Treatment > Nonsteroidal Anti-Inflamm.Drugs · Temozolomide Clinical Trials

Meeting Abstract

Temozolomide plus celecoxib for treatment of malignant gliomas

S. Pannullo, J. V. Serventi, C. Balmaceda, J. Burton

New York Presbyterian Hospital-Weill Medical College of Cornell University, New York, NY; Columbia Presbyterian Hospital, New York City, NY; Staten Island University Hospital, Staten Island, NY

Background. Temozolomide (Temodar) (TMZ) is an effective agent for malignant gliomas.
Celecoxib (Celebrex) (CLBRX), a selective cyclooxygenase-2 (COX-2) inhibitor, also has potential activity in malignant gliomas.
In vitro, COX-2 is constitutively expressed in the majority of brain tumors and promotes the growth of human glioma-derived cell lines.
In vivo, CLBRX has anti-angiogenic effects, is a radiosensitizer, and may enhance chemotherapy.
This phase I/II clinical trial tests CLBRX with BID TMZ.

Methods. Eligible patients with documented histological diagnosis of relapsed or refractory glioblastoma multiforme (GBM) received TMZ 200 mg/m2 load followed by 90 mg/m2 BID x 9 over 5 days.
CLBRX was dose escalated from 60 mg/m2 BID for 10 days, to 240 mg/m2 in cohorts of 3-6 patients.
Cycles were repeated every 28 days, tumor response was assessed (MRI) every 2 cycles.

Results. Eighteen patients (13 M, 5 F) were enrolled for 66 cycles of therapy.
Prior treatment consisted of radiation (18 patients) and chemotherapy (3 patients).
Median age was 49 years (range, 39-69).
Escalation of CLBRX to 360 mg/m2 has been achieved.
Fifteen patients are evaluable for toxicity.
One patient had grade 3 leukopenia and thrombocytopenia, requiring dose reduction of TMZ.
One patient experienced grade 4 neutropenia, requiring administration of granulocyte-colony stimulating factor (G-CSF).
One patient had grade 4 hyperglycemia and one patient experienced mood alteration and depression.
6 patients (40%) had Grade I constipation and one patient had Grade 2 constipation.
In the 13 patients evaluable for response, after an average of 2 cycles, 31% of patients (4/13) had a partial response, 62% of patients (8/13) achieved stable disease (SD), and 7% (1/13) had progressive disease.
After 7 cycles, 7% (1/13) had a complete response (CR), resulting in an overall response after an average of 2 cycles of 93%.

Conclusions. TMZ BID in combination with Celecoxib is well tolerated.
Hematologic toxicity was mild and did not recur following TMZ dose reduction.
Response rates are promising.
Further accrual and follow-up is necessary to determine the maximum tolerated dose and response rates for the combination of TMZ and Celecoxib.

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