title: Paclitaxel poliglumex, temozolomide, and radiation for newly diagnosed high-grade glioma: a Brown University Oncology Group Study.
abstract: OBJECTIVE
  Paclitaxel poliglumex (PPX), a drug conjugate that links paclitaxel to poly-L-glutamic acid, is a potent radiation sensitizer. Prior studies in esophageal cancer have demonstrated that PPX (50 mg/m/wk) can be administered with concurrent radiation with acceptable toxicity. The primary objective of this study was to determine the safety of the combination of PPX with temozolomide and concurrent radiation for high-grade gliomas.
  
  
  METHODS
  Eligible patients were required to have WHO grade 3 or 4 gliomas. Patients received weekly PPX (50 mg/m/wk) combined with standard daily temozolomide (75 mg/m) for 6 weeks with concomitant radiation (2.0 Gy, 5 d/wk for a total dose of 60 Gy).
  
  
  RESULTS
  Twenty-five patients were enrolled, 17 with glioblastoma and 8 with grade 3 gliomas. Seven of 25 patients had grade 4 myelosuppression. Hematologic toxicity lasted up to 5 months suggesting a drug interaction between PPX and temozolomide. For patients with glioblastoma, the median progression-free survival was 11.5 months and the median overall survival was 18 months.
  
  
  CONCLUSIONS
  PPX could not be safely combined with temozolomide due to grade 4 hematologic toxicity. However, the favorable progression-free and overall survival suggest that PPX may enhance radiation for glioblastoma. A randomized study of single agent PPX/radiation versus temozolomide/radiation for glioblastoma without MGMT methylation is underway.
authors: *The Brown University Oncology Group, Providence, RI †Maine Medical Center, Portland, ME.
authors: Suriya
authors: S
authors: Jeyapalan
authors: Jerrold
authors: J
authors: Boxerman
authors: John
authors: J
authors: Donahue
authors: Marc
authors: M
authors: Goldman
authors: Timothy
authors: T
authors: Kinsella
authors: Thomas
authors: T
authors: Dipetrillo
authors: Devon
authors: D
authors: Evans
authors: Heinrich
authors: H
authors: Elinzano
authors: Maria
authors: M
authors: Constantinou
authors: Edward
authors: E
authors: Stopa
authors: Yakub
authors: Y
authors: Puthawala
authors: Deus
authors: D
authors: Cielo
authors: Alyson
authors: A
authors: Santaniello
authors: Adetokunbo
authors: A
authors: Oyelese
authors: Kalyan
authors: K
authors: Mantripragada
authors: Kayla
authors: K
authors: Rosati
authors: Debora
authors: D
authors: Isdale
authors: Howard
authors: H
authors: Safran
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001918:Brachytherapy; D001932:Brain Neoplasms / Q000401:mortality / Q000628:therapy*; D059248:Chemoradiotherapy / Q000379:methods*; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D005910:Glioma / Q000401:mortality / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000031:analogs & derivatives; D011099:Polyglutamic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D016019:Survival Analysis; D000077204:Temozolomide
chemical_list: D011099:Polyglutamic Acid; D003606:Dacarbazine; D017239:Paclitaxel; C509139:paclitaxel poliglumex; D000077204:Temozolomide