Dexamethasone, Flurbiprofen Axetil and Long-term Survival After Lung Cancer Surgery

NCT03172988 | Terminated Phase 4 DMC

• 1 other identifier: 2017[1359]-2
• Study Type: interventional
• Target: 126
• Locations: 1 country
• Sites: 2

Brief Summary

Surgical resection is the first choice treatment for patients with non-small-cell lung cancer. Despite of advances in surgical techniques, the long-term survival rate of postoperative patient is far from optimal. In a recent retrospective cohort study of the applicants, 588 patients after surgery for non-small-cell lung cancer were followed up for a medium of 5.2 years. The results showed that perioperative use of dexamethasone was associated with prolonged survival; perioperative use of flurbiprofen axetil was also associated with a slightly longer survival but not statistically significant. Further analysis showed that combined administration of dexamethasone and flurbiprofen axetil had additive effect in prolonging survival. We hypothesize that, for patients undergoing surgery for non-small-cell lung cancer, perioperative administration of dexamethasone and flurbiprofen axetil may improve long-term survival. However, evidences from randomized controlled trials are still lacking in this aspect.

Conditions

Carcinoma, Non-Small-Cell Lung; Surgery; Dexamethasone; Flubiprofen Axetil; Long-term Effects Secondary to Cancer Therapy in Adults

Keywords

Carcinoma, Non-Small-Cell Lung; Surgery; Dexamethasone; Flurbiprofen axetil; Long-term survival

Outcome Measures

Primary Outcomes (1)

• 3-year survival after surgery

  Duration of survival within 3 years after surgery.

  From end of surgery until 3 years after surgery.

Secondary Outcomes (5)

• Survival rates at different times after surgery

  At 6 months and 1, 2, 3 years after surgery.

• Duration of recurrence-free survival

  From end of surgery until 3 years after surgery.

• Recurrence-free survival rates at different times after surgery

  At 6 months and 1, 2, 3 years after surgery.

• Quality of life (WHOQOL-BREF) at 3 years after surgery

  At 3 years after surgery.

• Cognitive function (TICS-m) at 3 years after surgery

  At 3 years after surgery.

Study Arms (4)

Dexamethasone and flurbiprofen axetil

EXPERIMENTAL

Dexamethasone 10 mg is administered before anesthesia induction. Flurbiprofen axetil 50 mg is administered before the start of surgery. Postoperative analgesia is provided with a patient-controlled analgesia pump, which is established with 100 ml of 1.25 μg/ml sufentanil and 2 mg/ml flurbiprofen axetil, programmed to deliver a 2 ml bolus with a lockout interval of 6-8 min and a background infusion of 1 ml/h.

Drug: Dexamethasone; Drug: Flurbiprofen axetil

Dexamethasone and lipid microsphere

EXPERIMENTAL

Dexamethasone 10 mg is administered before anesthesia induction. Lipid microsphere 5 ml is administered before the start of surgery. Postoperative analgesia is provided with a patient-controlled analgesia pump, which is established with 100 ml of 1.25 μg/ml sufentanil and 20 ml lipid microsphere, programmed to deliver a 2 ml bolus with a lockout interval of 6-8 min and a background infusion of 1 ml/h.

Drug: Dexamethasone; Drug: Lipid microsphere

Normal saline and flurbiprofen axetil

EXPERIMENTAL

Normal saline 2 ml is administered before anesthesia induction. Flurbiprofen axetil 50 mg is administered before the start of surgery. Postoperative analgesia is provided with a patient-controlled analgesia pump, which is established with 100 ml of 1.25 μg/ml sufentanil and 2 mg/ml flurbiprofen axetil, programmed to deliver a 2 ml bolus with a lockout interval of 6-8 min and a background infusion of 1 ml/h.

Drug: Normal saline; Drug: Flurbiprofen axetil

Normal saline and lipid microsphere

PLACEBO COMPARATOR

Normal saline 2 ml is administered before anesthesia induction. Lipid microsphere 5 ml is administered before the start of surgery. Postoperative analgesia is provided with a patient-controlled analgesia pump, which is established with 100 ml of 1.25 μg sufentanil and 20 ml lipid microsphere, programmed to deliver a 2 ml bolus with a lockout interval of 6-8 min and a background infusion of 1 ml/h.

Drug: Normal saline; Drug: Lipid microsphere

Interventions

Dexamethasone DRUG

Dexamethasone 10 mg is administered before anesthesia induction.

Also known as: Dexamethasone sodium phosphate injection

Dexamethasone and flurbiprofen axetil; Dexamethasone and lipid microsphere

Normal saline DRUG

Normal saline 2 ml is administered before anesthesia induction.

Normal saline and flurbiprofen axetil; Normal saline and lipid microsphere

Flurbiprofen axetil DRUG

Flurbiprofen axetil 50 mg is administered before the start of surgery. Postoperative analgesia is provided with a patient-controlled analgesia pump, which is established with 100 ml of 1.25 μg/ml sufentanil and 2 mg/ml flurbiprofen axetil, programmed to deliver a 2 ml bolus with a lockout interval of 6-8 min and a background infusion of 1 ml/h.

