title: Imatinib in combination with hydroxyurea versus hydroxyurea alone as oral therapy in patients with progressive pretreated glioblastoma resistant to standard dose temozolomide.
abstract: A randomized, multicenter, open-label, phase 3 study of patients with progressive, recurrent glioblastoma multiforme (GBM) for whom front-line therapy had failed was conducted. This study was designed to determine whether combination therapy with imatinib and hydroxyurea (HU) has superior antitumor activity compared with HU monotherapy in the treatment of recurrent GBM. The target population consisted of patients with confirmed recurrent GBM and an Eastern Cooperative Oncology Group performance status of 0-2 who had completed previous treatment comprising surgical resection, irradiation therapy, and first-line chemotherapy (preferably temozolomide (TMZ) containing regimen) and who have progressed despite treatment. If first-line chemotherapy did not contain TMZ, a second completed chemotherapy was acceptable. The primary efficacy parameter was progression-free survival (PFS). The primary comparison of combination therapy versus monotherapy for PFS was not significant (adjusted P = 0.56). The hazard ratio (HR) (adjusted HR = 0.93) was not clinically relevant. The median PFS for the combination arm was low at 6 weeks and similar to the median PFS in the monotherapy arm (6 weeks). The 6-month PFS for the two treatment groups was very similar (5% in the combination arm vs. 7% in the monotherapy arm). No clinically meaningful differences were found between the two treatment arms, and the primary study end point was not met. Among the patients receiving imatinib, no adverse events were reported that were either previously unknown or unexpected as a consequence of the disease.
authors.affiliation: Zentrum für Neuro-Onkologie am Arztehaus Velen, Ignatiusstrasse 8, 46342, Velen, Germany. gdresemann@aol.com
authors.forename: Gregor
authors.initials: G
authors.lastname: Dresemann
authors.forename: Michael
authors.initials: M
authors.lastname: Weller
authors.forename: Mark A
authors.initials: MA
authors.lastname: Rosenthal
authors.forename: Ulrich
authors.initials: U
authors.lastname: Wedding
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wagner
authors.forename: Erik
authors.initials: E
authors.lastname: Engel
authors.forename: Bernhard
authors.initials: B
authors.lastname: Heinrich
authors.forename: Regine
authors.initials: R
authors.lastname: Mayer-Steinacker
authors.forename: Anders
authors.initials: A
authors.lastname: Karup-Hansen
authors.forename: Oystein
authors.initials: O
authors.lastname: Fluge
authors.forename: Anna
authors.initials: A
authors.lastname: Nowak
authors.forename: Maximilian
authors.initials: M
authors.lastname: Mehdorn
authors.forename: Eberhard
authors.initials: E
authors.lastname: Schleyer
authors.forename: Dietmar
authors.initials: D
authors.lastname: Krex
authors.forename: Ian N
authors.initials: IN
authors.lastname: Olver
authors.forename: Joachim P
authors.initials: JP
authors.lastname: Steinbach
authors.forename: Christian
authors.initials: C
authors.lastname: Hosius
authors.forename: Christian
authors.initials: C
authors.lastname: Sieder
authors.forename: Greg
authors.initials: G
authors.lastname: Sorenson
authors.forename: Richard
authors.initials: R
authors.lastname: Parker
authors.forename: Zariana
authors.initials: Z
authors.lastname: Nikolova
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects; D001549:Benzamides; D001932:Brain Neoplasms / Q000188:drug therapy*; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000009:adverse effects / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use*; D000068877:Imatinib Mesylate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D010879:Piperazines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D000077204:Temozolomide; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D003606:Dacarbazine; D000068877:Imatinib Mesylate; D006918:Hydroxyurea; D000077204:Temozolomide
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