CPT-11 for recurrent temozolomide-refractory 1p19q co-deleted anaplastic oligodendroglioma.
OBJECTIVE
A Phase II study of CPT-11 in adults with recurrent, temozolomide (TMZ)-refractory, 1p19q co-deleted, anaplastic oligodendroglioma (AO) with a primary objective of determining 6-month progression free survival (PFS).


BACKGROUND
There is no standard therapy for alkylator-resistant AO.


METHODS
Twenty-two patients (11 men; 11 women) ages 26-65 (median 40), with radiographically recurrent AO were enrolled. All patients had previously been treated with surgery, involved-field radiotherapy, and adjuvant chemotherapy (TMZ in 15; BCNU in 6). Fifteen patients were treated at first recurrence with an alternative chemotherapy. 13 patients underwent repeat surgery. All patients were treated at either first or second recurrence with CPT-11 administered intravenously once every 3 weeks. Neurological and neuroradiographic evaluations were performed every 8-9 weeks.


RESULTS
All patients were evaluable for toxicity and response. A total of 141 cycles of CPT-11 (median 3 cycles; range 3-18) were administered. CPT-11 related toxicity included diarrhea (14 patients; 4 grade 3), neutropenia (8; 4 grade 3), fatigue (12; 3 grade 3), and delayed nausea/vomiting (12; 3 grade 3). 5 patients (23%) demonstrated a partial radiographic response, 8 (36%) demonstrated stable disease and 9 (41%) had progressive disease following three cycles of CPT-11. Time to tumor progression ranged from 2 to 13.5 months (median: 4.5 months). Survival ranged from 3 to 21 months (median: 5.5 months). Six-month and 12-month PFS were 33% and 4.5% respectively.


CONCLUSIONS
CPT-11 demonstrated modest efficacy (similar to other salvage glioma regimens) with acceptable toxicity in this cohort of adults with recurrent, 1p19q co-deleted AO all of whom had failed prior TMZ chemotherapy.
Chamberlain
Marc C
MC
Department of Neurology and Neurological Surgery, University of Washington, Seattle, WA, USA. chambemc@u.washington.edu
Glantz
Michael J
MJ
D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D003606:Dacarbazine / Q000009:adverse effects / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D009837:Oligodendroglioma / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D016019:Survival Analysis; D000077204:Temozolomide
D018906:Antineoplastic Agents, Alkylating; D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D003606:Dacarbazine; D002166:Camptothecin; D000077204:Temozolomide