survival after cancer surgery. Low-dose dexamethasone is frequently used to prevent postoperative nausea and vomiting. Recent evidences from retrospective studies suggest that perioperative dexamethasone may also affect long-term outcome after cancer surgery. For example, in patients undergoing lung cancer surgery, intraoperative dexamethasone is associated with improved recurrence-free and overall survival. Similar results are also reported in patients after pancreatic cancer surgery. The investigators hypothesize that perioperative epidural block and dexamethasone may improve survival in patients after radical pancreatic surgery. The purpose of this study is to investigate whether perioperative epidural block and/or dexamethasone can improve 2-year survival in patients after pancreatic cancer surgery.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 260
• Est. completion date: July 2026
• Est. primary completion date: July 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years to 90 Years

Eligibility

Inclusion Criteria:

1. Age =45 and <90 years;

2. Clinically diagnosed as resectable or possibly resectable pancreatic cancer and scheduled to undergo radical surgery;

3. Agreed to receive epidural block and postoperative patient-controlled analgesia;

4. Agreed to participate in the study and provided written informed consent.

Exclusion Criteria:

1. Clinical evidence of unresectable pancreatic cancer or plan to undergo biopsy;

2. Previous surgery for pancreatic cancer, scheduled to undergo resurgery for recurrence or metastasis;

3. Complicated with primary malignant tumor in other organ(s), either previously or at present;

4. Complicated with autoimmune diseases, receiving either glucocorticoids or other immunosuppressants before surgery;

5. Unable to complete preoperative evaluation due to severe dementia, language barrier, coma, or end-stage diseases;

6. Severe hepatic dysfunction (Child-Pugh C), severe renal insufficiency (serum creatinine >442 µmol/L or requirement of renal replacement therapy), or American Society of Anesthesiologists classification =V;

7. Contradictions to epidural anesthesia, including spinal malformation, history of spinal surgery, coagulation disorder, suspected infection at the site of puncture, or severe low back pain;

8. Other conditions that are considered unsuitable for study participation;

9. Refused to participate in the study.

Related Conditions & MeSH terms

• Dexamethasone
• Epidural Block
• Overall Survival
• Pancreatic Cancer
• Pancreatic Neoplasms
• Surgery

Intervention

Other:
• Epidural block
Epidural block (with 0.375% ropivacaine) is performed during surgery. Patient-controlled epidural analgesia (with a mixture of 0.12% ropivacaine and 0.5 microgram/ml sufentanyl) is provided after surgery.

Drug:
• Dexamethasone
Dexamethasone (10 mg) is administered intravenously before anesthesia induction.

Locations

Country	Name	City	State
China	Peking University First Hospital	Beijing	Beijing

Sponsors (3)

Lead Sponsor	Collaborator
Peking University First Hospital	Beijing Cancer Hospital, The Second Affiliated Hospital of Chongqing Medical University

Country where clinical trial is conducted

China, 

References & Publications (38)

Bassi C, Dervenis C, Butturini G, Fingerhut A, Yeo C, Izbicki J, Neoptolemos J, Sarr M, Traverso W, Buchler M; International Study Group on Pancreatic Fistula Definition. Postoperative pancreatic fistula: an international study group (ISGPF) definition. Surgery. 2005 Jul;138(1):8-13. Review. — View Citation

Biki B, Mascha E, Moriarty DC, Fitzpatrick JM, Sessler DI, Buggy DJ. Anesthetic technique for radical prostatectomy surgery affects cancer recurrence: a retrospective analysis. Anesthesiology. 2008 Aug;109(2):180-7. doi: 10.1097/ALN.0b013e31817f5b73. — View Citation

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12. Erratum in: CA Cancer J Clin. 2020 Jul;70(4):313. — View Citation

Call TR, Pace NL, Thorup DB, Maxfield D, Chortkoff B, Christensen J, Mulvihill SJ. Factors associated with improved survival after resection of pancreatic adenocarcinoma: a multivariable model. Anesthesiology. 2015 Feb;122(2):317-24. doi: 10.1097/ALN.0000000000000489. — View Citation

Chae BK, Lee HW, Sun K, Choi YH, Kim HM. The effect of combined epidural and light general anesthesia on stress hormones in open heart surgery patients. Surg Today. 1998;28(7):727-31. — View Citation

