Carboxyamidotriazole orotate (CTO) plus temozolomide (TMZ) or chemoradiation may be safe and effective among patients with glioblastoma (GBM) or anaplastic glioma (AG), according to a study published in the Journal of Clinical Oncology.1

For this phase 1B study ( Identifier: NCT01107522), researchers enrolled 47 patients and assigned them to 1 of 2 cohorts. In cohort 1, patients with recurrent GBM/AG were treated with escalating CTO (219 to 812.5 mg/m2once daily or 600 mg fixed once-daily) plus TMZ; in cohort 2, patients newly diagnosed with GBM received escalating doses of CTO (219 to 481 mg/m2once daily) plus radiotherapy and TMZ.

CTO did not disrupt TMZ levels. Although toxicities were observed including fatigue, constipation, nausea, and hypophosphatemia, none were dose-limiting; the recommended phase 2 dose was 600 mg once daily.

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In cohort 1, 1 and 6 patients had complete and partial responses, respectively.

In cohort 2, patients had a median progression-free survival of 15 months, and the median overall survival (OS) was not reached after a median follow-up of 28 months. The 2-year OS rate was 62%. EGFR-amplified tumors, furthermore, had a high rate of response (P= .005).

The authors concluded that “[o]n the basis of the favorable toxicity profile, brain penetration, and encouraging activity observed in this difficult-to-treat population of patients with GBM and AG, randomized phase II trials with CTO in combination with TMZ or chemoradiation are planned.”


  1. Omuro A, Beal K, McNeill K, et al. Multicenter phase IB trial of carboxyamidotriazole orotate and temozolomide for recurrent and newly diagnosed glioblastoma and other anaplastic gliomasJ Clin Oncol. 2018 Apr 23. doi: 10.1200/JCO.2017.76.9992 [Epub ahead of print]