The Effect of Adding Intraoperative Regional Anesthesia on Cancer Recurrence in Patients Undergoing Lung Cancer Resection

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2011 by Outcomes Research Consortium
Sponsor:
Information provided by:
Outcomes Research Consortium
ClinicalTrials.gov Identifier:
NCT01179308
First received: August 10, 2010
Last updated: August 18, 2011
Last verified: August 2011
  Purpose

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 lymphocytes (T-cell), and Natural killer cell (NK-cell) functions. (3) Opioid analgesics inhibit both cellular and humoral immune function in humans, and promote tumor growth in rodents. Regional analgesia attenuates each of these adverse effects. For example, regional anesthesia largely prevents the neuroendocrine stress response to surgery by blocking afferent neural transmission. With combined regional and general anesthesia/analgesia, the amount of general anesthetic required is much reduced — as is, presumably, immune suppression. And finally, regional analgesia provides superb pain relief, essentially obliterating the need for postoperative opioids. Animal studies show that regional anesthesia improves natural kill cell function and reduces the metastatic burden in animals inoculated with carcinoma cells. Preliminary retrospective data in cancer patients showed, that paravertebral analgesia for breast cancer surgery reduced risk of recurrence or metastasis by 40% during a 2.5 to 4-year follow-up period.

The investigators thus propose to evaluate the effect of combined epidural-general anesthesia compared to general anesthesia on cancer recurrence semi-annually over a period of 5 years.


Condition Intervention
Lung Cancer
Other: General-epidural anesthesia and analgesia
Other: Balanced general anesthesia and postoperative opioids

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Supportive Care
Official Title: The Effect of Adding Intraoperative Regional Anesthesia on Cancer Recurrence in Patients Undergoing Lung Cancer Resection

Resource links provided by NLM:


Further study details as provided by Outcomes Research Consortium:

Primary Outcome Measures:
  • disease-free survival [ Time Frame: up to 5 years after surgery ] [ Designated as safety issue: No ]
    The effect of regional versus general anesthesia on the primary outcome of disease-free survival (time to the earlier or recurrence or death from any cause)


Secondary Outcome Measures:
  • NK cell function [ Time Frame: up to three years post procedure ] [ Designated as safety issue: No ]
    Secondary outcomes measured at repeated perioperative time points, include NK cell function, immune-function markers (cytokines, cortisol) and pain.

  • Immune function markers [ Time Frame: for up to 3 years post procedure ] [ Designated as safety issue: No ]
    Secondary outcomes measured at repeated perioperative time points, include NK cell function, immune-function markers (cytokines, cortisol) and pain.

  • Pain [ Time Frame: up to 3 years post proceudure ] [ Designated as safety issue: No ]
    Secondary outcomes measured at repeated perioperative time points, include NK cell function, immune-function markers (cytokines, cortisol) and pain.


Estimated Enrollment: 1532
Study Start Date: August 2010
Estimated Study Completion Date: August 2018
Estimated Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: General-epidural anesthesia and analgesia
General anesthesia will be induced with 1-3 µg/kg fentanyl (to a maximum of 150 µg) and 2-4 mg/kg propofol. Tracheal intubation will be facilitated by succinylcholine or a non-depolarizing muscle relaxant. Anesthesia will be maintained with sevoflurane in (80%-100%) oxygen, balance nitrogen, and fentanyl (0.5-1 µg/kg). The lungs will be mechanically ventilated to maintain end-tidal PCO2 near 40 mmHg. Normothermia — a distal esophageal temperature of 36°C — will be maintained with forced-air warming.
Other: General-epidural anesthesia and analgesia
General anesthesia will be induced with 1-3 µg/kg fentanyl (to a maximum of 150 µg) and 2-4 mg/kg propofol. Tracheal intubation will be facilitated by succinylcholine or a non-depolarizing muscle relaxant. Anesthesia will be maintained with sevoflurane in (80%-100%) oxygen, balance nitrogen, and fentanyl (0.5-1 µg/kg). The lungs will be mechanically ventilated to maintain end-tidal PCO2 near 40 mmHg. Normothermia — a distal esophageal temperature of 36°C — will be maintained with forced-air warming.
Active Comparator: Balanced general anesthesia and postoperative opioids
Patients will be pre-medicated with 0-3 mg IV midazolam and/or 0-2 μg/kg IV fentanyl. Prophylactic antibiotics will be given per surgical routine. An epidural catheter will be positioned at T4-T8 level before induction of anesthesia.
Other: Balanced general anesthesia and postoperative opioids
Patients will be pre-medicated with 0-3 mg IV midazolam and/or 0-2 μg/kg IV fentanyl. Prophylactic antibiotics will be given per surgical routine. An epidural catheter will be positioned at T4-T8 level before induction of anesthesia.

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Primary non-small cell lung cancer (stage 1-3) as determined according to the IASLC Lung Cancer Staging Project;
  • Scheduled for potentially curative tumor resection;
  • Written informed consent, including willingness to be randomized to epidural anesthesia/analgesia plus general anesthesia or to general anesthesia and postoperative opioid analgesia.

Exclusion Criteria:

  • Any contraindication to epidural anesthesia, (including coagulopathy, abnormal anatomy).
  • Any contraindication to midazolam, propofol, sevoflurane, fentanyl, morphine, or hydromorphone.
  • Age < 18 or > 85 years old.
  • Other cancer not believed by the attending surgeon to be in long-term remission.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01179308

Contacts
Contact: Andrea Kurz, M.D. 216-445-9924 ak@or.org
Contact: Gretchen Upton 216-444-3289 uptong@ccf.org

Locations
United States, Ohio
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44195
Contact: Andrea Kurz, M.D.    216-445-9924    ak@or.org   
Principal Investigator: Andrea Kurz, M.D.         
Sponsors and Collaborators
Outcomes Research Consortium
Investigators
Principal Investigator: Andrea Kurz, M.D. The Cleveland Clinic
  More Information

No publications provided

Responsible Party: Andrea Kurz, MD, Cleveland Clinic
ClinicalTrials.gov Identifier: NCT01179308     History of Changes
Obsolete Identifiers: NCT00999726
Other Study ID Numbers: 10-610
Study First Received: August 10, 2010
Last Updated: August 18, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by Outcomes Research Consortium:
regional analgesia
routine general anesthesia
immune system response
lung cancer (stage 1-3)

Additional relevant MeSH terms:
Anesthetics
Lung Neoplasms
Recurrence
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Disease Attributes
Pathologic Processes
Neuromuscular Nondepolarizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Neuromuscular Blocking Agents
Neuromuscular Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on September 22, 2014