Chen W, Sun K, Zheng R, Zeng H, Zhang S, Xia C, Yang Z, Li H, Zou X, He J. Cancer incidence and mortality in China, 2014. Chin J Cancer Res. 2018 Feb;30(1):1-12. doi: 10.21147/j.issn.1000-9604.2018.01.01. — View Citation

Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ, He J. Cancer statistics in China, 2015. CA Cancer J Clin. 2016 Mar-Apr;66(2):115-32. doi: 10.3322/caac.21338. Epub 2016 Jan 25. — View Citation

Conroy T, Bachet JB, Ayav A, Huguet F, Lambert A, Caramella C, Maréchal R, Van Laethem JL, Ducreux M. Current standards and new innovative approaches for treatment of pancreatic cancer. Eur J Cancer. 2016 Apr;57:10-22. doi: 10.1016/j.ejca.2015.12.026. Epub 2016 Feb 4. Review. — View Citation

Cummings KC 3rd, Xu F, Cummings LC, Cooper GS. A comparison of epidural analgesia and traditional pain management effects on survival and cancer recurrence after colectomy: a population-based study. Anesthesiology. 2012 Apr;116(4):797-806. doi: 10.1097/ALN.0b013e31824674f6. — View Citation

Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026. — View Citation

Exadaktylos AK, Buggy DJ, Moriarty DC, Mascha E, Sessler DI. Can anesthetic technique for primary breast cancer surgery affect recurrence or metastasis? Anesthesiology. 2006 Oct;105(4):660-4. — View Citation

Fitzsimmons D, Johnson CD, George S, Payne S, Sandberg AA, Bassi C, Beger HG, Birk D, Büchler MW, Dervenis C, Fernandez Cruz L, Friess H, Grahm AL, Jeekel J, Laugier R, Meyer D, Singer MW, Tihanyi T. Development of a disease specific quality of life (QoL) questionnaire module to supplement the EORTC core cancer QoL questionnaire, the QLQ-C30 in patients with pancreatic cancer. EORTC Study Group on Quality of Life. Eur J Cancer. 1999 Jun;35(6):939-41. — View Citation

Giles AJ, Hutchinson MND, Sonnemann HM, Jung J, Fecci PE, Ratnam NM, Zhang W, Song H, Bailey R, Davis D, Reid CM, Park DM, Gilbert MR. Dexamethasone-induced immunosuppression: mechanisms and implications for immunotherapy. J Immunother Cancer. 2018 Jun 11;6(1):51. doi: 10.1186/s40425-018-0371-5. — View Citation

Gottschalk A, Ford JG, Regelin CC, You J, Mascha EJ, Sessler DI, Durieux ME, Nemergut EC. Association between epidural analgesia and cancer recurrence after colorectal cancer surgery. Anesthesiology. 2010 Jul;113(1):27-34. doi: 10.1097/ALN.0b013e3181de6d0d. — View Citation

Grandhi RK, Lee S, Abd-Elsayed A. The Relationship Between Regional Anesthesia and Cancer: A Metaanalysis. Ochsner J. 2017 Winter;17(4):345-361. Review. — View Citation

Guay J. The effect of neuraxial blocks on surgical blood loss and blood transfusion requirements: a meta-analysis. J Clin Anesth. 2006 Mar;18(2):124-8. — View Citation

Haughom BD, Schairer WW, Nwachukwu BU, Hellman MD, Levine BR. Does Neuraxial Anesthesia Decrease Transfusion Rates Following Total Hip Arthroplasty? J Arthroplasty. 2015 Sep;30(9 Suppl):116-20. doi: 10.1016/j.arth.2015.01.058. Epub 2015 Jun 3. — View Citation

Heerkens HD, Tseng DS, Lips IM, van Santvoort HC, Vriens MR, Hagendoorn J, Meijer GJ, Borel Rinkes IH, van Vulpen M, Molenaar IQ. Health-related quality of life after pancreatic resection for malignancy. Br J Surg. 2016 Feb;103(3):257-66. doi: 10.1002/bjs.10032. Epub 2015 Nov 19. — View Citation

Huang WW, Zhu WZ, Mu DL, Ji XQ, Nie XL, Li XY, Wang DX, Ma D. Perioperative Management May Improve Long-term Survival in Patients After Lung Cancer Surgery: A Retrospective Cohort Study. Anesth Analg. 2018 May;126(5):1666-1674. doi: 10.1213/ANE.0000000000002886. — View Citation

