A phase I trial of the farnesyl transferase inhibitor, SCH 66336, with temozolomide for patients with malignant glioma

作者：Desjardins Annick^*; Reardon David A; Peters Katherine B; Threatt Stevie; Coan April D; Herndon James E II; Friedman Allan H; Friedman Henry S; Vredenburgh James J

来源：Journal of Neuro-Oncology, 2011, 105(3): 601-606.

DOI：10.1007/s11060-011-0627-0

• SCH 33663
• Lonafarnib
• Malignant glioma
• Glioblastoma

We conducted a phase I clinical trial of the combination of SCH 66336 with temozolomide administered on the standard 5-day dosing schedule. The primary objective was to determine the maximum tolerated dose and dose limiting toxicity (DLT) of twice daily SCH 66336 when administered with temozolomide to adults with malignant glioma previously treated with radiation therapy. Patients were enrolled to two strata: stratum A, patients not on enzyme-inducing antiepileptic drugs (EIAEDs); stratum B, patients receiving EIAEDs. Temozolomide was administered at a dose of 150 mg/m(2) daily for five days for the first 28-day cycle and escalated to 200 mg/m(2), during subsequent cycles. SCH 66336 was administered twice daily on a continuous daily dosing schedule. The starting dose of SCH 66336 was 75 mg twice daily for stratum A and 125 mg twice daily for stratum B. Cohorts of 3-6 patients were treated per dose level until DLT was observed. Thirty six patients were enrolled on study, including 21 patients on stratum A and 15 on stratum B. All DLTs were grade 3 events and included hepatic, gastrointestinal, renal, thrombotic and constitutional events. No grade 4 or 5 toxicities were observed. The phase II dose of SCH 66336 when combined with temozolomide is 150 mg twice daily for patients not on EIAEDs and 175 mg twice daily for patients on EIAEDs.

• 出版日期2011-12