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

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ClinicalTrials.gov Identifier: NCT03172988
Recruitment Status : Terminated (Protocol violation occurred frequently during the postoperative period.)
First Posted : June 1, 2017
Last Update Posted : March 5, 2019
Sponsor:
Collaborator:
Beijing Cancer Hospital
Information provided by (Responsible Party):
Dong-Xin Wang, Peking University First Hospital

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.

Condition or disease Intervention/treatment Phase
Carcinoma, Non-Small-Cell Lung Surgery Dexamethasone Flubiprofen Axetil Long-term Effects Secondary to Cancer Therapy in Adults Drug: Dexamethasone Drug: Normal saline Drug: Flurbiprofen axetil Drug: Lipid microsphere Phase 4

Detailed Description:

Surgical resection is the first choice treatment for patients with non-small-cell lung cancer. Although improvements of surgical techniques have reduced the incidence of complications, the long-term survival rate of postoperative patient is far from optimal. Cancer metastasis and recurrence are the main reasons that lead to long-term postoperative death. It is unavoidable that some cancer cells will be disseminated into the blood circulation or the lymphatic systems during surgery. The development of metastasis and recurrence are dependent on the balance between the immune function of the body and the cancer-promoting factors during the perioperative period.

Studies showed that surgical stress inhibits the cytotoxic effects of natural killer cells and the activity of T cells, and thus leads to immunosuppression of the body. Furthermore, perioperative management such as anesthetic techniques, anesthetics and related drugs, blood transfusion and hypothermia can also affect immune function. For example, studies showed that inhalational anesthetics and opioids aggravate immunosuppression, and may lead to worse outcome; whereas regional anesthesia and non-steroid anti-inflammatory drugs relieve immunosuppression, and thus may improve outcome. Glucocorticoids (mainly dexamethasone) are frequently used for prevention of postoperative nausea and vomiting. A recent retrospective study showed that, for patients undergoing surgery for pancreatic cancer, perioperative use of dexamethasone was associated with improved long-term survival. However, prospective randomized controlled trials are still lacking to demonstrate the relationship between perioperative management and long-term outcome in cancer patients.

A recent retrospective cohort study of the applicants recruited 588 patients after surgery for non-small-cell lung cancer and performed a postoperative follow-up for a medium of 5.2 years. After adjusting the confounding factors with multivariate logistic regression model, perioperative use of dexamethasone (medium dose 10 mg, for prevention of postoperative nausea and vomiting) was associated with prolonged survival (HR 0.70, 95% CI 0.54-0.89; P = 0.004); perioperative use of flurbiprofen axetil (medium dose 200 mg, for postoperative analgesia) was also associated with a slightly longer survival but not statistically significant (HR 0.81, 95% CI 0.63-1.03; P = 0.083). Further analysis showed that combined administration of dexamethasone and flurbiprofen axetil had additive effect in prolonging survival (compared to no use of both: adjusted HR 0.57, 95% CI 0.38-0.84, P = 0.005).

The investigators 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 126 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
Official Title: Impact of Perioperative Dexamethasone and Flurbiprofen Axetil on Long-term Survival After Surgery for Non-small Cell Lung Cancer: A 2x2 Factorial Randomized Controlled Trial
Actual Study Start Date : August 2, 2017
Actual Primary Completion Date : December 26, 2018
Actual Study Completion Date : December 26, 2018


Arm Intervention/treatment
Experimental: Dexamethasone and flurbiprofen axetil
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
Dexamethasone 10 mg is administered before anesthesia induction.
Other Name: Dexamethasone sodium phosphate injection

Drug: Flurbiprofen axetil
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.
Other Name: Flurbiprofen axetil injection

Experimental: Dexamethasone and lipid microsphere
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
Dexamethasone 10 mg is administered before anesthesia induction.
Other Name: Dexamethasone sodium phosphate injection

Drug: Lipid microsphere
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.
Other Name: Lipid microsphere injection

Experimental: Normal saline and flurbiprofen axetil
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
Normal saline 2 ml is administered before anesthesia induction.

Drug: Flurbiprofen axetil
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.
Other Name: Flurbiprofen axetil injection

Placebo Comparator: Normal saline and lipid microsphere
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
Normal saline 2 ml is administered before anesthesia induction.

Drug: Lipid microsphere
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.
Other Name: Lipid microsphere injection




Primary Outcome Measures :
  1. 3-year survival after surgery [ Time Frame: From end of surgery until 3 years after surgery. ]
    Duration of survival within 3 years after surgery.


Secondary Outcome Measures :
  1. Survival rates at different times after surgery [ Time Frame: At 6 months and 1, 2, 3 years after surgery. ]
    Survival rates at 6 months and 1, 2, 3 years after surgery.

  2. Duration of recurrence-free survival [ Time Frame: From end of surgery until 3 years after surgery. ]
    Duration of recurrence-free survival within 3 years after surgery

  3. Recurrence-free survival rates at different times after surgery [ Time Frame: At 6 months and 1, 2, 3 years after surgery. ]
    Recurrence-free survival rates at 6 months and 1, 2, 3 years after surgery.

  4. Quality of life (WHOQOL-BREF) at 3 years after surgery [ Time Frame: At 3 years after surgery. ]
    Assessed with World Health Organization Quality of Life Brief Scale (WHOQOL-BREF).

  5. Cognitive function (TICS-m) at 3 years after surgery [ Time Frame: At 3 years after surgery. ]
    Assessed with Telephone Interview for Cognitive Status-modified (TICS-m).



Information from the National Library of Medicine

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Layout table for eligibility information
Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  1. 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;
  2. History of therapy with glucocorticoids or immunosuppressants within 1 year, or therapy with non-steroidal anti-inflammatory drugs (NSAIDs) within 1 month;
  3. Allergy to glucocorticoids or NSAIDs;
  4. 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);
  5. ASA physical status class IV or higher;
  6. Refuse to use patient-controlled analgesia pump after surgery;
  7. Other conditions that are considered unsuitable for study participation.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03172988


Locations
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China, Beijing
Peking University First Hospital
Beijing, Beijing, China, 100035
Beijing Cancer Hospital
Beijing, Beijing, China, 100142
Sponsors and Collaborators
Peking University First Hospital
Beijing Cancer Hospital
Investigators
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Principal Investigator: Dong-Xin Wang, MD, PhD Peking University First Hospital

Publications:
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Responsible Party: Dong-Xin Wang, Professor and Chairman, Department of Anesthesiology and Critical Care Medicine, Peking University First Hospital
ClinicalTrials.gov Identifier: NCT03172988    
Other Study ID Numbers: 2017[1359]-2
First Posted: June 1, 2017    Key Record Dates
Last Update Posted: March 5, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Dong-Xin Wang, Peking University First Hospital:
Carcinoma, Non-Small-Cell Lung
Surgery
Dexamethasone
Flurbiprofen axetil
Long-term survival
Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Dexamethasone
Dexamethasone acetate
Flurbiprofen
Flurbiprofen axetil
Sufentanil
Anesthetics
Dexamethasone 21-phosphate
BB 1101
Central Nervous System Depressants
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents