title: Carboplatin and oral cyclophosphamide combination after temozolomide failure in malignant gliomas.
abstract: BACKGROUND
  Temozolomide is a novel cytotoxic agent for malignant gliomas. However, treatment failure occurs approximately in half of patients, and the optimal regimen in this setting has yet to be defined. In the present study, we assessed retrospectively the efficacy and toxicity of the combination of carboplatin and oral cyclophosphamide in temozolomide-resistant patients.
  
  
  METHODS
  We evaluated the medical records of 30 patients with malignant gliomas. After failure of temozolomide therapy, patients were treated with a combination of carboplatin and oral cyclophosphamide. Treatment consisted of intravenous carboplatin AUC 6 (based on the Calvert Formula) on day 1 and oral cyclophosphamide 75 mg/m2 daily on days 1 to 14, followed by 14 days of rest, with the treatment repeated every 4 weeks.
  
  
  RESULTS
  All patients were evaluated for response and toxicity. The objective response rate was 30%, including 9 partial responses. Median time to disease progression and median overall survival was 7 months and 8 months, respectively. Clinically responsive patients had statistically significant longer progression-free survival and overall survival than unresponsive patients. Hematological side effects were commonly observed toxicities, with neutropenia the most frequent.
  
  
  CONCLUSIONS
  Our data suggest that carboplatin and oral cyclophosphamide therapy is a convenient regimen after failure of temozolomide therapy in patients with malignant gliomas because of its activity, feasibility and tolerability. Further prospective studies are needed in this setting.
authors.affiliation: Department of Medical Oncology, Gazi University, Faculty of Medicine, Ankara, Turkey.
authors.forename: Emel
authors.initials: E
authors.lastname: Yaman
authors.forename: Suleyman
authors.initials: S
authors.lastname: Buyukberber
authors.forename: Aytug
authors.initials: A
authors.lastname: Uner
authors.forename: Ugur
authors.initials: U
authors.lastname: Coskun
authors.forename: Deniz
authors.initials: D
authors.lastname: Yamac
authors.forename: Banu
authors.initials: B
authors.lastname: Ozturk
authors.forename: Ali Osman
authors.initials: AO
authors.lastname: Kaya
authors.forename: Ramazan
authors.initials: R
authors.lastname: Yildiz
authors.forename: Mustafa
authors.initials: M
authors.lastname: Benekli
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy*; D016190:Carboplatin / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008499:Medical Records; D008875:Middle Aged; D012189:Retrospective Studies; D000077204:Temozolomide; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D003520:Cyclophosphamide; D016190:Carboplatin; D000077204:Temozolomide