Glioblastoma Multiforme (GBM)
GBM (Glioblastoma Multiforme) is typically challenging to cure, and there are currently no approved treatment modalities, resulting in a short life expectancy. Even with the best available treatments, most patients cannot survive beyond two years.
GBM is an abbreviation for Glioblastoma Multiforme, also known as malignant pleomorphic glioma.
It is one of the most common and aggressive brain tumors, often occurring in adults and the elderly.
GBM originates from glial cells in the brain, which are supportive cells that maintain neurons. Symptoms of GBM include headaches, seizures, cognitive impairment, and difficulties in speech and movement.
The treatment and research of GBM remain a focal point in neurology and oncology, with many institutions and research teams dedicated to finding more effective therapies and improving survival rates.
Background of Glioblastoma Multiforme (GBM)
- Lack of effective treatment: According to statistics from the American Cancer Society (ACS) and the Central Brain Tumor Registry of the United States (CBTRUS), an estimated 20,000 new brain tumor cases are diagnosed each year, with approximately 400 new cases of malignant gliomas in Taiwan annually. The current conventional therapies for treating malignant brain tumors, including surgical treatment, radiation therapy, and chemotherapy, have very limited efficacy, and there are no approved drugs, necessitating the development of new-generation therapies.
- Rapid recurrence and low survival rates: Glioblastoma Multiforme (GBM) can grow up to 16 times its size within one month and is a rapidly worsening primary brain tumor. The recurrence rate after surgery is also very high, often requiring patients to repeatedly undergo hospital treatments. Patients diagnosed with stage IV GBM have an average survival time of only 12 to 18 months. Malignant brain tumors spread rapidly and are challenging to eradicate. Once diagnosed, they are usually in advanced stages, and the average survival period is often around one year, with a 5-year survival rate of only 3.4%. The current standard treatment for malignant brain tumors involves a combination of surgery, radiation therapy, and chemotherapy, all of which have limited effectiveness.
- Several celebrities have encountered this unfortunate condition: Prominent individuals both domestically and internationally have died from incurable GBM, including U.S. Senators John Sidney McCain and Edward M. Kennedy, British politician Tessa Jowell, and New York Times journalist Tom Wicker.
- Diagnosis: The most common early symptom of brain tumors is headaches. Clinical symptoms may include headaches, increased intracranial pressure, double vision, and difficulty articulating thoughts, all of which may indicate a possible brain tumor. These symptoms are usually due to the tumor’s growth causing compression and edema in the brain tissues. Therefore, it is essential to be vigilant about any unusual bodily changes. If the above symptoms occur and worsen progressively, they may be related to GBM, making early detection challenging. In 2018, a woman named Mrs. Guo from Tzu Chi Hospital was diagnosed with GBM after experiencing sudden paralysis and collapsing due to dizziness.
Current Treatment Approaches for GBM
- Surgical Resection
Surgical resection is the preferred method for treating GBM. The goal of surgery is to remove the tumor as much as possible, reducing the burden of diseased cells and improving patient symptoms and quality of life. However, complete resection is challenging due to the invasive nature of GBM, and usually, only partial tumor removal is feasible. Surgical procedures carry high risks and may result in side effects and neurological damage.
- Radiation Therapy
Radiation therapy involves using high-energy gamma rays or other forms of radiation to destroy GBM tumor cells. External radiation is delivered from outside the body through machines that emit radiation beams directed at the affected area. The goal is to kill tumor cells effectively. Radiation therapy is a common approach for treating GBM, often used in combination with surgery. It may cause certain side effects, such as fatigue, nausea, vomiting, headaches, and skin redness.
Chemotherapy involves using chemical drugs to destroy GBM tumor cells. It can be administered alone or in combination with surgical resection and radiation therapy. Chemotherapy can be taken orally or intravenously, entering the bloodstream and reaching tumor cells to kill them. However, chemotherapy may also have toxic side effects on the body, such as hair loss, nausea, vomiting, and decreased immunity.
The core concept of immunotherapy is to harness the body’s immune system to attack and destroy brain tumor cells. Patients may receive certain medications that help rebuild or enhance their immune system, enabling it to more effectively target brain tumor cells.
Current Treatment Reference Drugs
Gliadel® Wafer (Carmustine Implant)
Gliadel® Wafer is an implantable treatment for GBM (Glioblastoma Multiforme). It is a biodegradable polymer-based circular wafer containing the chemotherapy drug Carmustine. Each wafer has a diameter of approximately 1.45 mm and a thickness of about 1 mm.
Gliadel® Wafer is used during brain tumor resection surgery. After the surgical procedure, the surgeon places the wafers at the site of tumor removal, with a maximum of 8 wafers allowed. Carmustine is released from the wafers and forms a high-concentration region around the remaining tumor, effectively killing the residual tumor cells, thereby extending the survival of GBM patients.
Clinical trials of Gliadel® Wafer have shown that the median overall survival for newly diagnosed patients was 13.8 months compared to 11.6 months in the placebo group. For recurrent patients, the median overall survival was 7.4 months with Gliadel Wafer compared to 5.5 months in the placebo group. (Source: Investigator’s Brochure)
Possible side effects may include seizures, brain edema, abnormal wound healing, and infections. Patients using Gliadel® Wafer need to be closely monitored for possible side effects.
