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WHO Classification:
I. TUMORS OF NEUROEPITHELIAL TISSUE
A. TUMORS OF NEUROGLIAL CELLS
1. Astrocytic Group
a. astrocytome
b. astroblastoma
c. polar spongioblastoma
2. Oligodendroglia
a. oligodendroglioma
3. Ependymoma
a. ependymoma
b. subependymoma
c. ependymoblastoma
4. Anaplastic
a. glioblastoma multiforme
B. TUMORS OF NEURONAL CELLS & PRIMITIVE BI-POTENTIAL PRECURSORS
1. Medulloepithelioma
2. Medulloblastoma & cerebellar neuroblastoma
3. Cerebellar neuroblastoma
4. Gliocytoma & ganglioglioma
C. TUMORS OF SPECIALIZED TISSUES OF CENTRAL NEUROEPITHELIAL ORIGIN
1. Neuroepithelial tumors of the retina
a. retinoblastoma
b. medulloepithelioma
c. adult astorcytoma
2. Optic nerve glioma
3. Tumors of the neurohypophysis
a. astorcytoma
b. granular cell tumor
4. Tumors of the pineal body
a. pineoblastoma
b. pineocytoma
c. astrocytoma
5. Tumors of the choroid plexus
a. papilloma
b. carcinoma
II. TUMORS OF THE NERVE SHEATH CELLS

III. TUMORS OF MENINGEAL TISSUE

IV. PRIMARY MALIGNANT LYMPHOMA

ASTROCYTOMAS
The most common malignant primary brain tumors of adults.
Gliobalstoma Multiforme- 51% of all brain tumors for patients >60 years old.

Increased Incidence of astrocytomas in certain groups of patients:
1. Neurofibromatosis
2. Osler-Weber=Rendu Syndrome
3. Tuberous Sclerosis
4. Trurcots Syndrome
5. Childhood radiation exposure
6. Li-Fraumeni Syndrome

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TEMADAR (Temazolamide)

5-DAY Regimen
Temadar 150 mg po QD X 5 days
Repeat Q28 days

Sixty-four patients were enrolled onto this open-label, phase II trial. Temozolomide (75 mg/m2/d x 7 d/wk for 6 weeks) was administered orally concomitant with fractionated radiotherapy (60 Gy total dose: 2 Gy x 5 d/wk for 6 weeks) followed by temozolomide monotherapy (200 mg/m2/d x 5 days, every 28 days for six cycles). The primary end points were safety and tolerability, and the secondary end point was overall survival.

RESULTS: Concomitant radiation plus temozolomide therapy was safe and well tolerated. Nonhematologic toxicities were rare and mild to moderate in severity. During the concomitant treatment phase, grade 3 or 4 neutropenia, thrombocytopenia, or both were observed in 6% of patients, including two severe infections with Pneumocystis carinii. During adjuvant temozolomide, 2% and 6% of cycles were associated with grade 3 and 4 neutropenia or thrombocytopenia, respectively. Median survival was 16 months, and the 1- and 2-year survival rates were 58% and 31%, respectively. Patients younger than 50 years old and patients who underwent debulking surgery had the best survival outcome.

CONCLUSION: Continuous daily temozolomide and concomitant radiation is safe. This regimen of concomitant chemoradiotherapy followed by adjuvant chemotherapy may prolong the survival of patients with glioblastoma. Further investigation is warranted, and a randomized trial is ongoing.

Combined-modality treatment with radiotherapy & temozolamide:
25 patients with recurrent high grade gliomas after standard therapy (surgery and radiation) with the following schedule: 400 mg temozolomide orally for five days repeated every 28 days, & radiotherapy at a dose of 20-30 Gy (2 x 1.2 Gy per day). Four of these patients underwent a second operation without complete tumor resection. After 125 courses of temozolomide, grade 1 (NCI-CTC) thrombocytopenia was found in four patients and grade 2 in two patients. Two patients developed grade 1 leukocytopenia & two others grade 2. CTC grade 1-2 nausea was observed in eight patients. For one patient we reduced the dose of temozolomide to 300 mg/day because of thrombocytopenia. One patient discontinued therapy after the first course because of leukocytopenia and nausea. CTC grade 3-4 side effects did not occur. Combined-modality treatment showed no more side effects than treatment with temozolomide alone. The median duration of response was 7 months. The observed side effects were tolerable. Combined treatment with radiotherapy & temozolomide is feasible. Further investigation of this agent is necessary.REF: Tumori 2002 Jan-Feb;88(1):28-31

In a randomized study: temozolomide (Temodar) vs procarbazine (Matulane) in patients with recurrent glioblastoma, PFS at 6 months = 21% & 8%, respectively. Overall survival = 60% vs 44% (P = .019) REF: Yung A, Levin VA, Albright R, et al: Proc Am Soc Clin Oncol 18:139a [abstract], 1999).

In a phase II trial (anaplastic astrocytoma), temozolomide produced a response rate (CR & PR) of 35% & a median survival of 13.6 months
REF: Yung AWR, Prados MD, Yaya-Tur R, et al: J Clin Oncol 17:27622771, 1999).

Side Effects: Thrombocytopenia, lymphopenia, nausea

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PCV

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TAMOXIFEN

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CARBOPLATIN

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IRINOTECAN

IRINOTECAN 125 mg/m2 as 90-minute intravenous (IV) infusion Q week X 4 weeks followed by a 2-week rest.

REF= JCO 17(5):1516, 1999
N=60 (all were assessable); 9 (15%; 95% confidence interval, 6% to 24%) had a confirmed PR, 33 (55%) achieved stable disease lasting more than two courses (12 weeks). Toxicity observed during the study was limited to infrequent neutropenia, nausea, vomiting, and diarrhea.
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CancerNetwork PDQ Web Site

TREATMENT RECOMMENDATIONS
Low grade astrocytomas
1. Complete gross resection
2. XRT for incomplete resections
3. Chemotherapy has no role in adult low--grade gliomas. Some data suggests carboplatin may stabilize tumors in children.
Hig-grade astrocytomas
1. Extensive surgery
2. Post-op chemotherapy folowed by XRT (superior to XRT alone)
3. Post-op XRT alone