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Background: TAS-102 improves overall survival (OS) of patients with refractory colorectal cancer (CRC), resulting in median progression-free survival (PFS) of 2.0 months (RECOURSE trial). Subsequently, a combination of TAS-102 and bevacizumab was shown to extend median PFS by 3.7 months. However, approximately half of these patients experience grade 3/4 neutropenia. In this study, we evaluated whether biweekly TAS-102 and bevacizumab therapy has efficacy equal to that of conventional TAS-102 and bevacizumab therapy and whether it reduces adverse hematological effects., Methods: This phase II, investigator-initiated, open-label, single-arm, multicenter study was conducted in Japan. Eligible patients had previously received first- and second-line chemotherapy for metastatic CRC. TAS-102 (35 mg/m 2 ) was given twice daily on days 1-5 and days 15-19 in a 4-week cycle, and bevacizumab (5 mg/kg) was administered by intravenous infusion for 30 min every 2 weeks. The primary end point was progression-free survival (PFS), and secondary end points were time-to-treatment failure (TTF), response rate (RR), OS, and safety., Results: 44 patients with metastatic colorectal cancer were enrolled in this study. Median PFS was 4.6 months (95% confidence interval [95% CI] 3.6-5.3) and median OS was 10.5 months (95% CI 9.6-11.4). A partial response was observed in 2 patients (4.5%, 95% CI 0.4-16.0%). The most common adverse event above grade 3 was neutropenia (7 patients, 15.9%, 95% CI 7.6-29.7%)., Conclusions: Biweekly TAS-102 and bevacizumab therapy as third-line chemotherapy appears as effective as conventional TAS-102 and bevacizumab therapy, and this approach reduces adverse hematological effects., (© 2022. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Background/aim: TAS-102 has led to a significant improvement in overall survival (OS) and progression-free survival (PFS) of patients with metastatic colorectal cancer (mCRC). Neutropenia is the most common adverse event and an important factor impacting chemotherapy continuation. In this retrospective study, factors associated with grade ≥3 neutropenia, that is frequently observed in TAS-102-treated patients, were examined., Patients and Methods: The medical records of 41 patients with CRC who received TAS-102 between October 2014 and June 2017 at the Fukuoka University Hospital were retrospectively reviewed. Response rate, PFS, OS, and adverse events were analyzed using KRAS mutation, administration method, concomitant drug administration, neutrophil-to-lymphocyte ratio (NLR), and Onodera's prognostic nutritional index (Onodera's index) as a stratification factors., Results: Both PFS and OS were significantly higher with TAS-102 plus bevacizumab combination therapy. Biweekly administration (7.1%) was associated with significantly less neutropenia compared to normal administration (44.4%). DCR with biweekly administration was better than that with normal administration, although without statistical significance. No significant difference was observed in OS rates between the biweekly and normal administration regimens; however, the biweekly regimen was associated with significantly prolonged PFS. By multivariate analysis, a significant difference was noted in the Onodera's index for OS and in the administration method and NLR for PFS., Conclusion: Biweekly administration without a change in the drug dose intensity was associated with reduced neutropenia in patients with mCRC. The effects and adverse events of TAS-102 were associated with concomitant drug administration, administration method, and nutritional status., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: TAS-102 improved the overall survival of metastatic colorectal cancer (CRC) patients with a median progression-free survival (PFS) in the RECOURSE trial. Subsequently, the combination of TAS-102 and bevacizumab was shown to extend the median PFS (C-TASK FORCE study). However, the study included patients who received second- and third-line treatment. Our study exclusively examined patients receiving this combination as a third-line treatment to investigate the clinical impact beyond cytotoxic doublets. Methods: This investigator-initiated, open-label, single-arm, multi-centered phase II study was conducted in Japan. Eligible CRC patients were refractory or intolerant to fluoropyrimidine, irinotecan, and oxaliplatin in first- and second-line therapy. TAS-102 (35 mg/m2) was given orally twice daily on days 1–5 and 8–12 in a 4-week cycle, and bevacizumab (5 mg/kg) was administered by intravenous infusion every 2 weeks. The primary endpoint was PFS and the secondary endpoints were time-to-treatment failure, response rate, overall survival (OS), and safety. Results: Between June 2016 and August 2017, 32 patients were enrolled. All patients previously received bevacizumab. The median PFS was 4.5 months; the median overall survival was 9.3 months. Partial response was observed in two patients. The most common adverse events above grade 3 were neutropenia followed by thrombocytopenia. There were no non-hematological adverse events above grade 3 and no treatment-related deaths occurred. Conclusions: This study met its primary endpoint of PFS, which is comparable to the results of the C-TASK FORCE study. The TAS-102 and bevacizumab combination has the potential to be a therapeutic option for third-line treatment of metastatic CRC. [ABSTRACT FROM AUTHOR]

TAS-102 significantly improves overall survival in patients with metastatic colorectal cancer. The most common adverse event of TAS-102 is bone marrow suppression, which leads to neutropenia. The incidence of neutropenia is high, and there is no known effective prevention method. Furthermore, the administration method of TAS-102 is complicated. We reported that neutropenia could be avoided by changing to a simple administration method of TAS-102. [ABSTRACT FROM AUTHOR]