A Phase I/II study everolimus in combination with paclitaxel-carboplatin in patients with advanced adenocarcinoma of the stomach

摘要: Background: Significant proportion of patients (pts) with adenocarcinoma of stomach (ADCS) present with advanced disease. Paclitaxel (P), either alone, or in combination with carboplatin (C) is well-tolerated, but has modest activity in ADCS. The PI3K-Akt pathway played an important role in cell proliferation and apoptosis in pre-clinical ADCS models. Everolimus (E) is a potent inhibitor of mTOR, a downstream mediator of the PI3K-Akt pathway. Combining chemotherapies with mTOR inhibition may improve outcomeMethods: A single-arm, dose-escalation study of E, in combination with P and C (E+ PC) was conducted in pts with metastatic and/or loco-regionally advanced ADCS [NCT01514110]. In the phase 1 portion (P1P), the maximum-tolerated dose (MTD), recommended phase 2 dose (RP2D) and safety of E+ PC, were determined using a standard 3+ 3 design. Starting dose (dose level I) was E 5mg/d, P …