Phase Ib/II study combining tosedostat with capecitabine in patients with advanced pancreatic adenocarcinoma Article

Full Text via DOI: 10.21037/jgo.2019.11.06 PMID: 32175106 Web of Science: 000514838100007

Cited authors

  • Grierson, Patrick; Teague, Andrea; Suresh, Rama; Lim, Kian-Huat; Amin, Manik; Pedersen, Katrina; Tan, Benjamin; Huffman, Jesse; Boice, Nick; Du, Lingling; Liu, Jingxia; Lockhart, A. Craig; Wang-Gillam, Andrea


  • 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/m(2) 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. ibsedostat 120 mg oral twice daily with capecitabine 1,000 mg/m(2) oral twice daily was the RP2D. There was one dose-limiting toxicity (DUD (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 dosed 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.

Publication date

  • 2020

Published in


International Standard Serial Number (ISSN)

  • 2078-6891

Start page

  • 61

End page

  • 67


  • 11


  • 1