Phase 1 dose escalation trial of TAS-102 (trifluridine/tipiracil) and temozolomide in the treatment of advanced neuroendocrine tumors

This study evaluated the safety of TAS-102 in combination with TMZ in patients in neuroendocrine tumors. Escalating doses of TMZ (100, 150 and 200  mg/m2) on days 8 –12 were given in combination with TAS-102 (35 mg/m2 twice a day) on days 1 –5 and 8–12 of a 28 day cycle in subjects with advanced NETs. Primary endpoints were safety and determination of maximum tolerated dose (MTD). Growth factor support was mandated starting with level 2 to avoid treatment delays. Fifteen evaluable subjects were enrolled in the phase 1 study. No d ose limiting toxicities (DLTs) were observed on level 1. One DLT was observed on level 2 (grade 3 fatigue and inability to resume treatment), and 1 on level 3 (grade 4 thrombocytopenia). The most common grade ≥ 3 adverse events included neutropenia (33%), lymphopenia (27%), and thrombocytopeni a (27%). Disease control rate of 92% and partial response rate of 8% were observed in 13 evaluable subjects. This study established MTD of TAS-102 (35 mg/m2 twice daily) and TMZ (200  mg/m2 daily). This regimen was well tolerated. Early signs of clinically meaningful activity were observed. Further evaluation of the efficacy of this regimen is warranted.
Source: Investigational New Drugs - Category: Drugs & Pharmacology Source Type: research