Off-target effects and clinical outcome in metastatic colorectal cancer patients receiving regorafenib: The TRIBUTE analysis

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 conclusion

Optimal management of resected gastric cancer

Riccardo Giampieri, Michela Del Prete, Luca Cantini, Maria Giuditta Baleani, Alessandro Bittoni, Elena Maccaroni, Rossana Berardi Oncology Clinic, AOU Ospedali Riuniti, Università Politecnica delle Marche, Ancona, Italy Abstract: Although advances in medical treatment for gastric cancer (GC) have been made, surgery remains the mainstay of cure for patients with localized disease. Improvement in surgical modalities leads to increased chance of cure for resected patients, but a non-negligible number of patients eventually relapse. On this basis, it has been hypothesized that the addition of complementary systemic or local treatments (such as chemotherapy and radiotherapy) could help in improving patients’ survival by reducing the risk of recurrence. Several studies have tried to identify the best approach in localized GC: some of them have assessed the role of perioperative chemotherapy [CT] with different drug combinations, while others have focused on the benefit obtained by addition of radiotherapy, whose role is still under investigation. In particular, the role of chemoradiotherapy, both in adjuvant and neoadjuvant settings, is still uncertain. In the last few years, several clinicopathological and molecular factors have been investigated and identified as potential prognostic markers in GC. Many of these factors could have influenced the outcome of patients receiving combined treatments in the abovementioned studies. Patients have not been generally distinguished by the site of disease (esophageal, gastric and junctional cancers) and surgical approach, making data difficult to be interpreted. The purpose of this review was to shed light on these highly controversial topics. Keywords: gastric cancer, chemotherapy, radiotherapy, adjuvant, neoadjuvant, prognostic factor