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

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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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Acknowledgments

This work was supported by unrestricted grant from PharmaMar which also supplied trabectedin. PharmaMar did not have any role in study design, collection, analysis, interpretation of data, or writing the report. We thank Ray Hill, an independent medical writer, who provided medical writing support and journal styling prior to submission on behalf of Health Publishing and Services Srl.

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Authors and Affiliations

  1. Department of Medical Oncology, San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy

    Carmen Belli, Domenica Ceraulo, Paola Maggiora & Michele Reni

  2. Diabetes Research Institute, San Raffaele Scientific Institute, 20132, Milan, Italy

    Lorenzo Piemonti & Erica Dugnani

  3. Department of Oncology, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, 20156, Milan, Italy

    Maurizio D’Incalci, Massimo Zucchetti & Luca Porcu

  4. Department of Radiology, San Raffaele Scientific Institute, 20132, Milan, Italy

    Stefano Cappio

  5. Pathology Unit, San Raffaele Scientific Institute, 20132, Milan, Italy

    Claudio Doglioni, Maria Giulia Cangi & Greta Garassini

  6. Department Immunology and Inflammation, IRCCS Clinical and Research Institute Humanitas, 20089, Rozzano, Milan, Italy

    Paola Allavena

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  1. Carmen Belli
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Correspondence to Michele Reni.

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Belli, C., Piemonti, L., D’Incalci, M. et al. Phase II trial of salvage therapy with trabectedin in metastatic pancreatic adenocarcinoma. Cancer Chemother Pharmacol 77, 477–484 (2016). https://doi.org/10.1007/s00280-015-2932-3

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  • DOI: https://doi.org/10.1007/s00280-015-2932-3

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