Temozolomide for recurrent intracranial supratentorial platinum-refractory ependymoma.
BACKGROUND
To the authors' knowledge, there currently is no standard therapy for platinum-resistant ependymoma; hence, a need exists for new therapies. In the current study, a retrospective evaluation of temozolomide (TMZ) in adults with recurrent, supratentorial, platinum-refractory, World Health Organization grade 2 ependymoma was performed, with an objective of determining 6-month progression-free survival (PFS).


METHODS
A total of 25 patients, ages 28 to 63 years, with recurrent ependymoma were treated. All patients had previously been treated with surgery, radiotherapy, and platinum-based chemotherapy (cisplatin in 15 patients and carboplatin in 10 patients). Nine patients underwent repeat surgery. Patients were treated at the time of second recurrence with TMZ (5 consecutive days), once every 4 weeks, which was defined as a single cycle. Neurologic evaluation was performed every 4 weeks and neuroradiographic assessment every 8 weeks.


RESULTS
A total of 68 cycles of TMZ (median, 2 cycles; range, 1-6 cycles) was administered. TMZ-related toxicity included leukopenia (7 patients; 1 with grade 3 [grade was determine according to National Cancer Institute Common Toxicity Criteria [version 3.0]), constipation (6 patients; none with grade 3), fatigue (5 patients; none with grade 3), anemia (2; none with grade 3), thrombocytopenia (2; none with grade 3), and deep vein thrombosis (2; none with grade 3). One patient (4%) demonstrated a partial radiographic response, 9 (36%) had stable disease, and 15 (60%) developed progressive disease after 2 cycles of TMZ. Time to tumor progression ranged from 1 to 7 months (median, 2 months). Survival ranged from 2 to 8 months (median, 3 months). The 6-month and 12-month PFS were 2% and 0%, respectively.


CONCLUSIONS
TMZ in this dose schedule demonstrated little efficacy in a cohort of adults with recurrent, intracranial, platinum-refractory ependymoma.
Chamberlain
Marc C
MC
Department of Neurology and Neurosurgery, University of Washington/Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA. chambemc@u.washington.edu
Johnston
Sandra K
SK
D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D016190:Carboplatin / Q000627:therapeutic use; D002945:Cisplatin / Q000627:therapeutic use; D003606:Dacarbazine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D004806:Ependymoma / Q000188:drug therapy*; D005260:Female; D005296:Ferrous Compounds; D006801:Humans; D008297:Male; D000075163:Metallocenes; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D019233:Retreatment; D015173:Supratentorial Neoplasms / Q000188:drug therapy*; D000077204:Temozolomide
D018906:Antineoplastic Agents, Alkylating; D005296:Ferrous Compounds; D000075163:Metallocenes; C009711:EX 10-478; D003606:Dacarbazine; D016190:Carboplatin; D002945:Cisplatin; D000077204:Temozolomide