Treatment > Irinotecan · Temozolomide Clinical Trials

Meeting Abstract

Phase I/II study of combination temozolomide (TMZ) and irinotecan (CPT-11) for recurrent malignant gliomas: A North American Brain Tumor Consortium (NABTC) study

M. R. Gilbert, P. Wen, F. Lieberman, I. Robins, M. Mehta, W. K. A. Yung, S. Chang, L. Junck, T. Cloughesy, M. Prados

MD Anderson Cancer Ctr, Houston, TX; Dana-Farber Cancer Institute, Boston, MA; University of Pittsburgh, Pittsburgh, PA; University of Wisconsin Hospital & Clinics, Madison, WI; University of California, San Francisco, San Francisco, CA; University of Michigan, Ann Arbor, MI; University of California, Los Angeles, Los Angeles, CA.

TMZ, an oral alkylating agent, is active in recurrent malignant glioma.
CPT-11, a topoisomerase I inhibitor, has also been shown to have modest activity against recurrent malignant gliomas.
This phase I/II study is designed to determine the toxicity and efficacy of TMZ and CPT-11 in patients (pts) with recurrent malignant glioma.
Phase I was designed to determine the maximum tolerated dose (MTD) of CPT-11 in a q 2-week schedule with TMZ in pts receiving p450 enzyme inducing anticonvulsant (EIAC) (Group B), while the phase II portion was to determine the efficacy of this combination in pts not on EIAC (Group A).
TMZ was given at 150 mg/m2/d x 5, q 28d.
CPT-11 was given at 200 mg/m2, q 2-week for Group A, and 350 mg/m2 escalating to 500 mg/m2 for Group B.
Pts must have recurrent or progressive GBM, AA, AO, or AOA.
30 pts were entered into Group A (23 GBM and 7 non-GBM).
The 6 month progression free survival (PFS 6-mo) for the GBM pts is 38% (95% CI = 22%, 66%).
Of 20 pts evaluable for response, 5 achieved PR (25%), 10 NC (50%), and 5 PD (25%).
6 pts required dose reduction for neutropenia.
Only 1 pt had grade 3 diarrhea.
21 pts were entered into Group B, (350 mg-6 pts, 400 mg-4, 250 mg-3, 500 mg-8).
Response evaluation showed 1CR, 3PR, 6NC, and 7 PD.
Diarrhea appeared to be the DLT at 500 mg/m2 of CPT-11.
In summary, the combination of TMZ and CPT-11 appears tolerable.
A high response rate and an encouraging PFS 6-mo have been observed in this preliminary analysis.
The MTD of CPT-11 appeared to be 450 mg/m2 q 2-week for pts on EIAC.

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