title: Salvage chemotherapy with procarbazine and fotemustine combination in the treatment of temozolomide treated recurrent glioblastoma patients.
abstract: The purpose of this study was to evaluate safety and efficacy of Procarbazine (PCB) and fotemustine (FTM) combination in the treatment of pre-temozolomide treated, recurrent GBM patients. The primary end-point was progression free survival at 6 months (PFS-6). Secondary end-points were overall survival, response rates (CR + PR) and toxicity. About 54 patients (41 men and 13 women) aged 26-68 years (median age, 53.5 years) with recurrent GBM were treated. PCB was administered as an oral dosage of 450 mg on days 1-2 and a total dose of 300 mg on day 3. FTM was administered on day 3, 3 h after the last PCB intake at a dose of 110 mg/mq/BSA. The treatment was repeated every 5 weeks. Treatment was continued for a maximum of six cycles or until disease progression. After two cycles of chemotherapy: 6 patients (11.2%) experienced a neuroradiographic partial response (PR), 29 patients (53.7%) had stable disease (SD), and 19 patients (35.1%) had progressive disease (PD). For the whole group of patients, the median PFS was 19.3 weeks (95% CI, 14.1-24.4 weeks), and PFS-6 was 26.7% (95% CI, 10.6-42.8%). Overall MST from the beginning of PCB + FTM chemotherapy was 28.7 weeks (95% CI, 24.8-32.7 weeks). At 6 and 12 months, 64.4% (95% CI, 51.5-77.3%) and 23.6% (95% CI, 10.1-37.1%) of patients were alive. The median survival time calculated from the first diagnosis was 20.8 months (95% CI, 16.7-24.8). We concluded that the PCB + FTM combination as done in the current trial for patients with recurrent GBM after treatment with TMZ showed some benefit with regards to increased survival and that a Phase III trial is warranted.
authors.affiliation: Department of Neuro-Oncology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy. silvani@istituto-besta.it
authors.forename: Antonio
authors.initials: A
authors.lastname: Silvani
authors.forename: Elena
authors.initials: E
authors.lastname: Lamperti
authors.forename: Paola
authors.initials: P
authors.lastname: Gaviani
authors.forename: Marica
authors.initials: M
authors.lastname: Eoli
authors.forename: Anna
authors.initials: A
authors.lastname: Fiumani
authors.forename: Andrea
authors.initials: A
authors.lastname: Salmaggi
authors.forename: Chiara
authors.initials: C
authors.lastname: Falcone
authors.forename: Graziella
authors.initials: G
authors.lastname: Filippini
authors.forename: Andrea
authors.initials: A
authors.lastname: Botturi
authors.forename: Amerigo
authors.initials: A
authors.lastname: Boiardi
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality; D009607:Nitrosourea Compounds / Q000008:administration & dosage / Q000009:adverse effects; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000009:adverse effects; D011344:Procarbazine / Q000008:administration & dosage / Q000009:adverse effects; D016879:Salvage Therapy / Q000379:methods*; D000077204:Temozolomide
chemical_list: D009607:Nitrosourea Compounds; D009943:Organophosphorus Compounds; D011344:Procarbazine; D003606:Dacarbazine; C054368:fotemustine; D000077204:Temozolomide