The temozolomide RESCUE study: A phase II trial of continuous (28/28) dose-intense temozolomide (TMZ) after progression on conventional 5/28 day TMZ in patients with recurrent malignant glioma

Antiangiogenic Strategies for Treatment of Malignant Gliomas

“…[97][98][99] Recently, two reports evaluating low-dosed, frequently administered temozolomide schedules in recurrent GBM patients documented modest gains in PFS6 proportions, relative to historical controls. 100,101 Clinical trials evaluating the addition of bevacizumab to metronomic chemotherapy are ongoing, as this strategy has greater antiangiogenic efficacy in preclinical models. 102 It should be noted, however, that antitumor activity of prolonged temozolomide dosing could also be attributed to the higher cumulative doses and the MGMT enzyme depletion that these schedules achieve.…”

Economics of Malignant Gliomas: A Critical Review

“…For newly diagnosed GBM, new extended-dose trials for TMZ showed a benefit over procarbazine, but insufficient to receive approval in the United States. [23][24][25] Preliminary data highlight potential survival benefits in a subset of glioblastoma patients with methylated methylguaninemethyltransferase (MGMT) gene promoters 26 ; the MGMT repair enzyme has the ability to revert the DNA damage induced by alkylating agents like TMZ, thus silencing of the gene increases the effectiveness of TMZ therapy.…”

Neuro-oncology: a selected review of ASCO 2011 abstracts

“…In the only randomized trial, afatinib, an irreversible tyrosine kinase EGFR inhibitor, was compared with ddTMZ and to the combination of ddTMZ and afatinib in 120 patients with first recurrent GBM [45]. Afatinib was found not to be active, whereas ddTMZ with or without afatinib demonstrated a PFS-6 of approximately 20%, a result not dissimilar to the Canadian TMZ re-challenge RESCUE trial [57]. In an ana lysis of patients with overexpressed variant 3 EGFR, a suggestion of afatinib response was observed.…”

“…A study of 31 patients with the novel mitotic spindle and vascular disrupting agent verubilin was found to be inactive (mPFS: 1.8 months). Last, an interesting trial of the novel nitrosourea fotemustine in 119 patients suggested similar activity to that of the Canadian TMZ RESCUE trial wherein three groups of patients were analyzed with respect to failure on sdTMZ (progression on sdTMZ and within 6 months of completion of CRT; progression on sdTMZ while on post-RT sdTMZ for >6 months and progression after completion of post-RT sdTMZ) [51,57]. These data confirm the nitrosourea to be a valid salvage therapy for GBM progression following sdTMZ similar to that reported in the enzastaurin and cediranib trials [28,59].…”