Temozolomide Concomitant and Sequential to Radiotherapy as First Line of Treatment in Glioblastoma Multiforme: An Ongoing Multicentric Phase 2 Trial

Reviewer: Heather Jones, MD
Last Modified: October 9, 2002

Presenter: L. Fatigante
Presenter's Affiliation: Department of Oncology, Radiotherapy, Pisa, IT
Type of Session: Scientific


    Glioblastoma Multiforme (GBM) is associated with a high rate of local recurrence after primary therapy and a high mortality rate. In spite of aggressive treatment with surgery, radiotherapy and chemotherapy, median reported survival is less then 1 year. Temozolomide (TMZ), an oral alkylating agent, seems to have activity in GBM, particularly when combined with radiotherapy (RT). This study is a multicentric phase II study to evaluate efficacy and toxicity of TMZ concomitant and sequential to RT.

Materials and Methods

  • 88 patients (pts) with histologically proven GBM were accrued
  • The median age was 60.9 years (36-84); median PS (ECOG) 1(0-2).
  • Surgical approaches included: 14 biopsies, 29 total resections, 45 subtotal.
  • RT was delivered with Linac 4-6 MV using multiple shielded fields or multileaf collimator; total dose 60 Gy (2Gy/fx)
  • All pts received TMZ concomitant to RT (75 mg/m2/day 1h before RT 7 days/week).
  • Pts tumor progression free (by CT or MRI scan), started sequential TMZ, 28 days after the end of RT.
  • The dose was 150 mg/m2/day (1st cycle), 200 mg/m2/day (2nd-6th cycle), 5 days every 4 weeks.
  • At the time of analysis 30 pts completed the treatment schedule and 58 are in progress. 9 pts are in the concomitant phase, 49 in the sequential phase.


  • Median follow-up at time of analysis was 13.1 months (range 4-22.3).
  • After RT+TMZ a total of 79 pts were available for analysis: 25 pts are NED (after radical surgery), 12 pts scored as Partial Remission (PR), 18 pts had Stable Disease (SD), 21 pts had Progression of Disease (PD)
  • In 30 pts who completed the protocol 11 are NED, 2 PR, 7 SD, 6 PD, 4 not evaluable. Overall survival (Kaplan-Meier) was: 84 % at 12 months, 32% at 22 months. The median survival for the group was 10.4 (3.3-22.3).
  • The most common treatment related adverse events in concomitant phase were: 1 fever, 2 rash, 3 thrombocytopenia (one grade), 1 grade 2 neutropenia, 6 grade 2 vomiting.

Author's Conclusions

    The use of TMZ and RT in concomitant and sequential combination appears to be effective, safe and well tolerated. The preliminary results of response rate and survival suggest further studies are warranted. The authors plan to increase the TMZ cycles in responders or to attempt a new schedule of drug delivery based of pharmacokinetic data.

Clinical/Scientific Implications

    Temozolomide is an oral chemotherapy that may be better tolerated than the more commonly used procarbazine and has a predictable and short nadir period. These features make it a popular choice for a drug in new combination regimens. Given our less than favorable treatment record in GBM we look forward to future studies with this promising agent. Becuase this study is still in progress, it is too early to make any strong conclusions based on this trial.

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