TY - JOUR
T1 - Phase II trial of salvage therapy with trabectedin in metastatic pancreatic adenocarcinoma
AU - Belli, Carmen
AU - Piemonti, Lorenzo
AU - D'Incalci, Maurizio
AU - Zucchetti, Massimo
AU - Porcu, Luca
AU - Cappio, S.
AU - Doglioni, Claudio
AU - Allavena, Paola
AU - Ceraulo, D.
AU - Maggiora, Paola
AU - Dugnani, Erica
AU - Cangi, Mariagiulia
AU - Garassini, Greta
AU - Reni, Michele
PY - 2016/3/1
Y1 - 2016/3/1
N2 - 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.
AB - 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.
KW - Gemcitabine-resistant chemotherapy
KW - Inflammatory modulation
KW - Metastatic disease
KW - Pancreatic cancer
KW - Salvage treatment
KW - Trabectedin
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U2 - 10.1007/s00280-015-2932-3
DO - 10.1007/s00280-015-2932-3
M3 - Article
VL - 77
SP - 477
EP - 484
JO - Cancer Chemotherapy and Pharmacology
JF - Cancer Chemotherapy and Pharmacology
SN - 0344-5704
IS - 3
ER -