title: Off-target effects and clinical outcome in metastatic colorectal cancer patients receiving regorafenib: The TRIBUTE analysis.
abstract: Regorafenib is an orally administered multikinase inhibitor indicated for the treatment of heavily pretreated metastatic colorectal cancer patients with good performance status, albeit less than 50% treated patients achieve disease stabilisation or better at the first radiological evaluation. In addition to that a particularly broad spectrum of toxicities (experienced as G3 or more NCI CTCAE graded by 50% of patients treated) have led to reconsider its widespread use in the majority of patients. We retrospectively collected data about the magnitude of off-target effects experienced during the first 8-weeks of regorafenib monotherapy and analysed their correlation with overall survival, progression free survival and disease control rate. Our findings suggest that skin rash (Exp (B): 0.52, p = 0.0133) or hypothyroidism (Exp (B): 0.11, p = 0.0349) were significantly correlated with improved overall survival at multivariate regression analysis. It was also demonstrated a statistically significant role of diarrhea as predictor of improved survival but its independent prognostic role was lost at multivariate analysis (Exp (B): 0.63, p = 0.162). This is the first analysis showing a potential correlation between the onset of these forms of side effects and regorafenib efficacy, however sample size limitations and the retrospective nature of our analysis prevent us from drawing definitive conclusions.
authors.affiliation: Medical Oncology, University Hospital and Polytechnic University of the Marche, Ancona Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Giampieri
authors.affiliation: Medical Oncology, University Hospital and Polytechnic University of the Marche, Ancona Italy.
authors.forename: Michela Del
authors.initials: MD
authors.lastname: Prete
authors.affiliation: Fondazione Poliambulanza Hospital, Brescia, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Prochilo
authors.affiliation: Medical Oncology, University Hospital and University of Cagliari, Cagliari, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Puzzoni
authors.affiliation: Medical Oncology, University Hospital and University of Cagliari, Cagliari, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Pusceddu
authors.affiliation: Endocrinology Unit, University Hospital and University of Cagliari, Cagliari, Italy.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Pani
authors.affiliation: Medical Oncology, University Hospital and Polytechnic University of the Marche, Ancona Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Maccaroni
authors.affiliation: Medical Oncology, University Hospital and University of Cagliari, Cagliari, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Mascia
authors.affiliation: Medical Oncology, University Hospital and Polytechnic University of the Marche, Ancona Italy.
authors.forename: Maria Giuditta
authors.initials: MG
authors.lastname: Baleani
authors.affiliation: Medical Oncology, University Hospital and Polytechnic University of the Marche, Ancona Italy.
authors.forename: Tania
authors.initials: T
authors.lastname: Meletani
authors.affiliation: Medical Oncology, University Hospital and Polytechnic University of the Marche, Ancona Italy.
authors.forename: Rossana
authors.initials: R
authors.lastname: Berardi
authors.affiliation: Medical Oncology, Azienda Ospedaliera "Brotzu" Cagliari, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Lanzillo
authors.affiliation: Endocrinology Unit, University Hospital and University of Cagliari, Cagliari, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Mariotti
authors.affiliation: Fondazione Poliambulanza Hospital, Brescia, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Zaniboni
authors.affiliation: Medical Oncology, University Hospital and University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Cascinu
authors.affiliation: Medical Oncology, University Hospital and University of Cagliari, Cagliari, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Scartozzi
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D003967:Diarrhea / Q000453:epidemiology; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology* / Q000473:pathology*; D005076:Exanthema / Q000453:epidemiology; D005260:Female; D006801:Humans; D007037:Hypothyroidism / Q000453:epidemiology; D008297:Male; D010671:Phenylurea Compounds / Q000008:administration & dosage* / Q000009:adverse effects*; D011725:Pyridines / Q000008:administration & dosage* / Q000009:adverse effects*; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D011725:Pyridines; C559147:regorafenib