Phase II trial of salvage therapy with trabectedin in metastatic pancreatic adenocarcinoma

Carmen Belli, Lorenzo Piemonti, Maurizio D'Incalci, Massimo Zucchetti, Luca Porcu, S. Cappio, Claudio Doglioni, Paola Allavena, D. Ceraulo, Paola Maggiora, Erica Dugnani, Mariagiulia Cangi, Greta Garassini, Michele Reni

Research output: Contribution to journalArticle

Abstract

Purpose: No standard salvage chemotherapy has been identified for metastatic pancreatic adenocarcinoma (mPA), and there is an urgent need for active agents against this disease. This phase II trial explored the activity of trabectedin in mPA progressing after gemcitabine-based first-line chemotherapy. Methods: Patients with gemcitabine-resistant disease received trabectedin 1.3 mg/m2 as a 3-h intravenous continuous infusion every 3 weeks until disease progression or unacceptable toxicity or for a maximum of 6 months. The primary endpoint was progression-free survival rate at 6 months (PFS-6). Since trabectedin modulates the production of selected inflammatory mediators, this study also aimed to identify inflammatory biomarkers predictive for response to trabectedin. Results: Between February 2011 and February 2012, 25 patients received trabectedin. PFS-6 was 4 %, median PFS 1.9 months (range 0.8-7.4), and median overall survival 5.2 months (range 1.1-24.3). Grade >2 toxicity consisted of neutropenia in 44 % of patients, febrile neutropenia and thrombocytopenia both in 12 %, anemia in 8 %, fatigue in 12 %, and AST and ALT increase in 8 and 4 %, respectively. Trabectedin was shown to modulate the production of inflammatory mediators, and at disease progression, levels of a subgroup of cytokines/chemokines were modified. Furthermore, tissue analysis identified 30 genes associated with better prognosis. Conclusions: Although it has shown some ability to modulate inflammatory process, single-agent trabectedin had no activity as salvage therapy for mPA.

Original languageEnglish
Pages (from-to)477-484
Number of pages8
JournalCancer Chemotherapy and Pharmacology
Volume77
Issue number3
DOIs
Publication statusPublished - Mar 1 2016

Keywords

  • Gemcitabine-resistant chemotherapy
  • Inflammatory modulation
  • Metastatic disease
  • Pancreatic cancer
  • Salvage treatment
  • Trabectedin

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Pharmacology
  • Pharmacology (medical)
  • Toxicology

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