当前位置： SCI文献检索 > MEDICINE期刊下所有文献 > High-dose fotemustine in temozolomide-pretreated glioblastoma multiforme patients: A phase I/II trial.

High-dose fotemustine in temozolomide-pretreated glioblastoma multiforme patients: A phase I/II trial.

Abstract：

BACKGROUND:Glioblastoma multiforme (GBM) is a rare and deadly disease, with a reported average incidence rate of 3.19 cases per 100,000 inhabitants. Fotemustine, a third-generation nitrosourea with an alanine phosphor carrier that facilitates cellular penetration, has been extensively investigated in the setting of recurrent/progressive disease after initial treatment. Fotemustine is usually administered following a schedule consisting of 3 doses every week, followed by maintenance doses administered every 3 weeks. METHODS:In this phase I/II trial, we aimed to assess whether the use of a biweekly regimen allowed administration of higher dose than the standard 100 mg/m dose approved per label indication in a population of patients with recurrent GBM. In this phase I/II trial, fotemustine was administered intravenously over 1 hour every 2 weeks at either 120 or 140 mg/m doses for up to 1 year, until disease progression, unacceptable toxicity, or patient's request to withdraw from the study. The phase I part of the trial was conducted following the classic 3+3 study design. The phase II part of the trial was a single-arm study. The primary efficacy endpoint was the percentage of patients who had not progressed after 24 weeks (PFS-24). RESULTS:Thirty-seven patients were enrolled in this phase I/II trial from August 2006 to November 2011. Treatment was well tolerated in the overall population. Main severe toxicity was grades 3 and 4 thrombocytopenia, which occurred in 4 of 6 patients treated at the 140 mg/m dose level and in 3 of 31 patients treated at 120 mg/m. Median PFS and overall survival were 12.1 (1-40.2) weeks and 19.7 (1-102) weeks, respectively. CONCLUSION:We conclude that fotemustine can be safely administered at 120 mg/m biweekly. The efficacy of such modified schedule and doses should be compared to the biweekly schedule at 80 mg and the standard weekly schedule at 80 to 100 mg/m.

journal_name

Medicine (Baltimore)

journal_title

Medicine

authors

Marinelli A,Lamberti G,Cerbone L,Cordua N,Buonerba C,Peluso G,Di Lorenzo G,De Placido S

doi

10.1097/MD.0000000000011254

subject

Has Abstract

pub_date

2018-07-01 00:00:00

pages

e11254

issue

eissn

0025-7974

issn

1536-5964

pii

00005792-201807060-00017

journal_volume

pub_type

杂志文章

在线工具

High-dose fotemustine in temozolomide-pretreated glioblastoma multiforme patients: A phase I/II trial.