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:
2. Osler-Weber=Rendu Syndrome
3. Tuberous Sclerosis
4. Trurcots Syndrome
5. Childhood radiation exposure
6. Li-Fraumeni Syndrome
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
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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