@article{JGO34342,
author = {Patrick Grierson and Andrea Teague and Rama Suresh and Kian-Huat Lim and Manik Amin and Katrina Pedersen and Benjamin Tan and Jesse Huffman and Nick Boice and Lingling Du and Jingxia Liu and A. Craig Lockhart and Andrea Wang-Gillam},
title = {Phase Ib/II study combining tosedostat with capecitabine in patients with advanced pancreatic adenocarcinoma},
journal = {Journal of Gastrointestinal Oncology},
volume = {11},
number = {1},
year = {2019},
keywords = {},
abstract = {Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with limited therapeutic options. We evaluated the safety and efficacy of the aminopeptidase inhibitor tosedostat with capecitabine in advanced PDAC.
Methods: We conducted a phase Ib/II trial of tosedostat with capecitabine as second-line therapy for advanced PDAC. Planned enrollment was 36 patients. Eligible patients were treated with capecitabine 1,000 mg/m2 oral twice-daily days 1–14 and oral tosedostat in a dose de-escalation design on days 1–21 of each 21-day cycle. Primary endpoints were the recommended phase 2 dose (RP2D) and progression-free survival (PFS).
Results: Sixteen patients were enrolled. Tosedostat 120 mg oral twice daily with capecitabine 1,000 mg/2 oral twice daily was the RP2D. There was one dose-limiting toxicity (DLT) (grade 3 acute coronary syndrome) during phase Ib. The most common treatment-related adverse events were gastrointestinal (nausea, diarrhea), cardiac [QTc prolongation, decreased ejection fraction (EF)], and fatigue. The median PFS was 7.1 months, and the median treatment failure free survival was 3 months. Eight patients experienced stable disease for greater than 3 months. The study was closed early due to lack of drug availability.
Conclusions: Tosedostat with capecitabine displayed tolerable toxicity, and prolonged disease control in a subset of patients. These data encourage further exploration of aminopeptidase inhibitors in pancreatic cancer.},
issn = {2219-679X}, url = {https://jgo.amegroups.org/article/view/34342}
}