Temozolomide in Patients with Glioblastoma at Second Relapse after First Line Nitrosourea-Procarbazine Failure: A Phase II Study

Abstract

Objectives: To investigate the efficacy of temozolomide (TMZ) in relationship to progression free survival at 6 months (PFS-6), median time to progression (TTP), response rate and toxicity, a phase II study was conducted in patients with recurrent glioblastoma multiforme (GBM) following surgery plus radiotherapy and a first-line regimen based on nitrosourea, procarbazine and vincristine. Methods: Forty-two patients with GBM were administered TMZ at the dose of 150 mg/m²/daily for 5 days every 4 weeks. Results: The PFS-6 and at 12 months (PFS-12) was 24% (95% Confidence Interval [CI] = 14–42%) and 8% (CI = 2–27%), respectively, with a median TTP of 11.7 weeks (CI = 9–22 weeks). The response was assessed in all 42 patients; we observed 2 complete responses (CR) (4.7%), 6 partial responses (PR) (14.3%), and 9 stable disease (SD) (21.4%), with CR+PR = 19% (CI = 7–31%). Conclusion: TMZ as a second line regimen is a valid option in patients with heavily pretreated GBM.

Therapeutic options in recurrent glioblastoma—An update

“…Both trials used a schedule of TMZ 150-200 mg/m 2 for 5 out of 28 days. Other prospective studies mainly without previous TMZ treatment using this schedule showed similar PFS-6 rates ranging from 21 to 24% [64][65][66][67].…”

Temozolomide 3 weeks on and 1 week off as first-line therapy for recurrent glioblastoma: phase II study from gruppo italiano cooperativo di neuro-oncologia (GICNO)

“…In the three available studies investigating this regimen in this setting, PFS-6 was 21% (Yung et al, 2000) (CI:13 -29%), 18% (Brada et al, 2001) (CI:11 -24%), and 24% (Brandes et al, 2002) (CI:14 -42%). As the antitumour activity of TMZ depends on the level of AGAT within tumour cells, several trials have aimed to deplete AGAT via a continuous dosing schedule (Tolcher et al, 2003).…”

Nonsurgical Treatment of Recurrent Glioblastoma

“…Some studies have evaluated extended-dose tmz schemes so as to increase depletion of O 6 -alkylguanine dna alkyltransferase (mgmt). Other studies have compared the tmz monotherapy schedules with the standard tmz schedule (150-200 mg/ m 2 for 5 days every 4 weeks) [22][23][24] . Results with extended metronomic tmz schedules of 75-100 mg/m 2 daily have also been reported [25][26][27][28][29] .…”