Trial Summary
What is the purpose of this trial?Cancer is a leading cause of death worldwide. It is estimated that approximately 55,000 Canadians are surviving with brain tumors. It is projected that around 3000 persons will be diagnosed with brain and spinal cord tumors, and approximately 75 percent patients will not survive. Out of all brain cancers, high-grade gliomas \[Glioblastoma Multiforme (GBM)\] impose highest morbidity and mortality. Therefore, it is important to explore ways in which Investigators can improve and prolong the lives of patients suffering from brain cancers, particularly high-grade glioma, which is the most common and aggressive primary brain tumor.
So far the Investigators know that the surgery, chemotherapy and radiotherapy are the three corner stones management options for these patients, and majority of the research have been conducted on these three major domains. Therefore, it is imperative to explore the other variables those may impact survival characteristics. One of the integral variables of the brain cancer surgery is anesthesia. Interestingly, the role of anesthetics was explored in some other non-brain solid organ tumor surgeries. It is observed that out of the two main types of anesthesia \[one is through intravenous (propofol) and other one is gaseous (sevoflurane)\], intravenous based anesthesia maintenance regime may delay the cancer progression and prolong the recurrence free period. In addition, two very large retrospective studies with approximately 11,000 and 18,000 patients respectively, showed that as compared to gaseous (volatile anesthetics) based, intravenous (propofol) based anesthesia conferred some protection against cancer progression and was also associated with lesser overall mortality. The exact nature of these protective mechanisms is not known but in animal and other laboratory-based experiments, propofol seems to inhibit cancer formation steps, delays inflammation and provide protection from cancer cell growth. This is a feasibility study for knowing various aspects of workflow; recruitment characteristics of participants and various obstacles in implying anesthesia based protocols so that the Investigators can conduct a well-designed multicenter international randomized study.
Is the drug Propofol or Sevoflurane a promising treatment for brain cancer survival?The provided research articles do not discuss Propofol or Sevoflurane in the context of brain cancer survival. They focus on treatments like stereotactic radiosurgery and Gamma Knife surgery for acoustic tumors, which are different from brain cancer. Therefore, there is no information here to suggest that Propofol or Sevoflurane is a promising treatment for brain cancer survival.34589
What safety data exists for anesthesia types used in brain cancer treatment?The provided research does not contain specific safety data for anesthesia types like Propofol or Sevoflurane in brain cancer treatment. The studies focus on other drugs and treatments, such as carboplatin, sodium valproate, cisplatin, etoposide, VP 16-213, and patupilone, none of which are related to the anesthesia types in question.126713
Do I need to stop my current medications for this trial?The trial protocol does not specify if you need to stop your current medications. However, since this is a feasibility study for anesthesia in brain cancer surgery, it's best to discuss your medications with the trial team.
What data supports the idea that Anesthesia Type for Brain Cancer Survival is an effective treatment?The available research shows that the effectiveness of the anesthesia type for brain cancer survival, specifically using propofol, is not clearly established. Studies have looked at propofol compared to other anesthetics like sevoflurane in different types of cancer surgeries, such as breast and lung cancer. Some studies suggest that propofol might have a slight advantage in improving long-term survival in these cases, but the results are not consistent or conclusive. Therefore, while there is some indication that propofol could be beneficial, more research is needed to confirm its effectiveness specifically for brain cancer survival.1011121415
Eligibility Criteria
This trial is for adults over 18 years old who are scheduled for their first surgery to remove a high-grade brain tumor using general anesthesia. It's not open to children, pregnant women, those with recurrent GBM, severe adrenal problems, low-grade tumors or conditions that prevent post-op MRI.Inclusion Criteria
I am scheduled for an elective procedure between July 1, 2022, and December 28, 2023.
I am scheduled for a surgery to remove a suspected severe brain tumor.
Exclusion Criteria
I am scheduled for or have had an awake brain surgery.
I am not pregnant and not a child.
I have been diagnosed with severe adrenal gland problems.
I am suspected to have a low-grade brain tumor or non-glial brain tumor.
I can safely undergo an MRI after surgery.
My brain cancer has come back.
My surgery requires special monitoring that affects anesthesia choice.
Treatment Details
The study compares two types of anesthesia in brain cancer surgery: Propofol (intravenous) and Sevoflurane (gaseous). The goal is to see if one can better prolong life by delaying cancer progression based on previous findings suggesting Propofol might be more protective.
