Regional Anesthesia and Breast Cancer Recurrence
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| ClinicalTrials.gov Identifier: NCT00418457 |
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Recruitment Status :
Completed
First Posted : January 4, 2007
Results First Posted : June 16, 2020
Last Update Posted : June 16, 2020
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Breast Neoplasms | Drug: General anesthesia and opioids Drug: Regional analgesia and propofol | Phase 3 |
Surgery is the primary and most effective treatment of breast cancer, but residual disease in the form of scattered micrometastases and tumor cells are usually unavoidable. Whether minimal residual disease results in clinical metastases is a function of host defense and tumor survival and growth. At least three perioperative factors shift the balance toward progression of minimal residual disease:
- Surgery per se depresses cell-mediated immunity, reduces concentrations of tumor-related anti-angiogenic factors (e.g., angiostatin and endostatin), increases concentrations of pro-angiogenic factors such as VEGF, and releases growth factors that promote local and distant growth of malignant tissue.
- Anesthesia impairs numerous immune functions, including those of neutrophils, macrophages, dendritic cells, T-cell, and natural killer cells.
- Opioid analgesics inhibit both cellular and humoral immune function in humans, increase angiogenesis, and promote breast tumor growth in rodents.
However, regional analgesia attenuates or prevents each of these adverse effects by largely preventing the neuroendocrine surgical stress response, eliminating or reducing the need for general anesthesia, and minimizing opioid requirement. Animal studies indicate that regional anesthesia and optimum postoperative analgesia independently reduce the metastatic burden in animals inoculated with breast adenocarcinoma cells following surgery. Preliminary data in cancer patients are also consistent: paravertebral analgesia for breast cancer surgery reduced risk of recurrence or metastasis approximately four-fold (95% CI of estimated hazard ratio is 0.71 - 0.06) during a 2.5 to 4-year follow-up period compared to opioid analgesia. The investigators will thus test the hypothesis that recurrence after breast cancer surgery is lower with regional anesthesia/analgesia than with general anesthesia and opioid analgesia.
In this multi-center trial, Stage 1-3 patients having mastectomies will be randomly assigned to thoracic epidural or paravertebral anesthesia/analgesia, or to general anesthesia and opioid analgesia. As with all time-to-event trials, interim and final analyses are based on the number of outcome events (recurrences in this case) rather than enrollment. The number of patients required is just an estimate and varies based on actual recurrence rates which in turn depend on patients' stage and grade, and ancillary treatments. There will be three evenly spaced interim analyses and a final analysis at 351 recurrences. Confirming our hypothesis will indicate that a minor modification to anesthetic management, one that can be implemented with little risk or cost, will reduce the risk of cancer recurrence - a complication that is often ultimately lethal.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 2108 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Prevention |
| Official Title: | Regional Anesthesia and Breast Cancer Recurrence |
| Study Start Date : | January 2007 |
| Actual Primary Completion Date : | February 2018 |
| Actual Study Completion Date : | December 2019 |
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: General anesthesia and opioid
General anesthesia followed by opioid administration
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Drug: General anesthesia and opioids
General anesthesia, usually with sevoflurane, and opioid analgesia
Other Name: General anesthesia |
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Active Comparator: Regional analgesia and propofol
Regional anesthesia and analgesia (either epidural or paravertebral) combined with propofol
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Drug: Regional analgesia and propofol
Regional anesthesia and analgesia (either epidural or paravertebral), combined with deep sedation or general anesthesia
Other Name: Regional analgesia |
- Number of Participants Who Had Breast Cancer Recurrence After Breast Cancer Surgery [ Time Frame: up to 10 years ]time to breast cancer recurrence from the end of surgery.
- Number of Participants That Experienced Post-Surgical Pain [ Time Frame: 6 months and 1 year ]Brief Pain Inventory is used to evaluate with values of any pain vs. no pain (binary)
- Number of Participants That Experienced Neuropathic Pain After Surgery [ Time Frame: 6 month and 1 year ]neuropathic pain is a binary outcome: any pain vs. no pain
- SF-12 PCS Score [ Time Frame: 6 month and 1 year ]Physical and Mental Health Composite Scores (PCS & MCS) are computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.
- SF-12 MCS Score [ Time Frame: 6 month and 1 year ]Physical and Mental Health Composite Scores (PCS & MCS) are computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.
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| Ages Eligible for Study: | 18 Years to 85 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Primary breast cancer without known extension beyond the breast and axillary nodes (i.e. believed to be Tumor Stage 1-3, Nodes 0-2)
- Scheduled for unilateral or bilateral mastectomy with or without implant (isolated "lumpectomy" will not qualify)
- Isolated "lumpectomy" with axillary node dissection (anticipated removal of at least five nodes)
- Written informed consent, including willingness to be randomized to morphine or regional analgesia
Exclusion Criteria:
- Previous surgery for breast cancer (except diagnostic biopsies)
- Inflammatory breast cancer
- Age < 18 or > 85 years old
- Scheduled free flap reconstruction
- ASA Physical Status ≥ 4
- Any contraindication to epidural or paravertebral anesthesia and analgesia (including coagulopathy, abnormal anatomy)
- Any contraindication to midazolam, propofol, sevoflurane, fentanyl, or morphine
- Other cancer not believed by the attending surgeon to be in long-term remission
- Systemic disease believed by the attending surgeon to present ≥ 25% two-year mortality
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): NCT00418457
| United States, Ohio | |
| Cleveland Clinic Foundation | |
| Cleveland, Ohio, United States, 44195 | |
| Austria | |
| Medical University of Vienna | |
| Vienna, Austria | |
| China | |
| Peking Union Medical College Hospital | |
| Beijing, China | |
| Germany | |
| University of Düsseldorf | |
| Düsseldorf, Germany, 40225 | |
| Ireland | |
| Mater Misericordiae Hospital | |
| Dublin, Ireland, 7 | |
| Singapore | |
| Tan Tock Seng Hospital | |
| Singapore, Singapore | |
| Principal Investigator: | Daniel I Sessler, MD | The Cleveland Clinic |
Documents provided by d sessler, The Cleveland Clinic:
| Responsible Party: | d sessler, Principal Investigator, The Cleveland Clinic |
| ClinicalTrials.gov Identifier: | NCT00418457 |
| Other Study ID Numbers: |
06-692 |
| First Posted: | January 4, 2007 Key Record Dates |
| Results First Posted: | June 16, 2020 |
| Last Update Posted: | June 16, 2020 |
| Last Verified: | June 2020 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
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Breast Cancer Anesthesia; regional cancer recurrence Anesthesia; inhalational Analgesia; opioid |
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Breast Neoplasms Recurrence Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Disease Attributes Pathologic Processes |
Anesthetics Propofol Central Nervous System Depressants Physiological Effects of Drugs Hypnotics and Sedatives Anesthetics, Intravenous Anesthetics, General |