Regional Anesthesia and Breast Cancer Recurrence

Breast Neoplasms Clinical Trial

Official title:

Regional Anesthesia and Breast Cancer Recurrence

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00418457
• Other study ID #: 06-692
• Status: Completed
• Phase: Phase 3
• Start date: January 2007
• Est. completion date: December 2019

Study information

• Verified date: June 2020
• Source: The Cleveland Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In this multi-center trial, Stage 1-3 patients having mastectomies or isolated lumpectomy with axillary node dissection will be randomly assigned to thoracic epidural or paravertebral anesthesia/analgesia, or to general anesthesia and morphine analgesia. Participants will be followed for up to 10 years to determine the rate of cancer recurrence or metastasis.

Description:

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:

1. 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.

2. Anesthesia impairs numerous immune functions, including those of neutrophils, macrophages, dendritic cells, T-cell, and natural killer cells.

3. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2108
• Est. completion date: December 2019
• Est. primary completion date: February 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms
• Recurrence

Intervention

Drug:
• General anesthesia and opioids
General anesthesia, usually with sevoflurane, and opioid analgesia
• Regional analgesia and propofol
Regional anesthesia and analgesia (either epidural or paravertebral), combined with deep sedation or general anesthesia

Locations

Country	Name	City	State
Austria	Medical University of Vienna	Vienna
China	Peking Union Medical College Hospital	Beijing
Germany	University of Düsseldorf	Düsseldorf
Ireland	Mater Misericordiae Hospital	Dublin
Singapore	Tan Tock Seng Hospital	Singapore
United States	Cleveland Clinic Foundation	Cleveland	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
The Cleveland Clinic

Countries where clinical trial is conducted

United States,  Austria,  China,  Germany,  Ireland,  Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Who Had Breast Cancer Recurrence After Breast Cancer Surgery	time to breast cancer recurrence from the end of surgery.	up to 10 years
Secondary	Number of Participants That Experienced Post-Surgical Pain	Brief Pain Inventory is used to evaluate with values of any pain vs. no pain (binary)	6 months and 1 year
Secondary	Number of Participants That Experienced Neuropathic Pain After Surgery	neuropathic pain is a binary outcome: any pain vs. no pain	6 month and 1 year
Secondary	SF-12 PCS Score	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.	6 month and 1 year
Secondary	SF-12 MCS Score	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.	6 month and 1 year

External Links

•   Can regional analgesia reduce the risk of recurrence after breast cancer? Methodology of a multicenter randomized trial. Author: Daniel I Sessler Contemporary Clinical Trials, Volume 29, Issue 4, July 2008, Pages 517-526