2Treatment groups
Experimental Treatment
Active Control
Group I: Propofol groupExperimental Treatment1 Intervention
20 patients scheduled for the elective craniotomy for suspected high-grade gliomas resection will be enrolled and further randomized to receive total intravenous anesthesia (propofol group). Standard fasting and monitoring guidelines will be instituted. All patients will be induced and intubated after administration of intravenous boluses of fentanyl, propofol and rocuronium. For the maintenance phase of anesthesia, patients in the propofol group will receive continuous infusions of propofol and remifentanil. No patients will receive nitrous oxide.
Group II: Sevoflurane groupActive Control1 Intervention
20 patients scheduled for the elective craniotomy for suspected high-grade gliomas resection will be enrolled and further randomized to receive Volatile (sevoflurane group) agent for the maintenance phase of anesthesia. Standard fasting and monitoring guidelines will be instituted. All patients will be induced and intubated after administration of intravenous boluses of fentanyl, propofol and rocuronium. For the maintenance phase of anesthesia, patients in the volatile inhalational anesthesia group will received a volatile inhalational agent (sevoflurane) and remifentanil infusion. No patients will receive nitrous oxide.
Propofol group is already approved in United States, European Union, Canada for the following indications:
🇺🇸 Approved in United States as Diprivan for:
- Induction and maintenance of general anesthesia or sedation
🇪🇺 Approved in European Union as Propofol-Lipuro for:
- Induction and maintenance of general anesthesia or sedation
🇨🇦 Approved in Canada as Propoven for:
- Induction and maintenance of general anesthesia or sedation
Find a clinic near you
Research locations nearbySelect from list below to view details:
Toronto Western Hospital/UHNToronto, Canada
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Who is running the clinical trial?
University Health Network, TorontoLead Sponsor
References
[Therapeutic experiences using the new podophyllotoxin derivative VP 16-213 in malignant human tumors]. [2013]The new semisynthetic epipodophyllotoxin VP 16-213 has been tested for antitumor activity and toxicity in a non-randomized phase II trial. The study included 33 patients with solid tumors and acute leukemias. The drug was given in 5-day courses every 3 weeks, parenterally for the first 2 courses and thereafter orally. Subjectively VP 16-213 was well tolerated in both i.v. and oral administration, but almost universally induced leukothrombopenia and hair loss. The best results were achieved in 12 patients with oat cell carcinoma of the lung (4 good and 4 less good responses). Remissions of lesser quality were also observed in anaplastic lung cancer, ovarian carcinoma and acute myelomonocytic leukemia. VP 16-213 possesses proven, clinically valuable cytostatic activity against various human neoplasms. Complementary studies to establish its optimum dosage and administration, and its place in combination chemotherapy, are in progress.
Pharmacology of intrathecal VP-16-213 in dogs. [2019]VP-16-213 is an anticancer drug that is active against a number of malignancies including small cell lung cancer, lymphoma, and leukemia which are often complicated by the development of leptomeningeal carcinomatosis. To investigate the potential usefulness of VP-16-213 for intrathecal administration, the pharmacology and toxicity of intrathecal VP-16-213 was determined. VP-16-213 at varying doses (0.01-1.0 mg.kg) was instilled intrathecally in dogs. Plasma, CSF, spinal cord, and brain tissue drug concentrations were determined by radiochemical and high performance liquid chromatography technique. Drug concentrations were strikingly higher in spinal cord tissue near the injection site compared to more distal cord sites. CSF concentration of VP-16-213 is 3-4 logs higher compared to concurrent plasma levels. Severe neurotoxicity occurred at the higher doses used. Due to limited diffusion and extremely low doses which could be used without life-threatening neurotoxicity, VP-16-213 does not appear to be a useful agent for intrathecal administration.
