Malignant astrocytomas medical therapy

Prophylactic treatment
Patients with seizures should be treated, but prophylactic treatment of patients solely with tumors has not been validated. Patients with brain tumors have a reported increase in adverse drug reactions, including Stevens-Johnson syndrome. It is thought that the combination of steroid therapy, radiation and phenytoin predispose to this adverse outcome.

Glucocorticoids
Glucocorticoids (dexamethasone 4mg QID) can help relieve symptoms associated with increased ICP. The dose can be increased on a PRN basis. The dose is generally tapered after resection and continued at a low dose during adjunctive radiation therapy and eventually discontinued prior to chemotherapy.

Unstable patients
Temporizing measures for unstable patients with increased ICP include intubation, hyperventilation, IV mannitol, and VP shunt placement. It should be noted that the usefulness of hyperventilation and mannitol diminishes with time, and these measures should be used as a bridge to definitive therapy.

Radiation therapy
Radiation therapy is used in symptomatic and for unresectable/partially resectable Grade I-II astrocytoma. Adjuvant radiation therapy increased survival from a median 14 to 36 weeks in high-grade astrocytoma. Radiation therapy originally consisted of whole brain irradiation because of the infiltrative nature of the high-grade tumors. Survival seemed to correlate with increasing dose of radiation administered, but was limited by the adverse sequelae of blood vessel injury, demyelination of the white matter and radiation necrosis.

Focal external beam radiation
Focal external beam radiation limits the field exposed and is thought to be sufficient since 80-90% of recurrences occur within 2 cm of the primary site. This technique is associated with fewer adverse events and similar recurrence rates. PET imaging has been used to help predict recurrence and to differentiate between radiation necrosis and recurrent tumor.

Development of new radiation techniques is ongoing. Brachytherapy is in use, but is limited by technical difficulty in placing the radioactive seeds and does not seem to be more effective than adjuvant chemotherapy. Stereotaxic radiosurgery’s (gamma knife) role is uncertain. Heavy particle radiation therapy (neutrons, charged helium or neon) is limited by unproven efficacy and the lack of widely available, inexpensive nuclear reactors.

Chemotherapy
Chemotherapy is not used in low-grade astrocytoma. Adjuvant chemotherapy with nitrosurea (BCNU) or procarbazine adds a modest survival benefit (18 month survival 19% versus 4%) in high-grade astrocytoma. With possibly the exception of temozolomide (TMZ), chemotherapy alone has not shown a mortality benefit, though response rates of 40% for 26 to 30 weeks have been reported for a variety of single and multiple-drug regimens. TMZ is approved for in relapsed Grade III astrocytoma only, not Grade IV.

Current work is underway looking at high dose IV chemotherapy with nitrosureas with autologous stem cell rescue and intraarterial delivery of chemotherapeutics and monoclonal antibodies ± disruption of the blood-brain barrier.