1. Off-target effects and clinical outcome in metastatic colorectal cancer patients receiving regorafenib: The TRIBUTE analysis
- Author
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Fabiana Pani, Stefano Mariotti, Marco Puzzoni, Tania Meletani, Mario Scartozzi, Maria Giuditta Baleani, Stefano Cascinu, Michela Del Prete, Valeria Pusceddu, Riccardo Giampieri, Tiziana Prochilo, Alberto Zaniboni, R. Mascia, Elena Maccaroni, Rossana Berardi, Anna Maria Lanzillo, Giampieri, R., Prete, M. D., Prochilo, T., Puzzoni, M., Pusceddu, V., Pani, F., Maccaroni, E., Mascia, R., Baleani, M. G., Meletani, T., Berardi, R., Lanzillo, A. M., Mariotti, S., Zaniboni, A., Cascinu, S., and Scartozzi, M.
- Subjects
0301 basic medicine ,Oncology ,Diarrhea ,Male ,medicine.medical_specialty ,Multivariate analysis ,Drug-Related Side Effects and Adverse Reactions ,Colorectal cancer ,Pyridines ,Antineoplastic Agents ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Hypothyroidism ,Internal medicine ,Regorafenib ,medicine ,Humans ,Progression-free survival ,Survival analysis ,Aged ,Retrospective Studies ,Multidisciplinary ,Performance status ,business.industry ,Phenylurea Compounds ,Retrospective cohort study ,Exanthema ,medicine.disease ,Rash ,Survival Analysis ,030104 developmental biology ,Treatment Outcome ,chemistry ,030220 oncology & carcinogenesis ,Female ,medicine.symptom ,business ,Colorectal Neoplasms - 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.
- Published
- 2017