title: Phase II trial of salvage therapy with trabectedin in metastatic pancreatic adenocarcinoma.
abstract: OBJECTIVE
  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/m(2) 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.
authors.affiliation: Department of Medical Oncology, San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy.
authors.forename: Carmen
authors.initials: C
authors.lastname: Belli
authors.affiliation: Diabetes Research Institute, San Raffaele Scientific Institute, 20132, Milan, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Piemonti
authors.affiliation: Department of Oncology, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, 20156, Milan, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: D'Incalci
authors.affiliation: Department of Oncology, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, 20156, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Zucchetti
authors.affiliation: Department of Oncology, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, 20156, Milan, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Porcu
authors.affiliation: Department of Radiology, San Raffaele Scientific Institute, 20132, Milan, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Cappio
authors.affiliation: Pathology Unit, San Raffaele Scientific Institute, 20132, Milan, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Doglioni
authors.affiliation: Department Immunology and Inflammation, IRCCS Clinical and Research Institute Humanitas, 20089, Rozzano, Milan, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Allavena
authors.affiliation: Department of Medical Oncology, San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy.
authors.forename: Domenica
authors.initials: D
authors.lastname: Ceraulo
authors.affiliation: Department of Medical Oncology, San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Maggiora
authors.affiliation: Diabetes Research Institute, San Raffaele Scientific Institute, 20132, Milan, Italy.
authors.forename: Erica
authors.initials: E
authors.lastname: Dugnani
authors.affiliation: Pathology Unit, San Raffaele Scientific Institute, 20132, Milan, Italy.
authors.forename: Maria Giulia
authors.initials: MG
authors.lastname: Cangi
authors.affiliation: Pathology Unit, San Raffaele Scientific Institute, 20132, Milan, Italy.
authors.forename: Greta
authors.initials: G
authors.lastname: Garassini
authors.affiliation: Department of Medical Oncology, San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy. reni.michele@hsr.it.
authors.forename: Michele
authors.initials: M
authors.lastname: Reni
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000627:therapeutic use; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004149:Dioxoles / Q000008:administration & dosage* / Q000627:therapeutic use; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011379:Prognosis; D011446:Prospective Studies; D016879:Salvage Therapy / Q000379:methods*; D015996:Survival Rate; D044005:Tetrahydroisoquinolines / Q000008:administration & dosage* / Q000627:therapeutic use; D000077606:Trabectedin; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D018906:Antineoplastic Agents, Alkylating; D004149:Dioxoles; D044005:Tetrahydroisoquinolines; D003841:Deoxycytidine; D000077606:Trabectedin; D000093542:Gemcitabine
keywords: Gemcitabine-resistant chemotherapy; Inflammatory modulation; Metastatic disease; Pancreatic cancer; Salvage treatment; Trabectedin