The Effect of Adding Intraoperative Regional Anesthesia on Cancer Recurrence in Patients Undergoing Lung Cancer Resection
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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 |
- 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)
- 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 |
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| Contact: Andrea Kurz, M.D. | 216-445-9924 | ak@or.org |
| Contact: Gretchen Upton | 216-444-3289 | uptong@ccf.org |
| 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. | |
| 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 |
Analgesics, Opioid 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 Analgesics Sensory System Agents |
ClinicalTrials.gov processed this record on May 19, 2013