Avastin® is a biopharmaceutical that contains the monoclonal antibody bevacizumab and is used for the treatment of brain tumors, including GBM.
The mechanism of action of Avastin® involves the inhibition of tumor angiogenesis, thereby slowing down or blocking tumor growth. It is used for the treatment of recurrent malignant gliomas (WHO Grade 4) – glioblastoma multiforme (GBM) in adult patients who have previously received standard radiation therapy and chemotherapy, including temozolomide, but the treatment has failed. (Source: Investigator’s Brochure)
Avastin® is administered intravenously, typically once every two weeks, until disease progression occurs. Common side effects of Avastin® include hypertension and bleeding.
Based on clinical trial data, the median overall survival for recurrent patients using Avastin® was 9.3 months, which is longer than the placebo group with 8.8 months.
TEMODAL has antitumor activity and is an alkylating agent containing the imidazotetrazine ring. In the systemic circulation, it rapidly undergoes chemical transformation to form the active compound MTIC (Monomethyl triazeno imidazole carboxamide) under physiological pH conditions. The theoretical cytotoxicity of MTIC is mainly attributed to its alkylation of the sixth oxygen atom of guanine, and it also undergoes minor additional alkylation at the seventh nitrogen atom of guanine, leading to subsequent cytotoxicity believed to be associated with these aberrantly repaired methylated compounds. (Source: Investigator’s Brochure)
TEMODAL is administered orally and is combined with radiation therapy. The treatment duration depends on the patient’s condition and may continue up to 2 years, typically ranging from 6 to 12 months. Side effects may include nausea, vomiting, and others.
Clinical trial data shows that the median overall survival for recurrent patients using TEMODAL was 5.8 months.
CEREBRACA® WAFER <Phase IIa> >>more
- Cerebraca® Wafer developed by Everfront Biotech Inc. is a therapeutic drug wafer that can be used to treat highly malignant glioblastoma (malignant brain cancer). It can be directly implanted into the brain and slowly releases drugs at a high concentration, high penetration, and long duration for about 1 month, exerting a multi-target effect that helps to treat cancer and make cancer cells more susceptible to chemotherapy or immune cell killing.
- Glioblastoma multiforme (GBM) is a highly malignant primary brain tumor that can grow up to 16 times its original size within a month. It has a high rate of recurrence after surgical resection, and there are currently no effective treatment options available.
- EF-API-001, the small molecule active pharmarceutical ingredient in Cerebraca® Wafer, has the following characteristics:
- Targeting Axl-1 receptor tyrosine kinase: effectively inhibits the growth and metastasis of brain tumor stem cells.
- Inhibiting the PD-L1 immune checkpoint: reduces the immune suppressive nature of the tumor microenvironment, thus preserving the activity of immune cells to kill tumor cells.
- Inhibition of MGMT DNA repair enzyme: overcomes resistance to Temozolomide (chemotherapy drug) and enables cancer cells to be killed again by chemotherapy.
- Cerebraca® Wafer, its small molecule active ingredient and biodegradable polymer are all manufactured by internationally renowned PIC/S GMP pharmaceutical companies in Taiwan to ensure high quality and reliable aseptic manufacturing processes.
AMG-193 <Phase II>
- AMG-193 is under clinical development by Amgen and currently in Phase II for Brain Tumor.
- AMG 193 is an MTA-cooperative PRMT5i that preferentially targets the MTA-bound state of PRMT5 that is enriched in MTAP-null tumors and represents a novel strategy to increase the therapeutic margin of this class of inhibitors.
PF-07799544 (ARRY-134) <Phase I>
- PF-07799544 (ARRY-134) is under development for the treatment of solid tumors by Pfizer including primary brain tumor and metastatic melanoma.
- It is administered through oral route in the form of tablet.
GBM Recovery: Living Care and Precautions
During the GBM recovery period, it is essential to have sufficient rest and sleep to aid in cell repair, enhance the immune system, and reduce fatigue. If in the advanced stages of brain cancer, as the tumor continues to grow, symptoms like headaches, dizziness, memory loss, weakness, and seizures may arise, making adequate rest even more crucial to maintain physical strength.
A well-balanced diet can assist in body restoration and improve physical strength. It is advisable to consume fresh vegetables and fruits while reducing the intake of high-fat, high-sugar, and processed foods. It is essential to follow the physician’s advice for a balanced diet.
Engaging in light exercises such as walking, yoga, or tai chi during the recovery period can help in physical rehabilitation, alleviate fatigue, and boost immunity.
Adherence to Medication and Prescription Instructions
Proper and timely administration of medication, as instructed by the doctor, is crucial in treating GBM. During medication therapy, regular follow-ups and check-ups are necessary to enable doctors to make timely adjustments to the treatment plan.
Psychological or Spiritual Therapy
Both GBM patients and their family members often experience significant emotional stress and pressure. Psychological or spiritual therapy can help relieve stress, enabling patients and families to face the disease more positively and maintain a better quality of life.
Patients undergoing hospital or home-based GBM recovery must pay special attention to safety measures and precautions. Monitoring the living environment and taking steps to prevent falls and other accidents are essential for patient safety.