title: Combination of 6-thioguanine, capecitabine, and celecoxib with temozolomide or lomustine for recurrent high-grade glioma.
abstract: We evaluated the efficacy of temozolomide (TMZ) or lomustine (CCNU) in combination with 6-thioguanine, capecitabine, and celecoxib for the treatment of recurrent high-grade glioma. Forty-three patients with recurrent glioblastoma and 31 patients with recurrent anaplastic glioma (AG) were enrolled in this open-label, non-comparative study. Patients previously treated with TMZ received CCNU while all others received TMZ; all patients received 6-thioguanine, capecitabine, and celecoxib. Endpoints were 12-month progression-free survival (PFS) for patients with AG, 6-month PFS for patients with glioblastoma, duration of PFS, and MRI-based objective response rates. Results from the TMZ and CCNU treatment arms were combined in the final analysis because there was no statistically significant difference between them. Thirty-eight patients with glioblastoma were treated with the lomustine-based regimen, and five received the TMZ-based regimen. For the 43 glioblastoma patients, the objective response rate was 12 and 33% had stable disease; the 6-month PFS was 14% and median overall survival 32 weeks. For the 31 AG patients, the combined objective response rate was 26 and 42% had stable disease; the 12 month PFS was 44%. Treatment was reasonably well tolerated with hematological toxicity common and more frequent with CCNU than TMZ. The combination therapy with 6-thioguanine, capecitabine and celecoxib plus CCNU or TMZ does not appear to be more effective than other alkylating agent schedules for patients with recurrent glioblastoma. The combination, however, is promising for patients with recurrent high-grade AG.
authors.affiliation: Department of Neuro-Oncology, Unit 0431, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, P.O. Box 301402, Houston, TX, 77230-1402, USA.
authors.forename: Tobias
authors.initials: T
authors.lastname: Walbert
authors.forename: Mark R
authors.initials: MR
authors.lastname: Gilbert
authors.forename: Morris D
authors.initials: MD
authors.lastname: Groves
authors.forename: Vinay K
authors.initials: VK
authors.lastname: Puduvalli
authors.forename: W K Alfred
authors.initials: WK
authors.lastname: Yung
authors.forename: Charles A
authors.initials: CA
authors.lastname: Conrad
authors.forename: George C
authors.initials: GC
authors.lastname: Bobustuc
authors.forename: Howard
authors.initials: H
authors.lastname: Colman
authors.forename: Sigmund H
authors.initials: SH
authors.lastname: Hsu
authors.forename: B Nebiyou
authors.initials: BN
authors.lastname: Bekele
authors.forename: Wei
authors.initials: W
authors.lastname: Qiao
authors.forename: Victor A
authors.initials: VA
authors.lastname: Levin
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy*; D000069287:Capecitabine; D000068579:Celecoxib; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D005909:Glioblastoma / Q000188:drug therapy*; D018316:Gliosarcoma / Q000188:drug therapy*; D006801:Humans; D008130:Lomustine / Q000008:administration & dosage; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000188:drug therapy*; D011446:Prospective Studies; D011720:Pyrazoles / Q000008:administration & dosage; D013449:Sulfonamides / Q000008:administration & dosage; D015996:Survival Rate; D000077204:Temozolomide; D013866:Thioguanine / Q000008:administration & dosage; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D011720:Pyrazoles; D013449:Sulfonamides; D003841:Deoxycytidine; D000069287:Capecitabine; D008130:Lomustine; D003606:Dacarbazine; D013866:Thioguanine; D000068579:Celecoxib; D005472:Fluorouracil; D000077204:Temozolomide