Ccnu

Vincristinea

Cisplatin

Temozolomide Temozolomide

Vincristine6 Cyclophosphamide Cisplatin Etoposide

100 mg/m2 PO, day 1 1.5 mg/m2 IV, days 1, 8 40 mg/m2 PO, days 1-14 OR

100 mg/m2 PO, day 1 1.5 mg/m2 IV, days 1, 8 100 mg/m2 PO, days 1-14 OR

75 mg/m2 PO, day 1 1.5 mg/m2 IV, days 1, 8, 14 75 mg/m2 IV, day 1 over 6 hours OR

90 mg/m2/day PO x 42 days 150-200 mg/m2/day PO x 5 days OR

0.065 mg/kg IV, days 1, 8, 29, 36 65 mg/kg IV, days 1, 29 4 mg/kg IV over 6 hours, day 57 6.5 mg/kg IV over 1 hour, days 59, 60

Every 6 weeks for 8 cycles

Every 6 weeks for 8 cycles

Every 6 weeks for 8 cycles

During radiation therapy Every 28 days for 6-12 cycles

Every 12 weeks for 4 cycles for children ages 24-36 months For children less than 24 months of age at diagnosis for 8 cycles

"Maximum dose 2 mg. •"Maximum dose 1.5 mg.

• Glioblastoma multiforme demonstrates increased nuclear anaplasia, pseudopal-isading, and multinucleate giant cells (WHO grade IV).

The majority of cerebellar astrocytomas remain confined to the cerebellum. Very rarely do they have neuraxis dissemination.

Low-Grade Astrocytomas

Low-grade astrocytomas present with hydrocephalus, focal signs, or seizures. Surgery

Surgical excision is the initial treatment. Gross total resection is desirable. Pilocytic astrocytomas are slow growing and well circumscribed with a distinct margin. These features permit complete resection in 90% of patients with posterior fossa tumors, and a majority of hemispheric tumors. By contrast, diffuse low-grade astrocytomas are infiltrative and are less often completely resected. Diencephalic tumors are amenable to gross total resection in less than 40% of cases. If removal is complete, no further treatment is recommended. Patients with significant residual tumor postop-eratively may require further therapy if the risk of subsequent surgery to remove progressive tumor is too great.

Radiotherapy

The role of radiation is undecided. The ability to re-resect hemispheric lesions usually allows postponement of adjuvant therapy. Current trends use radiotherapy when chemotherapy has failed in unresectable symptomatic tumors. Dosing is 5000 to 5500 cGy, depending on age, to the original tumor bed with a 2-cm margin.

In deep midline locations, chemotherapy tends to be used to avoid the long-term effects of radiation to vital areas, including the pituitary.

Chemotherapy

The carboplatin-vincristine regimen is the best studied regimen in patients with newly diagnosed, progressive low-grade astrocytoma (Table 17-5). Responses occur in 56% of patients. Patients less than 5 years of age have a 3-year progression-free survival (PFS) of 74% compared with 39% in older children. A previous study demonstrated a response rate of 52% in patients with recurrent disease. The Children's Oncology Group is currently comparing the carboplatin-vincristine regimen with 6-thioguanine, procarbazine, CCNU, and vincristine. Use of single-agent

Table 17-5. Chemotherapy for Low-Grade Astrocytomas and Optic Gliomas

Induction (one 12-week cycle):

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