Regional Anesthesia and Lung Cancer Recurrence

Sponsor

The Cleveland Clinic (Other)

Overall Status

Terminated

CT.gov ID

NCT01179308

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

33.5

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Test the effect of combined regiona/general anesthesia on lung cancer recurrence compared to general anesthesia alone.

Condition or Disease	Intervention/Treatment	Phase
Lung Cancer	Other: General-epidural anesthesia Other: Balanced general anesthesia and postoperative opioids	N/A

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 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.

Study Design

Study Type:

Interventional

Actual Enrollment :

67 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Supportive Care

Official Title:

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

Study Start Date :

Aug 1, 2010

Actual Primary Completion Date :

Aug 1, 2015

Actual Study Completion Date :

Aug 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: General-epidural anesthesia Epidural and general anesthesia	Other: General-epidural anesthesia General anesthesia combined with epidural anesthesia
Active Comparator: General anesthesia General anesthesia alone	Other: Balanced general anesthesia and postoperative opioids General anesthesia alone

Arm

Intervention/Treatment

Active Comparator: General-epidural anesthesia

Epidural and general anesthesia

Other: General-epidural anesthesia

General anesthesia combined with epidural anesthesia

Active Comparator: General anesthesia

General anesthesia alone

Other: Balanced general anesthesia and postoperative opioids

General anesthesia alone

Outcome Measures

Primary Outcome Measures

disease-free survival [up to 5 years after surgery]
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 [up to three years post procedure]
Secondary outcomes measured at repeated perioperative time points, include NK cell function, immune-function markers (cytokines, cortisol) and pain.
Immune function markers [for up to 3 years post procedure]
Secondary outcomes measured at repeated perioperative time points, include NK cell function, immune-function markers (cytokines, cortisol) and pain.
Pain [up to 3 years post proceudure]
Secondary outcomes measured at repeated perioperative time points, include NK cell function, immune-function markers (cytokines, cortisol) and pain.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.