title: Protracted low doses of temozolomide for the treatment of patients with recurrent glioblastoma: A phase II study.
abstract: O(6)-alkylguanine-DNA alkyltransferase (AGAT), involved in temozolomide-induced DNA damage repair, plays a key role in the efficacy of temozolomide. AGAT activity may be reduced by protracted temozolomide doses. On the basis of the preclinical findings, we treated patients with a histologically-proven diagnosis of glioblastoma (GBM) following adjuvant temozolomide failure with a low protracted dose of temozolomide (130 mg/m(2)/day, days 1-7 and 15-21, every 4 weeks). The primary endpoint of the study was 6-month progression-free survival (PFS-6 m). The secondary endpoints were overall survival (OS) from the start of temozolomide alternative schedule and toxicity. Enrolment was ceased at 27 patients due to the lack of effectiveness of this regimen. Results indicate that our schedule is well-tolerated, but ineffective in patients with GBM and further strategies are required to improve the outcome of these patients.
authors.affiliation: Department of Medical Oncology.
authors.forename: Matteo
authors.initials: M
authors.lastname: Santoni
authors.forename: Alessandro
authors.initials: A
authors.lastname: Paccapelo
authors.forename: Luciano
authors.initials: L
authors.lastname: Burattini
authors.forename: Maristella
authors.initials: M
authors.lastname: Bianconi
authors.forename: Massimo
authors.initials: M
authors.lastname: Cardinali
authors.forename: Letizia
authors.initials: L
authors.lastname: Fabbietti
authors.forename: Roberto
authors.initials: R
authors.lastname: Trignani
authors.forename: Franco
authors.initials: F
authors.lastname: Rychlicki
authors.forename: Stefano
authors.initials: S
authors.lastname: Cascinu