Phase 2 trial of irinotecan and thalidomide in adults with recurrent anaplastic glioma Cancer, 04/16/2012

Giglio P et al. – The combination of thalidomide and irinotecan did not achieve sufficient efficacy to warrant further investigation against anaplastic gliomas (AGs), although a subset of patients experienced prolonged progression–free survival (PFS)/overall survival (OS). A trial of the more potent thalidomide analogue, lenalidomide, in combination with irinotecan against AG is currently ongoing.

• Adults with recurrent AG previously treated with radiation therapy, with Karnofsky performance score ≥70, adequate organ function and not on enzyme-inducing anticonvulsants were enrolled.
• Treatment was in 6-week cycles with irinotecan at 125mg/m² weekly for 4weeks followed by 2weeks off, and thalidomide at 100mg daily increased to 400mg/day as tolerated.
• The primary endpoint was progression-free survival rate at 6months (PFS-6), and the secondary endpoints were overall survival (OS) and response rate (RR).

• In 39 eligible patients, PFS-6 for the intent-to-treat population was 36% (95% confidence interval [CI]=21%, 53%), median PFS was 13weeks (95% CI=6%, 28%) and RR was 10%(95% CI=3%, 24%).
• Radiological findings included 2 complete and 2 partial responses and 17 stable disease.
• Median OS from study registration was 62weeks, (95% CI=51, 144).
• Treatment-related toxicities (grade 3 or higher) included neutropenia, diarrhea, nausea, and fatigue; 6 patients experienced venous thromboembolism.
• Four deaths were attributable to treatment-related toxicities: 1 from pulmonary embolism, 2 from colitis, and 1 from urosepsis.