Efficacy for Thalidomide, Irinotecan Combo Inadequate for Glioma
In this study, eligible patients were adults with recurrent AG previously treated with radiation therapy, Karnofsky performance score ≥70, adequate organ function, with no history of taking enzyme-inducing anticonvulsants. Patients enrolled in this study were treated in 6-week cycles with irinotecan (125mg/m2, weekly, 4 weeks on/2 weeks off) and thalidomide (100mg, daily, increased to 400mg/day, as tolerated). Primary end point: progression-free survival rate at 6 months (PFS-6); secondary end points were overall survival (OS) and response rate (RR).
The investigators reported the following results. PFS-6 for the intent-to-treat population was 36% (95% CI=3%, 24%). Radiological findings included 2 complete responses, 2 partial responses, and 17 with stable disease. Median OS from study registration was 62 weeks, (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.
The investigators concluded: “The combination of thalidomide and irinotecan did not achieve sufficient efficacy to warrant further investigation against AG, although a subset of patients experienced prolonged PFS/OS. A trial of the more potent thalidomide analogue, lenalidomide, in combination with irinotecan against AG is currently ongoing.”