Andrea Casadei-Gardini1, Roberto Filippi2,3, Margherita Rimini4, Ilario Giovanni Rapposelli5, Lorenzo Fornaro6, Nicola Silvestris7,8, Luca Aldrighetti9, Giacomo Aimar2,10, Giulia Rovesti4, Giulia Bartolini5, Caterina Vivaldi6, Oronzo Brunetti7, Elisa Sperti11, Rosa La Face2,3, Francesca Ratti9, Kalliopi Andrikou4, Martina Valgiusti5, Laura Bernardini6, Antonella Argentiero7, Elisabetta Fenocchio12, Giovanni Luca Frassineti5, Silvia Cesario6, Francesco Giovannelli8, Virginia Quarà2,10, Francesco Leone13, Stefano Cascinu14. 1. IRCCS San Raffaele Scientific Institute Hospital, Milan, Italy, casadeigardini@gmail.com. 2. Department of Oncology, University of Turin, Turin, Italy. 3. Centro Oncologico Ematologico Subalpino, AOU Città della Salute e della Scienza di Torino, Turin, Italy. 4. Unit of Oncology, Department of Oncology, University Hospital of Modena and Reggio Emilia, Modena, Italy. 5. Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. 6. U.O. Oncologia Medica 2 Universitaria Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy. 7. IRCCS Istituto Tumori "Giovanni Paolo II", Bari, Italy. 8. Department of Biomedical Sciences and Human Oncology, University of Bari "Aldo Moro", Bari, Italy. 9. Hepatobiliary Surgery Division, IRCCS San Raffaele Hospital, Milan, Italy. 10. Division of Medical Oncology, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy. 11. Division of Medical Oncology, Ordine Mauriziano Hospital, Turin, Italy. 12. Multidisciplinary Outpatient Oncology Clinic, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy. 13. Department of Oncology, Azienda Sanitaria Locale di Biella, Ponderano, Italy. 14. IRCCS San Raffaele Scientific Institute Hospital, Milan, Italy.
Abstract
BACKGROUND AND AIMS: In the last few years, there has been increasing interest in non-cancer medications and their potential anti-cancer activity. Data are not available in cholangiocarcinoma (CCA) patients. The aim of this study is to fill this gap by investigating the potential impact in terms of clinical outcome of the common non-cancer medications. METHODS: All consecutive patients with CCAs were retrospectively identified from 7 Italian medical institutions. We investigated the role of intake of vitamin D, aspirin, metformin, statins, and diuretics. RESULTS: A total of 537 patients with CCAs were identified; 197 patients undergoing surgery were evaluated for disease-free survival (DFS), and 509 patients with an advanced stage were evaluated for overall survival (OS). A longer DFS was found in patients with intake of vitamin D versus never users (HR 0.55, 95% CI 0.32-0.92, p = 0.02). In an advanced stage an association with OS was found in patients with intake of metformin versus never users (HR 0.70, 95% CI 0.52-0.93, p = 0.0162), and in patients who have started taking metformin after chemotherapy versus before chemotherapy and never users (HR 0.44, 95% CI 0.26-0.73, p = 0.0016). CONCLUSIONS: Our results highlighted that vitamin D intake improves DFS in patients undergoing surgery. Metformin intake after starting chemotherapy can improve the clinical outcome in advanced disease. These results could open up new therapeutic strategies in cholangiocarcinoma patients. We are planning to undertake a prospective study to validate these data.
BACKGROUND AND AIMS: In the last few years, there has been increasing interest in non-cancer medications and their potential anti-cancer activity. Data are not available in cholangiocarcinoma (CCA) patients. The aim of this study is to fill this gap by investigating the potential impact in terms of clinical outcome of the common non-cancer medications. METHODS: All consecutive patients with CCAs were retrospectively identified from 7 Italian medical institutions. We investigated the role of intake of vitamin D, aspirin, metformin, statins, and diuretics. RESULTS: A total of 537 patients with CCAs were identified; 197 patients undergoing surgery were evaluated for disease-free survival (DFS), and 509 patients with an advanced stage were evaluated for overall survival (OS). A longer DFS was found in patients with intake of vitamin D versus never users (HR 0.55, 95% CI 0.32-0.92, p = 0.02). In an advanced stage an association with OS was found in patients with intake of metformin versus never users (HR 0.70, 95% CI 0.52-0.93, p = 0.0162), and in patients who have started taking metformin after chemotherapy versus before chemotherapy and never users (HR 0.44, 95% CI 0.26-0.73, p = 0.0016). CONCLUSIONS: Our results highlighted that vitamin D intake improves DFS in patients undergoing surgery. Metformin intake after starting chemotherapy can improve the clinical outcome in advanced disease. These results could open up new therapeutic strategies in cholangiocarcinomapatients. We are planning to undertake a prospective study to validate these data.