TY  - JOUR
A1  - Werner, Dominique
A1  - Atmaca, Akin
A1  - Pauligk, Claudia
A1  - Pustowka, Anette
A1  - Jäger, Elke
A1  - Batran, Salah-Eddin al-
T1  - Phase I study of everolimus and mitomycin C for patients with metastatic esophagogastric adenocarcinoma
T2  - Cancer medicine
N2  - This study aimed at determining the recommended dose of the mammalian target of rapamycin inhibitor everolimus in combination with mitomycin C (MMC) in patients with previously treated metastatic esophagogastric cancer. In this phase I trial, patients received escalated doses of oral everolimus (5, 7.5, and 10 mg/day) in combination with intravenous MMC 5 mg/m2 every 3 weeks. Endpoints were the dose-limiting toxicity (DLT), safety, and response rates. Tumor tissues were tested for HER2-status and mutations in the PTEN, PIK3CA, AKT1, CTNNB1, and E-cadherin type 1 genes. Sixteen patients (12 male, four female) with gastric/gastroesophageal junction cancer were included. All patients were previously treated with a platinum-based chemotherapy. Treatment cohorts were: 5 mg/day, three patients; 7.5 mg/day, three patients; and 10 mg/day, 10 patients. No DLTs occurred during dose escalation. Most frequent grade 3 toxicities were leukopenia (18.8%) and neutropenia (18.8%). All other grade 3 toxicities were below 10%. No grade 4 toxicities occurred. Three (18.8%) patients experienced partial responses and four patients had stable disease (SD). Antitumor activity according to Response Evaluation Criteria In Solid Tumors (RECIST)-criteria was highest in the 10 mg/day cohort. No associations between HER2-status or detected mutations and response were observed. The recommended dose of everolimus combined with MMC is 10 mg/day. Encouraging signs of antitumor activity were seen (http://www.ClinicalTrials.gov; Clinical trial registration number: NCT01042782).
KW  - Esophagogastric
KW  - RAD001
KW  - everolimus
KW  - gastric
KW  - mitomycin C
Y1  - 2013
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/26751
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-267515
SN  - 2045-7634
N1  - Copyright: © 2013 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
VL  - 2
IS  - 3
SP  - 325
EP  - 333
PB  - Wiley
CY  - Hoboken, NJ
ER  -