Also known as: Flurbiprofen axetil injection

Dexamethasone and flurbiprofen axetil; Normal saline and flurbiprofen axetil

Lipid microsphere DRUG

Lipid microsphere 5 ml is administered before the start of surgery. Postoperative analgesia is provided with a patient-controlled analgesia pump, which is established with 100 ml of 1.25 μg/ml sufentanil and 20 ml lipid microsphere, programmed to deliver a 2 ml bolus with a lockout interval of 6-8 min and a background infusion of 1 ml/h.

Also known as: Lipid microsphere injection

Dexamethasone and lipid microsphere; Normal saline and lipid microsphere

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age from 18 to 85 years old;
• Diagnose as non-small-cell lung cancer (stage IA-IIIA);
• Plan to undergo surgical resection;
• Provide written informed consents.

You may not qualify if:

• Clinical evidences suggest remote metastasis of the primary cancer; have received radiotherapy, chemotherapy or targeted therapy before surgery; have received previous surgery for lung cancer; diagnosed with other cancer (other than lung cancer) currently or previously;
• History of therapy with glucocorticoids or immunosuppressants within 1 year, or therapy with non-steroidal anti-inflammatory drugs (NSAIDs) within 1 month;
• Allergy to glucocorticoids or NSAIDs;
• Contraindications to dexamethasone or flurbiprofen axetil, such as asthma or hives urticaria induced by aspirin or other NSAIDs; active digestive tract ulcer or bleeding, or history of repeated digestive tract ulcer or bleeding; coagulopathy (platelet count \< 50\*10\^9/L, International Normalized Ratio \> 1.4, or activated partial thromboplastin time \> 4 seconds above upper limit); current therapy with lomefloxacin, norfloxacin, or enoxacin; severe cardiac dysfunction (New York heart association class 3 or above, or Left Ventricular Ejection Fraction less than 30%) or myocardial infarction within 3 months; liver injury (transaminase higher than 2 times of upper limit); kidney injury (creatinine higher than 1.5 times of upper limit); uncontrolled severe hypertension before surgery (\> 180/120 mmHg);
• ASA physical status class IV or higher;
• Refuse to use patient-controlled analgesia pump after surgery;
• Other conditions that are considered unsuitable for study participation.

Sponsors & Collaborators

• Peking University First Hospital: lead
• Peking University Cancer Hospital & Institute: collaborator

Study Sites (2)

Peking University First Hospital

Beijing, Beijing Municipality, 100035, China

Location

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

Location

Related Publications (6)

• Neeman E, Ben-Eliyahu S. Surgery and stress promote cancer metastasis: new outlooks on perioperative mediating mechanisms and immune involvement. Brain Behav Immun. 2013 Mar;30 Suppl(Suppl):S32-40. doi: 10.1016/j.bbi.2012.03.006. Epub 2012 Apr 4.

  PMID: 22504092 BACKGROUND

• Ben-David B. Anaesthesia in Cancer Surgery: Can it Affect Cancer Survival? Curr Clin Pharmacol. 2016;11(1):4-20. doi: 10.2174/1574884711666160122093154.

  PMID: 26638975 BACKGROUND

• Cassinello F, Prieto I, del Olmo M, Rivas S, Strichartz GR. Cancer surgery: how may anesthesia influence outcome? J Clin Anesth. 2015 May;27(3):262-72. doi: 10.1016/j.jclinane.2015.02.007. Epub 2015 Mar 11.

  PMID: 25769963 BACKGROUND

• Bugada D, Bellini V, Fanelli A, Marchesini M, Compagnone C, Baciarello M, Allegri M, Fanelli G. Future Perspectives of ERAS: A Narrative Review on the New Applications of an Established Approach. Surg Res Pract. 2016;2016:3561249. doi: 10.1155/2016/3561249. Epub 2016 Jul 18.

  PMID: 27504486 BACKGROUND

• 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.

  PMID: 25305092 BACKGROUND

• Skevington SM, McCrate FM. Expecting a good quality of life in health: assessing people with diverse diseases and conditions using the WHOQOL-BREF. Health Expect. 2012 Mar;15(1):49-62. doi: 10.1111/j.1369-7625.2010.00650.x. Epub 2011 Jan 31.

  PMID: 21281412 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Dexamethasone; dexamethasone 21-phosphate; Saline Solution; flurbiprofen axetil

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Dong-Xin Wang, MD, PhD

  Peking University First Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Chairman, Department of Anesthesiology and Critical Care Medicine

Study Record Dates

• First Submitted: May 30, 2017
• First Posted: June 1, 2017
• Study Start: August 2, 2017
• Primary Completion: December 26, 2018
• Study Completion: December 26, 2018
• Last Updated: March 5, 2019

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)