Response to regorafenib at an initial dose of 120 mg as salvage therapy for metastatic colorectal cancer

Osawa, Hiroshi

doi:10.3892/mco.2017.1145

Cited by 25 publications

(27 citation statements)

References 21 publications

(20 reference statements)

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“…424 articles were further excluded because they did not satisfy the inclusion criteria. When carefully reviewed the full texts of the remaining 19 potentially eligible papers, 5 more were not included because of insufficient data ( n = 2) [ 16 , 18 ], different dose of regorafenib ( n = 2) [ 19 , 20 ] and duplication ( n = 1) [ 21 ]. A total of 14 trials were selected for the final analysis.…”

Section: Resultsmentioning

confidence: 99%

Incidence and risk of regorafenib-induced hepatotoxicity

Zhao

2017

Oncotarget

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Regorafenib, an oral multi-kinase inhibitor, has been approved for the treatments of several malignancies. Unlike traditional cytotoxic chemotherapeutic agents, regorafenib therapy often induces a distinct profile of adverse events (AEs) including hepatotoxicity. Here we conducted an up-to-date meta-analysis to assess the incidence and risk of regorafenib related hepatic toxicities. PubMed and Embase database were reviewed from inception to June 2017 for relevant trials. Eligible studies include subjects with solid tumors treated with 160 mg of regorafenib daily during the first three week of each four-week cycle, and adequate safety data reporting the elevation of aspartate transaminase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and bilirubin. Statistical analyses were conducted to calculate the summary incidence and relative risk (RR). A total of 2,213 subjects from 14 trials were included. The incidences of regorafenib-associated all-grade and high-grade hepatotoxicity were: bilirubin elevation: 23% and 5%; AST elevation: 32% and 6%; ALT elevation: 27% and 5%; ALP elevation: 31% and 2%. Regorafenib-treated subjects had a significant increased risk of all-grade (RR = 3.10; 95% CI, 2.22–4.34) and high-grade (RR = 1.74; 95% CI, 1.09–2.80) bilirubin elevation; all-grade (RR = 1.51; 95% CI, 1.13–2.00) and high-grade (RR = 1.79; 95% CI, 1.00–3.22) AST elevation; all-grade (RR = 1.82; 95% CI, 1.25–2.64) and high-grade (RR = 3.07; 95% CI, 1.30–7.22) ALT elevation; and all-grade (RR = 2.11; 95% CI, 1.01–4.40) ALP elevation. Our results suggest that regorafenib is associated with an increased risk of hepatic toxicities. Hepatotoxicity examination at regular intervals should be advised to clinicians.

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Section: Resultsmentioning

confidence: 99%

Incidence and risk of regorafenib-induced hepatotoxicity

Zhao

2017

Oncotarget

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“…in the 120 mg group) with comparable DCR (60.0% in the 160 mg group and 58.3% in the 120 mg group [4]. As the result, the dose of regorafenib administered in the present study will be 120 mg once daily for the first 3 weeks in each 4 week cycle.…”

Section: Discussionmentioning

confidence: 92%

Regorafenib plus FOLFIRI with irinotecan dose escalated according to uridine diphosphate glucuronosyltransferase 1A1 genotyping in previous treated metastatic colorectal cancer patients: study protocol for a randomized controlled trial

