The Effect of Combined General/Regional Anesthesia on Cancer Recurrence in Patients Having Lung Cancer Resections

The primary hypothesis is that disease-free survival is improved in patients undergoing resection for tumor thought to be stage I-III primary non-small cell lung cancer in patients with combined general-epidural anesthesia & analgesia as compared to patients receiving general anesthesia and postoperative patient-controlled opioid analgesia. Patients having surgery for resection of potentially curable lung cancer will be randomized to combined general and epidural anesthesia or general anesthesia with opioid analgesia. The primary outcome will be disease-free survival.

Study Overview

• Status: Withdrawn
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Procedure: Combined general/epidural anesthesia; Procedure: General anesthesia with opioid analgesia

Detailed Description

Surgery is the primary treatment of lung cancer, but surgery releases tumor cells into the systemic circulation. Whether this minimal residual disease results in clinical metastases is a function of host defense. At least three perioperative factors shift the balance toward initiation and progression of minimal residual disease.

1. Surgery per se depresses cell-mediated immunity, reduces concentrations of tumor-related anti-angiogenic factors (e.g., angiostatin and endostatin), and increases concentrations of pro-angiogenic factors such as VEGF.
2. Anesthesia impairs numerous immune functions, including neutrophil, macrophages, dendritic cells, T-cell, and NK-cell functions.
3. Opioid analgesics inhibit both cellular and humoral immune function in humans, and promote tumor growth in rodents.

The primary hypothesis is that disease-free survival is improved in patients undergoing resection for tumor thought to be stage I-III primary non-small cell lung cancer in patients with combined general-epidural anesthesia & analgesia as compared to patients receiving general anesthesia and postoperative patient-controlled opioid analgesia. Patients having surgery for resection of potentially curable lung cancer will be randomized to combined general and epidural anesthesia or general anesthesia with opioid analgesia. The primary outcome will be disease-free survival.

The effect of combined epidural/general anesthesia versus general anesthesia with opioid analgesia on the primary outcome of disease-free survival (time to the earlier or recurrence or death from any cause) will be assessed uni-variably with Kaplan-Meier analyses and multivariably (primary analysis) with a Cox proportional hazards regression model adjusting for known risk factors for recurrence, including tumor stage, size of tumor, age, sex, receipt of chemotherapy before or after surgery, and clinical site. As usual for this type of analysis, stopping criteria will be based on number of outcome events rather than enrollment.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • Shanghai Chest Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Tumor thought to be primary non-small cell lung cancer (stage 1-3) as determined according to the IASLC Lung Cancer Staging Project[ref];
2. Scheduled for potentially curative tumor resection;
3. Written informed consent, including willingness to be randomized to epidural anesthesia/analgesia plus general anesthesia or to general anesthesia and postoperative opioid analgesia;
4. ASA physical status 1-3.

Exclusion Criteria:

1. Any contraindication to epidural anesthesia, (including coagulopathy, abnormal anatomy).
2. Any contraindication to midazolam, propofol, sevoflurane, fentanyl, morphine, or hydromorphone.
3. Age <18 or >85 years old.
4. Other cancer not believed by the attending surgeon to be in long-term remission.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Combined general/epidural anesthesia; Combined general/epidural anesthesia and analgesia. General anesthesia may include propofol, isoflurane, sevoflurane, and other drugs. Epidural anesthesia will include bupivacaine and other local anesthetics.	Procedure: Combined general/epidural anesthesia; Combined general/epidural anesthesia and analgesia. General anesthesia may include propofol, isoflurane, sevoflurane, and other drugs. Epidural anesthesia will include bupivacaine and other local anesthetics.
Experimental: General anesthesia with opioid analgesia; General anesthesia with routine drugs and intravenous PCA opioid analgesia. General anesthesia may include propofol, isoflurane, sevoflurane, and other drugs.	Procedure: General anesthesia with opioid analgesia; General anesthesia with routine drugs and intravenous patient controlled opioid analgesia. General anesthesia may include propofol, isoflurane, sevoflurane, and other drugs.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cancer-free survival	Patients who remain alive without known lung cancer recurrence	3 years or as available

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain intensity	Time-weighted average pain scores over initial two days of hospitalization.	2 days
SF-12 Health Survey		6, 12, 24, and 36 months
McGill Pain Questionnaire		6, 12, 24, and 36 months
Neuropathic Pain Questionnaire		6, 12, 24, and 36 months
Opioid use	Total opioid use	2 days

Collaborators and Investigators

• Sponsor: The Cleveland Clinic
• Collaborators: Shanghai Chest Hospital
• Investigators: Study Chair: Daniel I Sessler, MD, The Cleveland Clinic

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: June 20, 2016
• First Submitted That Met QC Criteria: July 18, 2016
• First Posted (Estimated): July 21, 2016

Study Record Updates

• Last Update Posted (Actual): June 20, 2024
• Last Update Submitted That Met QC Criteria: June 18, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Cancer; Epidural anesthesia; General anesthesia
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Disease Attributes; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Recurrence; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics
• Other Study ID Numbers: 091051

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO