Factors Affecting the Efficacy of Regorafenib in Metastatic Colorectal Cancer: Is Tumour Sidedness Important?

OBJECTIVE: To investigate the outcomes of regorafenib treatment in refractory metastatic colorectal cancer (mCRC) patients by primary tumour sidedness, the effects of previously targeted therapies, RAS status and inflammatory markers. STUDY DESIGN: Observational study. Place and Duration of the Study: Department of Medical Oncology, Karadeniz Technical University, Faculty of Medicine, Trabzon, Turkey, between January 2012 and September 2020. METHODOLOGY: Clinical data of 102 mCRC patients treated with regorafenib were compared according to the right and left colon subgroups, in terms of factors affecting outcomes of regorafenib treatment. Kaplan-Meier method was used to identify factors associated with the overall survival. RESULTS: Disease control rate (DCR) with regorafenib were similar in both right and left-sided colon tumours (60% vs. 61%, respectively, p>0.99). The median overall survival (OS) was 6.6 months in patients with right-sided colon cancers and 10.1 months in patients with left-sided colon cancers, but it was not significant (p=0.238). When evaluating by RAS status, there was an increase in favour of the right-sided mCRC in progression-free survival and OS, without statistical significance. In multivariate analysis, the patients with metastatic sites <3 and the number of prior systemic therapies ≤3 line had significantly higher survival. CONCLUSION: The tumour burden affected the response to regorafenib in subsequent treatments and regorafenib was also effective in heavily treated mCRC patients. There was no difference in PFS and OS in terms of tumour sidedness by regorafenib treatment. KEY WORDS: Colorectal cancer, Regorafenib, Tumour sidedness.

Clinical outcomes of concomitant use of proton pump inhibitors and regorafenib in patients with metastatic colorectal cancer: a multicenter study.

AIM: To compare survival outcomes, response rates, and adverse events (AEs) in proton pump inhibitor (PPI) user and non-user patients with metastatic colorectal cancer (mCRC) treated with regorafenib. METHODS: We included 272 patients with mCRC treated with regorafenib in this study. Patients were divided into two categories according to their status of PPI use. The primary endpoint was overall survival (OS). The secondary endpoints were time to treatment failure (TTF), response rates, and safety. To exclude immortal time bias in survival analyses, we compared PPI non-user patients and all patients. RESULTS: There were 141 and 131 patients in the PPI non-user and user groups. Baseline characteristics were similar in each group. Pantoprazole was the most used PPI. At the median 35.2 (95% confidence interval (CI): 32.6-37.9) months follow-up, the median OS was similar in PPI non-user and all patients (6.9 months (95% CI: 5.3-8.5) and 7.7 months (95% CI:6.6-8.8), p = 0.913). TTF was also similar in PPI non-user and all patients (3.3 months (95% CI: 2.7-3.9) and 3.5 months (95% CI: 3.0-4.0), p = 0.661). In multivariable analysis, no statistically significant difference was observed between PPI user and non-user groups in OS and TTF (hazard ratio (HR), 0.99; 95% CI, 0.77-1.28; p = 0.963 for OS; HR, 0.93; 0.77-1.20, p = 0.598 for TTF). The objective response rates (ORR) were similar in the PPI non-user and user groups (19.8% and 16.8%, p = 0.455). The rates of any grade AEs were also similar in each group. CONCLUSION: This study found no worse outcome in the combined use of PPI and regorafenib among patients with mCRC.

The relationship between albumin-bilirubin score and survival in patients operated for pancreatic cancer.

Objective: To investigate whether albumin-bilirubin score can be used as a prognostic marker in pancreatic cancer patients post-surgery. METHODS: The retrospective study was conducted at the Medical Oncology Clinic, Karadeniz Technical University, Trabzon, Turkey, and comprised data from 2010 to 2018 of pancreatic cancer patients who had undergone distal pancreatectomy or pancreaticoduodenectomy and were followed up for 3 years. Preoperative and postoperative serum albumin, carcinoembryonic antigen, carbohydrate antigen 19-9, bilirubin, neutrophil:lymphocyte ratio and platelet:lymphocyte ratio were compared as inflammation markers, while albumin-bilirubin scores were calculated using the equation linear predictor. Data was analysed using SPSS 17. RESULTS: Of the 39 patients, 23(59%) were men and 16(41%) were women. The mean age of the sample was 62.4±10.2 years. No statistically significant changes were observed between preoperative and postoperative albumin-bilirubin scores, carcinoembryonic antigen, neutrophil:lymphocyte ratio and platelet:lymphocyte ratio (p>0.05). Significant decreases were observed in postoperative carbohydrate antigen 19-9, aspartate transaminase and alanine transaminas levels (respectively<0.05). No significant change was determined in postoperative albumin-bilirubin grade distributions compared to preoperative values (p=0.180). Although the rate of recurrence increased in line with preoperative albumin-bilirubin scores, the finding was not statistically significant (p=0.055). Mortality rate increased significantly in line with preoperative albumin-bilirubin scores (p=0.013). CONCLUSIONS: The albumin-bilirubin score affected survival in patients with pancreatic cancer, and can be employed as a prognostic factor in this patient group.

Hearing Loss After the First Low Dose Administration of Cisplatin.

Cisplatin is commonly used antineoplastic drug that is effective against different types of tumours. Nephrotoxicity, neurotoxicity, and ototoxicity constitute the main dose-limiting side effects of the drug. We present a case of sensorineural hearing loss after the first low dose of cisplatin. Five days after receiving an intravenous 30 mg/day at 120 minutes, the patient presented with serious bilateral sensorineural hearing loss. Cisplatin-induced hearing impairment is generally dose-related and cumulative; however, the toxicity can occur after the first dose without a cumulative high-dose and can be irreversible. Key Words: Cisplatin, Hearing Loss, Ototoxicity.