Stereotactic radiosurgery in the treatment of patients with acoustic tumors. [2021]Stereotactic radiosurgery is performed under local anesthesia, and most patients can be discharged from the hospital within 24 hours of treatment. All patients in our series returned to their preoperative level of employment or function within 5 to 7 days of treatment, and this functional level was maintained over the period of follow-up. "Tumor control" was achieved in 96% of patients during an average follow-up of 1.7 years. Tumor shrinkage occurred in 45% of patients who had at least 1.5 years of follow-up. Useful hearing preservation rates were 50% at 6 months and 30% 1 year after treatment. New delayed facial or trigeminal neuropathy occurred in 34% and 32% of patients, respectively, with a median onset of 5 to 6 months after treatment. The vast majority of cranial neuropathies were partial at onset and tended to improve over time. Other complications included tumor growth (4%), communicating hydrocephalus (4%), and transient adjacent brain parenchymal changes best seen on T2-weighted MRI (9%). Stereotactic radiosurgery is an important alternative treatment for carefully selected patients with acoustic tumors. Indications for treatment include sufficient medical problems to pose excessive surgical risk, advanced age, the presence of bilateral acoustic tumors or contralateral deafness, recurrent tumor despite surgical resection, or refusal to undergo microsurgery. Radiosurgery is contraindicated in patients with symptomatic brain stem or cerebellar compression from a large acoustic tumor. Previous posterior fossa radiotherapy is a relative contraindication that must be considered on a patient to patient basis. Stereotactic radiosurgery should be viewed as an additional weapon in our arsenal for combating acoustic tumors rather than feared as a potential replacement for surgical excision. The strategic role of stereotactic radiosurgery in the overall treatment of patients with acoustic tumors will continue to be refined as longer-term, carefully assessed results become available.
Stereotactic radiosurgery for acoustic tumors. [2004]Stereotactic radiosurgery is an important alternative treatment for carefully selected patients with acoustic tumors. We perform radiosurgery under local anesthesia, and 91% of our patients have been discharged from the hospital within 24 hours after treatment. All returned to their preoperative level of function or employment within 5 to 7 days after treatment. Our current tumor control rate is 97%, but reduction in tumor size, judged by strict, objective criteria, was achieved in only 23%. Our actuarial rate of useful hearing preservation after radiosurgery is 38% at 1 year. Three tumors increased in size after treatment. Only one of the three demonstrated increased mass effect on surrounding brain structures by neuroimaging criteria. No increase has led to worsened clinical symptoms or has required surgical excision at this point in follow-up. The 1-year rates for developing new facial or trigeminal neuropathies after radiosurgery were 30% and 33%, respectively. Cranial neuropathies had a delayed onset, with the median onset occurring after 5 to 6 months. The vast majority were partial at onset, and most improved over time. Communicating hydrocephalus requiring ventriculoperitoneal shunts developed after radiosurgery in four patients. Eight patients developed increased signal within adjacent brain parenchyma on T2-weighted MR imaging, consistent with edema or blood-brain barrier breakdown. It is unlikely that stereotactic radiosurgery using the gamma knife will obviate the need for microsurgical removal performed by skilled and experienced microsurgeons. However, radiosurgery is a safe and effective treatment for patients whose medical problems make surgery unacceptably dangerous, those with bilateral tumors or a tumor in their only hearing ear, those who have recurrent tumor despite surgical resection, or patients who refuse microsurgical excision.
Gamma knife: an alternative treatment for acoustic neurinomas. [2017]Despite surgical advances and technologic means of better monitoring seventh and eighth nerve function intraoperatively, there remains a group of patients for whom alternative methods of treatment are desirable. These include the elderly, those with bilateral tumors or tumors in only hearing ears, individuals with medical contraindications to major surgery, and those who refuse surgical resection. The University of Pittsburgh became the fifth world center and the first in the United States to install the "gamma knife" for stereotactic radiosurgery. On the basis of the pioneering work done at the Karolinska Institute in Stockholm, acoustic tumor patients who fulfill the above criteria are being treated. A tumoricidal single treatment closed-skull radiation dose is given through 201 sharply focused cobalt 60 sources, minimizing the effects on surrounding brain or other tissues. Our early results are discussed and compared to those from more than 200 cases in Stockholm. Complications and expected long-term results are presented.
Cisplatin and etoposide combination in the treatment of bronchogenic carcinoma. [2013]The authors investigated the activity of a combination of DDP 80 mg/m2 i.v. followed by VP16 50 mg/m2 on days 2-5 in bronchogenic carcinoma. Twenty-seven patients entered the study (10 small cell carcinoma, 9 squamous cell, 2 adenocarcinomas and 6 histologically undefined). Six patients evidenced partial response (22.3%); one patient (small cell) had complete remission. The toxicity of the regimen was scarce and well-tolerated by patients with an incidence of 88.8% alopecia, and 77.7% nausea and/or vomiting.
