Glioblastoma multiforme medical therapy
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Medical Treatment
Treatment of primary brain tumors and brain metastases consists of both symptomatic and palliative therapies.
Symptomatic therapy
Supportive treatment focuses on relieving symptoms and improving the patient’s neurologic function. The primary supportive agents are anticonvulsants and corticosteroids.
- Anticonvulsants are administered to the ~25% of patients who have a seizure. Prospective studies have failed to show the efficacy for prophylactic anticonvulsants. Those receiving phenytoin concurrent with radiation may have serious skin reactions such as erythema multiforme and Stevens-Johnson syndrome.
- Corticosteroids, usually dexamethasone given 4 to 10 mg every 4 to 6 h, can reduce peritumoral edema (through rearrangement of the blood-brain barrier), diminishing mass effect and lowering intracranial pressure, with a decrease in headache or drowsiness.
Palliative therapy
Palliative treatment usually is done to achieve a longer survival time, albeit only a slight increase [see below]. It includes surgery, radiation therapy, and chemotherapy.
A maximally feasible resection with maximal tumor-free margins ("debulking") is usually performed along with external beam radiation and chemotherapy. Total cranial irradiation (4500 cGy) with a boosted dose (1500 to 2000 cGy) at the site of the tumor can increase survival by 5 months [see below]. The addition of the chemotherapeutic agent carmustine (BiCNU) alone increases survival slightly. Most oncologists prefer a combination chemotherapy consisting of procarbazine, lomustine, and vincristine (PCV regimen). Another combination includes carboplatin and cisplatin. Their efficacy is limited, and toxicity, particularly with the PCV regimen, can be considerable. Despite initial studies suggesting the superiority of PCV over BiCNU, there are now clear data demonstrating no benefit of PCV over BiCNU in either glioblastoma or anaplastic astrocytoma patients. Brachytherapy (implantation of radioactive beads or needles) and high-dose focus radiotherapy (stereotactic radiosurgery) have not shown to increase survival times.
In a large phase III trial, implantation of BiCNU-impregnated wafers - trade name Gliadel Wafers - at the time of primary resection, improved median survival to 13.9 months, compared with only 11.6 months for placebo wafers (P = .03), in newly-diagnosed patients with malignant glioma.[1] Despite initial treatment, virtually all malignant gliomas recur. At relapse, patients may benefit from re-resection, focal radiotherapy techniques (such as radiosurgery), and different chemotherapeutic agents. Depending upon which chemotherapeutic agent was used at initial treatment, temozolomide, procarbazine, or a nitrosourea would be a reasonable conventional choice at recurrence. Clinical trials employing signal transduction inhibitors, epidermal growth factor receptor inhibitors, or antiangiogenic agents may also be available at tumor relapse.
The use of temozolomide alongside radiotherapy has shown survival benefit,[2] and is currently considered the standard of care by the National Cancer Institute.[3]
In recent studies, the antimalarial drug chloroquine has been shown to increase mid-term survival when given in combination with conventional therapy.[4][5][6] Further research in this area needs to be done.
Another possible therapy technique is to use viruses to attack the cancer.[7]
A recent paper titled reported on the treatment of glioblastoma multiforme with photodynamic therapy at Melbourne Royal Infirmary, Australia since 1986.[8] Five year survival rates were over 30% with some patients surviving over 10 years.
Yet another recent - but still experimental - therapy approach is the treatment using nanoparticles. [9] These consist of an iron oxide core as well as a cover facilitating the infiltration of the particles into the cancer cells. The particles are injected directly into the tumor. The tumor enriched with the iron oxide particles is then repeatedly warmed via alternating magnetic fields to above 46 degrees Celsius. In animal models, considerably-improved survival terms arose[10]; however, at present there are not any results from efficacy studies in man yet, but results are expected to be published later this year.
References
- ↑ Westphal M, Hilt DC, Bortey E; et al. (2003). "A phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma". Neuro-oncology. 5 (2): 79–88. doi:10.1215/S1522-8517-02-00023-6. PMID 12672279.
- ↑ Stupp R, Mason WP, van den Bent MJ; et al. (2005). "Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma". N. Engl. J. Med. 352 (10): 987–96. doi:10.1056/NEJMoa043330. PMID 15758009.
- ↑ "Temozolomide Plus Radiation Helps Brain Cancer - National Cancer Institute". Retrieved 2007-09-15.
- ↑ Sotelo J, Briceño E, López-González MA (2006). "Adding chloroquine to conventional treatment for glioblastoma multiforme: a randomized, double-blind, placebo-controlled trial". Ann. Intern. Med. 144 (5): 337–43. PMID 16520474.
- ↑ Toler SM, Noe D, Sharma A (2006). "Selective enhancement of cellular oxidative stress by chloroquine: implications for the treatment of glioblastoma multiforme". Neurosurgical focus. 21 (6): E10. PMID 17341043.
- ↑ Briceño E, Calderon A, Sotelo J (2007). "Institutional experience with chloroquine as an adjuvant to the therapy for glioblastoma multiforme". Surgical neurology. 67 (4): 388–91. doi:10.1016/j.surneu.2006.08.080. PMID 17350410.
- ↑ Hoffmann D, Wildner O (2007). "Comparison of herpes simplex virus- and conditionally replicative adenovirus-based vectors for glioblastoma treatment". Cancer Gene Ther. 14 (7): 627–39. doi:10.1038/sj.cgt.7701055. PMID 17479104.
- ↑ Stylli SS, Kaye AH, MacGregor L, Howes M, Rajendra P (2005). "Photodynamic therapy of high grade glioma - long term survival". Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia. 12 (4): 389–98. doi:10.1016/j.jocn.2005.01.006. PMID 15925768.
- ↑ Maier-Hauff et al.: Intracranial thermotherapy using magnetic nanoparticles combined with external beam radiotherapy: results of a feasibility study on patients with glioblastoma multiforme. J Neurooncol. 2007 Jan;81(1):53-60. PMID 16773216
- ↑ Jordan et al.:The effect of thermotherapy using magnetic nanoparticles on rat malignant glioma. J Neurooncol. 2006 May;78(1):7-14. PMID 16314937