Kamisawa T, Wood LD, Itoi T, Takaori K. Pancreatic cancer. Lancet. 2016 Jul 2;388(10039):73-85. doi: 10.1016/S0140-6736(16)00141-0. Epub 2016 Jan 30. Review. — View Citation

Katayama H, Kurokawa Y, Nakamura K, Ito H, Kanemitsu Y, Masuda N, Tsubosa Y, Satoh T, Yokomizo A, Fukuda H, Sasako M. Extended Clavien-Dindo classification of surgical complications: Japan Clinical Oncology Group postoperative complications criteria. Surg Today. 2016 Jun;46(6):668-85. doi: 10.1007/s00595-015-1236-x. Epub 2015 Aug 20. — View Citation

Koch M, Garden OJ, Padbury R, Rahbari NN, Adam R, Capussotti L, Fan ST, Yokoyama Y, Crawford M, Makuuchi M, Christophi C, Banting S, Brooke-Smith M, Usatoff V, Nagino M, Maddern G, Hugh TJ, Vauthey JN, Greig P, Rees M, Nimura Y, Figueras J, DeMatteo RP, Büchler MW, Weitz J. Bile leakage after hepatobiliary and pancreatic surgery: a definition and grading of severity by the International Study Group of Liver Surgery. Surgery. 2011 May;149(5):680-8. doi: 10.1016/j.surg.2010.12.002. Epub 2011 Feb 12. — View Citation

Kunicka JE, Talle MA, Denhardt GH, Brown M, Prince LA, Goldstein G. Immunosuppression by glucocorticoids: inhibition of production of multiple lymphokines by in vivo administration of dexamethasone. Cell Immunol. 1993 Jun;149(1):39-49. — View Citation

Ohtsuka T, Yamaguchi K, Chijiiwa K, Kinukawa N, Tanaka M. Quality of life after pylorus-preserving pancreatoduodenectomy. Am J Surg. 2001 Sep;182(3):230-6. — View Citation

Pérez-González O, Cuéllar-Guzmán LF, Soliz J, Cata JP. Impact of Regional Anesthesia on Recurrence, Metastasis, and Immune Response in Breast Cancer Surgery: A Systematic Review of the Literature. Reg Anesth Pain Med. 2017 Nov/Dec;42(6):751-756. doi: 10.1097/AAP.0000000000000662. Review. — View Citation

Pöpping DM, Elia N, Van Aken HK, Marret E, Schug SA, Kranke P, Wenk M, Tramèr MR. Impact of epidural analgesia on mortality and morbidity after surgery: systematic review and meta-analysis of randomized controlled trials. Ann Surg. 2014 Jun;259(6):1056-67. doi: 10.1097/SLA.0000000000000237. Review. — View Citation

Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014 Jun 1;74(11):2913-21. doi: 10.1158/0008-5472.CAN-14-0155. Erratum in: Cancer Res. 2014 Jul 15;74(14):4006. — View Citation

Sandini M, Ruscic KJ, Ferrone CR, Warshaw AL, Qadan M, Eikermann M, Lillemoe KD, Fernández-Del Castillo C. Intraoperative Dexamethasone Decreases Infectious Complications After Pancreaticoduodenectomy and is Associated with Long-Term Survival in Pancreatic Cancer. Ann Surg Oncol. 2018 Dec;25(13):4020-4026. doi: 10.1245/s10434-018-6827-5. Epub 2018 Oct 8. — View Citation

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018 Jan;68(1):7-30. doi: 10.3322/caac.21442. Epub 2018 Jan 4. — View Citation

Singh PP, Lemanu DP, Taylor MH, Hill AG. Association between preoperative glucocorticoids and long-term survival and cancer recurrence after colectomy: follow-up analysis of a previous randomized controlled trial. Br J Anaesth. 2014 Jul;113 Suppl 1:i68-73. doi: 10.1093/bja/aet577. Epub 2014 Feb 27. — View Citation

Tsui BC, Rashiq S, Schopflocher D, Murtha A, Broemling S, Pillay J, Finucane BT. Epidural anesthesia and cancer recurrence rates after radical prostatectomy. Can J Anaesth. 2010 Feb;57(2):107-12. doi: 10.1007/s12630-009-9214-7. — View Citation