Multicenter phase 2 study of patupilone for recurrent or progressive brain metastases from non-small cell lung cancer. [2018]Treatment options for patients with non-small cell lung cancer (NSCLC) with brain metastases are limited. Patupilone (EPO906), a blood-brain barrier-penetrating, microtubule-targeting, cytotoxic agent, has shown clinical activity in phase 1/2 studies in patients with NSCLC. This study evaluates the efficacy, pharmacokinetics, and safety of patupilone in NSCLC brain metastases.
Repeat Gamma Knife surgery for vestibular schwannomas. [2020]Gamma Knife (GK) surgery is a recognized treatment option for the management of small to medium-sized vestibular schwannoma (VS) associated with high-tumor control and low morbidity. When a radiosurgical treatment fails to stop tumor growth, repeat GK surgery can be proposed in selected cases.
Early Nerve Grafting for Facial Paralysis After Cerebellopontine Angle Tumor Resection With Preserved Facial Nerve Continuity. [2022]Preserving facial nerve function is a primary goal and a key decision factor in the comprehensive management of vestibular schwannoma and other cerebellopontine angle (CPA) tumors.
Retrospective analysis of 1-year mortality after gastric cancer surgery: Total intravenous anesthesia versus volatile anesthesia. [2020]It remains controversial whether propofol-based total intravenous anesthesia (TIVA) or inhalation anesthesia is associated with better outcomes after cancer surgery. We investigated whether there is a difference in the 1-year overall or cancer-related mortality between propofol-based TIVA and inhalation anesthesia in patients who underwent gastric cancer surgery.
Survival after primary breast cancer surgery following propofol or sevoflurane general anesthesia-A retrospective, multicenter, database analysis of 6305 Swedish patients. [2021]Retrospective studies indicate that the choice of anesthetic can affect long-term cancer survival. Propofol seems to have an advantage over sevoflurane. However, this is questioned for breast cancer. We gathered a large cohort of breast cancer surgery patients from seven Swedish hospitals and hypothesized that general anesthesia with propofol would be superior to sevoflurane anesthesia regarding long-term breast cancer survival.
Anesthesia and Long-term Oncological Outcomes: A Systematic Review and Meta-analysis. [2023]Whether propofol elicits a survival benefit over volatile anesthetics during cancer surgery remains inconclusive. The primary aim of this systematic review and meta-analysis is to compare the effects of propofol-based total intravenous anesthesia (TIVA) with any volatile anesthesia on long-term oncological outcomes. The secondary aim is to compare propofol-based TIVA with specific volatile agents on long-term oncological outcomes.
Clinical experience of convection-enhanced delivery (CED) of carboplatin and sodium valproate into the pons for the treatment of diffuse intrinsic pontine glioma (DIPG) in children and young adults after radiotherapy. [2021]Effective treatment of diffuse intrinsic pontine glioma (DIPG) remains a formidable challenge due to inadequate penetration of the blood-brain barrier (BBB) by systemically administered chemotherapies. The BBB can be overcome by directly infusing drugs into pons using method of convection-enhanced delivery (CED). We describe our clinical experience and what we have learned about the safety and feasibility of treating DIPG with intermittent CED of carboplatin and sodium valproate to the pons through the Renishaw Drug Delivery System (RDDS).
Effect of total intravenous versus inhalation anesthesia on long-term oncological outcomes in patients undergoing curative resection for early-stage non-small cell lung cancer: a retrospective cohort study. [2023]Propofol-based total intravenous anesthesia (TIVA) improves long-term outcomes after cancer surgery compared with inhalation anesthesia. However, its effect on patients undergoing non-small cell lung cancer (NSCLC) surgery remains unclear. We aimed to compare the oncological outcomes of TIVA and inhalation anesthesia after curative resection of early-stage NSCLC.
Impact of general anaesthesia on breast cancer survival: a 5-year follow up of a pragmatic, randomised, controlled trial, the CAN-study, comparing propofol and sevoflurane. [2023]Anaesthesia may impact long-term cancer survival. In the Cancer and Anaesthesia study, we hypothesised that the hypnotic drug propofol will have an advantage of at least five percentage points in five-year survival over the inhalational anaesthetic sevoflurane for breast cancer surgery.