Chang

Tsai

et al. 2019

Preprint

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Background Regorafenib is an oral multi-kinase inhibitor for metastatic colorectal cancer (mCRC) previously treated with fluoropyrimidines, irinotecan, oxaliplatin, monoclonal antibodies targeting vascular endothelial growth factor (VEGF), and monoclonal antibodies targeting epidermal growth factor receptor (EGFR). A dose reduction from 160 mg to 120 mg regorafenib reduces regorafenib-associated adverse events (AEs). Dose adjustment of irinotecan in FOLFIRI regimen on basis of individual uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) genotype provides optimal oncological outcomes with acceptable AEs. This study is trying to address the efficacy and safety of dose adjusted combination of regorafenib and FOLFIRI for patients with mCRC. Methods A prospective, multicenter, randomized in a 2:1 ratio, controlled, clinical trial with two parallel arms will be conducted to compare irinotecan dose escalated FOLFIRI according to UGT1A1 genotyping plus 120 mg regorafenib with 120 mg regorafenib alone in previously treated patients with mCRC. The primary endpoint is progression-free survival (PFS) and the secondary endpoints are overall survival (OS), disease control rate (DCR), time to progression (TTP), and duration of treatment (DoT). Safety assessments are recorded as well. Discussion Dose adjustment for regorafenib and irinotecan makes treatment-related AEs tolerable and makes the concomitant treatment practicable. This study will provide initial evidences regarding the efficacy and safety of a new combination of chemotherapy and a targeted agent for mCRC.

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“…A greater proportion of patients requiring a dose reduction was found in the CORRECT, REBECCA, and CONSIGN studies (2,5,4). In a study retrospectively evaluating response to regorafenib at an initial dose of 120 mg, disease control rates at the initial dose of 160 mg and 120 mg of regorafenib were similar (12). Furthermore, patients in an Indian exploratory analysis study were evaluated based on the initial dose of regorafenib received (80, 120, or 160 mg), and no statistically significant difference was found between the three groups for PFS (10).…”

Section: Discussionmentioning

confidence: 97%

Single Center Real Life Experience with Regorafenib in Patients with Metastatic Colorectal Cancer

Eryılmaz¹,

Karaağaç²,

Araz³

et al. 2020

Akd Med J

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Objective: To evaluate the clinical benefit of regorafenib in routine clinical practice. Material and Methods: We retrospectively evaluated the data of 45 metastatic colorectal cancer (mCRC) patients who received regorafenib between January 2016 and November 2018. Results: The median age of all patients was 54 years, and 66.7% of the patients were male. Performance status of 20 patients (44.4%) was 2, whereas in 25 patients (55.6%) it was 0-1. Thirty-six patients (80%) were performed primary tumor resection and KRAS mutation was detected in 53.3% of patients. Regorafenib was started at a dose of 160 mg in all patients, and a dose reduction was observed in 28.9% of patients. Line of regorafenib treatment was 3 rd in 66.7% of patients, whereas in 33.3% of patients it was ≥ 4 th. Best response was progressive disease (46.7%) and stable disease (35.6%). The median progression free survival (PFS) was 3.1 months (95% CI: 2.2-4.0) and overall survival (OS) was 6.4 months (95% CI: 3.2-9.5). Primary tumor resection status and using regorafenib ≥ 4 treatment line were significantly associated with both PFS and OS in multivariate analysis. Conclusion: Regorafenib was associated with survival durations similar to those reported in both randomized controlled trials and in the real-life setting, and was generally well tolerated. Patients who had primary tumor resected and using regorafenib as the ≥ 4 th treatment line (primary resected vs nonresected: PFS: 3.8 vs. 1.6 months, p: 0.006; OS: 6.1 vs. 3.1 months, p: 0.018, 3 rd vs. 4 th or more: PFS: 2.7 vs. 4.6 months, p:0.001; OS: 3.8 vs. 11.4 months, p:0.001) were associated with better PFS and OS. However, in order to explain the better survival with regorafenib in patients with primary tumor resected, this information must be confirmed with further studies.

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Response to regorafenib at an initial dose of 120 mg as salvage therapy for metastatic colorectal cancer

Cited by 25 publications

References 21 publications

Incidence and risk of regorafenib-induced hepatotoxicity

Incidence and risk of regorafenib-induced hepatotoxicity

Regorafenib plus FOLFIRI with irinotecan dose escalated according to uridine diphosphate glucuronosyltransferase 1A1 genotyping in previous treated metastatic colorectal cancer patients: study protocol for a randomized controlled trial

Single Center Real Life Experience with Regorafenib in Patients with Metastatic Colorectal Cancer

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