Wang J, Guo W, Wu Q, Zhang R, Fang J. Impact of Combination Epidural and General Anesthesia on the Long-Term Survival of Gastric Cancer Patients: A Retrospective Study. Med Sci Monit. 2016 Jul 8;22:2379-85. — View Citation

Waurick R, Van Aken H. Update in thoracic epidural anaesthesia. Best Pract Res Clin Anaesthesiol. 2005 Jun;19(2):201-13. Review. — View Citation

Wente MN, Bassi C, Dervenis C, Fingerhut A, Gouma DJ, Izbicki JR, Neoptolemos JP, Padbury RT, Sarr MG, Traverso LW, Yeo CJ, Büchler MW. Delayed gastric emptying (DGE) after pancreatic surgery: a suggested definition by the International Study Group of Pancreatic Surgery (ISGPS). Surgery. 2007 Nov;142(5):761-8. — View Citation

Winter JM, Cameron JL, Campbell KA, Arnold MA, Chang DC, Coleman J, Hodgin MB, Sauter PK, Hruban RH, Riall TS, Schulick RD, Choti MA, Lillemoe KD, Yeo CJ. 1423 pancreaticoduodenectomies for pancreatic cancer: A single-institution experience. J Gastrointest Surg. 2006 Nov;10(9):1199-210; discussion 1210-1. — View Citation

Wuethrich PY, Hsu Schmitz SF, Kessler TM, Thalmann GN, Studer UE, Stueber F, Burkhard FC. Potential influence of the anesthetic technique used during open radical prostatectomy on prostate cancer-related outcome: a retrospective study. Anesthesiology. 2010 Sep;113(3):570-6. doi: 10.1097/ALN.0b013e3181e4f6ec. — View Citation

Yeo CJ, Cameron JL. Prognostic factors in ductal pancreatic cancer. Langenbecks Arch Surg. 1998 Apr;383(2):129-33. Review. — View Citation

Yu HC, Luo YX, Peng H, Kang L, Huang MJ, Wang JP. Avoiding perioperative dexamethasone may improve the outcome of patients with rectal cancer. Eur J Surg Oncol. 2015 May;41(5):667-73. doi: 10.1016/j.ejso.2015.01.034. Epub 2015 Feb 19. — View Citation

* Note: There are 38 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Subjective sleep quality: Numeric Rating Scale	Subjective sleep quality is assessed with a Numeric Rating Scale (NRS, an 11-point scale where 0 indicates the best sleep and 10 the worst sleep).	Between 8-10 am on the first, second, and third days after surgery.
Other	Pain severity (at rest and with movement): Numeric Rating Scale	Pain severity is assessed with a Numeric Rating Scale (NRS, an 11-point scale where 0 indicates no pain and 10 the worst pain).	Between 8-10 am on the first, second, and third days after surgery.
Other	Time to ambulation after surgery.	Time to ambulation after surgery.	Up to 30 days after surgery.
Other	Time to oral intake after surgery.	Time to oral intake after surgery.	Up to 30 days after surgery.
Primary	2-year overall survival	2-year overall survival	Up to 2 years after surgery.
Secondary	Postoperative gastrointestinal complications.	Rate of postoperative gastrointestinal complications.	Up to 30 days after surgery.
Secondary	Overall postoperative complications.	Rate of overall postoperative complications.	Up to 30 days after surgery.
Secondary	Length of stay in hospital after surgery.	Length of stay in hospital after surgery.	Up to 30 days after surgery.
Secondary	All-cause 30-day mortality.	Rate of all-cause 30-day mortality.	Up to 30 days after surgery.
Secondary	Quality of life in 1- and 2-year survivors.	Quality of life is assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionaire (EORTC QLQ)-PAN26. It is a 26-item questionnaire that evaluates 9 symptoms and 5 emotional difficulties related to pancreatic cancer. Each item is scaled 0-100. High scores indicate worse symptoms and poorer quality of life.	At the end of the first and second year after surgery.
Secondary	Hospital readmission within 2 years after surgery.	Rate of hospital readmission within 2 years after surgery.	Up to 2 years after surgery.
Secondary	2-year progression-free survival	Cancer progression is evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) guideline version 1.1.	Up to 2 years after surgery.