Glioblastoma multiforme medical therapy

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. 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, and is currently considered the standard of care by the National Cancer Institute.

In recent studies, the antimalarial drug chloroquine has been shown to increase mid-term survival when given in combination with conventional therapy. Further research in this area needs to be done.

Another possible therapy technique is to use viruses to attack the cancer.

A recent paper titled reported on the treatment of glioblastoma multiforme with photodynamic therapy at Melbourne Royal Infirmary, Australia since 1986. 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. 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 ; however, at present there are not any results from efficacy studies in man yet, but results are expected to be published later this year.

Recurrences
Tumor recurrence after surgery or radiation is almost inevitable, usually within 2 cm of the original site, and 10% may develop new lesions at distant sites. Reoperation or brachytherapy has been attempted, with uncertain results. The most aggressive therapy, a second surgery and chemotherapy, is, in general, used in those under 40 years of age whose original operation was many months earlier. If the PCV regimen has not been used, it may be tried; else, the newer agent temozolomide may be used. However, these regimens usually only increase the symptom-free interval, rather than prolong survival.