Glioblastoma multiforme medical therapy: Difference between revisions
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*Methylation of MGMT is found in 30–60% of GBM cases and is associated with a favorable outcome if treated with alkylating agents. | *Methylation of MGMT is found in 30–60% of GBM cases and is associated with a favorable outcome if treated with alkylating agents. | ||
*There is evidence that glioma stem cells contribute to GBM chemoresistance. | *There is evidence that glioma stem cells contribute to GBM chemoresistance. | ||
*Stem cells from highly chemotherapy resistant grade IV gliomas show expression of multidrug resistance protein-1 (MRP1) transporters and grade II gliomas show expression of P-glycoprotein | |||
===Supportive treatment=== | ===Supportive treatment=== | ||
Revision as of 15:06, 25 March 2019
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Marjan Khan M.B.B.S.[2]
Overview
The predominant therapy for glioblastoma multiforme is surgical resection. Adjunctive chemotherapy and radiation may be required.[1][2][3] Supportive therapy for glioblastoma multiforme includes anticonvulsants and corticosteroids.Cytotoxic therapy for GBM has evolved due to the approval of temozolomide,an alkylating agent- for newly diagnosed GBM. Active agents include also the nitrosureas which include carmustine and lomustine, platinum agents, etoposide, irinotecan and PCV combination.
Medical Therapy
- The predominant therapy for glioblastoma multiforme is surgical resection. Adjunctive chemotherapy and radiation may be required.[1][2][3]
- Cytotoxic therapy for GBM has evolved due to the approval of temozolomide which is an alkylating agent.
- Active agents include also the nitrosureas that include carmustine (BCNU) and lomustine (CCNU), platinum agents, etoposide, irinotecan and PCV combination.
- Temozolomide is a newer oral alkylating agent that has excellent penetration into the central nervous system.
- Temozolomide has 96-100% bioavailability and promotes the methylation of the O6 position on guanine.
- Temozolomide can be effective for recurrent GBM while its efficacy can be increased with metronomic rather than standard schedule as well as with high average daily dose (>100 mg/m2).
- The nitrosureas, carmustine (1,2 bis[2-chloreoethyl]-1-nitrosurea BCNU) and lomustine (CCNU), are two alkylating drugs used in the treatment of GBM.
- Carmustine biodegradable wafers (Gliadel) are an implantable depot form of BCNU that are placed in the cavity that is formed after resection of newly diagnosed or recurrent tumor.
Radiotherapy
- Post-operative radiotherapy is recommended among all patients who develop glioblastoma multiforme.
- Adjuvant radiotherapy can reduce the tumor size to 107 cells.
- Radiotherapy may not cure the cancer, but can control the tumor and delay recurrence.
- Targeted three-dimensional conformal radiotherapy is preferred to whole brain radiotherapy.
- Total radiation dose of 5,000-6,000 cGy has been found to be optimal for treatment.[2]
Chemotherapy
- Chemotherapy is indicated as adjuvant therapy for glioblastoma multiforme.[3]
- Temozolomide (Temodar) is the preferred drug for the treatment of glioblastoma multiforme.[3]
- Irinotecan, etoposide and cisplatin have been used in the treatment of GBM demonstrating modest efficacy as adjuvant chemotherapy.
- Other chemotherapeutic drugs that may be used for the treatment of glioblastoma multiforme include:
Resistance to chemotherapy and radiotherapy
- Many GBMs have intrinsic or acquired resistance to chemotherapy.
- MGMT gene promoter methylation is an important mechanism of resistance to temozolomide treatment in GBM.
- Methylation of MGMT is found in 30–60% of GBM cases and is associated with a favorable outcome if treated with alkylating agents.
- There is evidence that glioma stem cells contribute to GBM chemoresistance.
- Stem cells from highly chemotherapy resistant grade IV gliomas show expression of multidrug resistance protein-1 (MRP1) transporters and grade II gliomas show expression of P-glycoprotein
Supportive treatment
Supportive therapy for glioblastoma multiforme includes anticonvulsants and corticosteroids, which focuses on relieving symptoms and improving the patient’s neurologic function.
- Anticonvulsants are administered to the patients who have a seizure. Phenytoin given concurrently with radiation may have serious skin reactions such as erythema multiforme and Stevens-Johnson syndrome.
- Corticosteroids, usually dexamethasone given 4-10 mg every 4-6 h, can reduce peritumoral edema, diminish mass effect, and lower intracranial pressure with a decrease in headache or drowsiness.
References
- ↑ 1.0 1.1 Treatment of glioblastoma multiforme. Dr Dylan Kurda and Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/glioblastoma
- ↑ 2.0 2.1 2.2 Barani IJ, Larson DA (2015). "Radiation therapy of glioblastoma". Cancer Treat Res. 163: 49–73. doi:10.1007/978-3-319-12048-5_4. PMID 25468225.
- ↑ 3.0 3.1 3.2 3.3 Minniti G, Muni R, Lanzetta G, Marchetti P, Enrici RM (2009). "Chemotherapy for glioblastoma: current treatment and future perspectives for cytotoxic and targeted agents". Anticancer Res. 29 (12): 5171–84. PMID 20044633.