Relation between sarcopenia and dose-limiting toxicity in patients with metastatic colorectal cancer who received regorafenib.

BACKGROUND: Sarcopenia is related to poor prognosis and drug toxicities in solid tumors. The aim of our study is to investigate the predisposition of patients with metastatic colorectal carcinoma who started regorafenib treatment to sarcopenia and prolonged survival. METHODS: Patients with metastatic colorectal carcinoma who receives regorafenib were search retrospectively. Dose-limiting toxicity was defined as dose reduction or toxicity requiring drug withdrawal. Sarcopenia evaluation was made with computed tomography performed within a month before treatment. Progression-free survival and overall survival were estimated. RESULTS: Thirty-six patients were found as suitable for the study. 63.9% of patients were found as basally sarcopenic. Dose-limiting toxicity occured 13 of 23 patients (56.5%) with basal sarcopenia, whereas only 1 of 13 patients (7.6%) with no sarcopenia exhibited dose-limiting toxicity (p = 0.005). Three patients suffered from grade 3-4 toxicity. Hand-foot syndrome, hypertension, and mucosal rash were the most seen side effects. Mean regorafenib treatment duration was 3.36 months. There was no significant difference in the progression-free survival (PFS) and the overall survival (OS) between sarcopenic patients and patients with no sarcopenia. Durations were as OS 24.2 weeks in patients with sarcopenia (95% CI 16.7-31.7), 28.1 weeks in patients with no sarcopenia (95% CI 20.5-35.7) (p = 0.36), and as PFS 14.2 weeks in patients with sarcopenia (95% CI 12.1-16.4), 14.8 weeks in patients with no sarcopenia (95% CI 9.7-20.1) (p = 0.65). CONCLUSION: Dose-limiting toxicity was significantly higher in basally sarcopenic patients who were started regorafenib as treatment of metastatic colorectal carcinoma. There was no significant relationship between overall survival and progression-free survival with sarcopenia.

Skeletal muscle loss during anti-EGFR combined chemotherapy regimens predicts poor prognosis in patients with RAS wild metastatic colorectal cancer.

PURPOSE: We aimed to assess whether anti-EGFR combined chemotherapy regimens are related with loss of skeletal muscle mass and to compare cetuximab and panitumumab therapies in the aspect of skeletal muscle area change as well as to assess whether skeletal muscle mass loss has prognostic significance in the RAS wild mCRC patients. MATERIALS AND METHODS: A total of 56 patients (30 patients in cetuximab arm and 26 patients in panitumumab) who had computed tomography images were retrospectively evaluated at the diagnosis and follow up during the treatment period before progression. RESULTS: During treatment period 24 patients (42.8%) had muscle loss. Of these, 7 (29.2%) patients were treated at first-line and 17 (70.8%) patients were treated at second-line setting. There was no significant difference in the aspect of skeletal muscle loss among cetuximab and panitumumab combined treatment regimens. Median PFS was 9.1 (8.6-9.6) months in muscle loss group and 13.9 (7.2-20.6) months in muscle stable group (p = 0.001). Median OS was 23.4 (95% CI 15.8-31.0) months in muscle stable group and 19.1 (95% CI 17.0-21.3) months in muscle loss group (p = 0.57) at first-line setting. For second-line, median OS was 21.2 (14.7-27.7) months in muscle stable group and 14.4 (6.0-22.4) months in muscle loss group (p = 0.003). CONCLUSIONS: Decrease in skeletal muscle mass before progression on CT imaging is an independent indicator for shorter PFS value in RAS WT mCRC patients who received anti-EGFR combined chemotherapy regimens at both the first and second-line settings. Beside that shorter overall survival values also were significantly seen in patients who had muscle loss during anti-EGFR therapy in the second-line setting.