Treatment > Doxorubicin · Temozolomide Clinical Trials

Meeting Abstract

Adjuvant chemotherapy with temozolomide and liposomal doxorubicine in the first-line therapy of patients with glioblastoma - a phase-II trial

P. Hau, T. Jauch, U. Baumgart, O. Grauer, B. Hirschmann, L. Kaes, H. Koch, C. Wismeth, A. Steinbrecher, U. Bogdahn

University of Regensburg, Regensburg, Germany

Background. Temozolomide (Temodar, TMZ) recently showed promising results in a pilot study on first-line therapy of glioblastoma with an overall survival of more than 16 months.
Pegylated liposomal doxorubicin (Caelyx, L-DOX) was evaluated in patients with recurrent high-grade glioma and showed an overall response rate of 40 %.
Median time to progression was 17 weeks and median overall survival after diagnosis was 74 weeks.
Therefore, a combination of both agents seems promising.

Methods. We initiated a pilot phase II-protocol with a combination regimen consisting of TMZ and L-DOX in the first-line therapy of patients with glioblastoma.
TMZ is given orally 75 mg/m2 daily during standard radiotherapy and 150-200 mg/m2 days 1-5 in 28 days starting 4 weeks after completion of radiotherapy.
L-DOX is given in a dose-escalation regimen once prior to radiotherapy and on days 1 and 15 starting 4 weeks after completion of radiotherapy.
L-DOX is escalated for 5mg/m2 in groups of three patients starting with 5 mg/m2 (group 1) and a highest dose of 20mg/m2 (group 4).
Patients are followed closely with clinical follow ups every 2 and imaging (MRI) every 4 weeks.
Primary end point is tumor progression.

Results. Up to this point, 7 patients are included in the trial.
One patient could not be evaluated.
In the first group of three patients (group 1a), one patient had pancytopenia NCI-CTC grade IV leading to exclusion from the trial.
Therefore, according to the protocol, another group of three patients was treated with the starting dose (group 1b).
All patients exept the one excluded had no significant toxicity.
Therefore, dose will be escalated after the last patient included has reached the end of the first maintainance course.
Concerning efficacy, two patients had clinical and partial responses in MRI.
One patient had tumor stabilization, all others are to early for evaluation.

Discussion. Considering first preliminary results, this regimen is feasible, tolerable, and able to induce objective responses in patients with glioblastoma using the standard dose of TMZ and 5mg/m2 of L-DOX.
Updated results will be reported at the meeting.

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