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

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.

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