Treatment > Temozolomide Clinical Trials · Thalidomide

Meeting Abstract

Phase II trial of daily oral temozolomide and thalidomide in newly diagnosed glioblastoma multiforme before radiation therapy

J. N. Capparella, V. M. Johnson, X. Maestri-Moden, P. Sampath, N. Ready, L. Alderson

Harvard Medical School, Boston, MA; Brown Medical School, Providence, RI

Primary brain tumors are associated with significant morbidity and mortality.
Despite multi-modality approaches to treatment, the median survival for glioblastoma multiforme (GBM) is less than 12 months.
Considering the short survival associated with GBM, attention to quality of life (QOL) is essential.
A combination oral regimen of Temozolamide and Thalidomide was selected and evaluated for efficacy and safety in pre-irradiated patients.

Methods. A Phase II single-institution study was conducted using post-surgical chemotherapy in histologically confirmed GBM.
No patient received radiation or other treatment prior to enrollment.
Patients received oral Temozolomide (75 mg/m2) administered daily for 6 weeks followed by a 4-week recovery period, in combination with daily oral Thalidomide, escalated to a maximum dose of 400 mg/day.
Patient evaluation included routine exams, labs, neuroradiographic imaging, nerve conduction studies, and QOL measurements (QLQ-C30/BN20).

Results. The study sought to enroll 20 patients.
However, it closed at the interim analysis after none of the first 7 patients responded or stabilized on treatment.
Patients' average age was 61 years, 5 male and 2 female, and all underwent aggressive surgical resection prior to enrollment.
The regimen was reasonably tolerated, with only one patient being withdrawn from the study due to toxicity.
This patient had grade 2 toxicity with anemia and fatigue, grade 4 transaminitis, and bradycardia.
Another patient died 8 days into treatment due to multi-organ system failure and sepsis with MRSA endocarditis.
All remaining patients had progression of disease.
No cases of neuropathy developed.
Median time to treatment failure was 37 days (range 8-116 days).
3 of 7 patients are still alive at a median of 11 months of follow-up, with a median survival time of 6 months (range 78-208 days).
All but one patient received post-protocol radiation, two underwent re-resections, and one received further chemotherapy.

Conclusion. Although tolerable, the combination of daily, oral Temozolomide with Thalidomide, given prior to radiation therapy, is not effective in GBM.

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