Third, the effect of biweekly TAS\102 with BEV about quality of life was not evaluated

Third, the effect of biweekly TAS\102 with BEV about quality of life was not evaluated. hematological toxicities and hard administration schedules. Here, we Cilofexor evaluated the effectiveness and security of a more easy biweekly TAS\102 plus BEV combination. Methods Individuals with mCRC who have been refractory or intolerant to standard chemotherapies were enrolled. Individuals received biweekly TAS\102 (twice daily on days 1C5, every 2?weeks) with BEV (5mg/kg on day time 1, every 2?weeks). The primary endpoint was progression\free survival rate at 16?weeks (16\w PFS rate). Results From October 2017 to January 2018, 46 individuals were enrolled. The recommended phase II dose was determined to be TAS\102 (70 mg/m2/day time). Of the 44 eligible individuals, the 16\w PFS rate was 40.9% (95% confidence interval, 26.3%C56.8%), and the null hypothesis was rejected ( .0001). Median progression\free survival (PFS) and overall survival were 4.29 months and 10.86 months, respectively. Disease control rate was 59.1%. Common grade 3 or higher adverse events were hypertension (40.9%), neutropenia (15.9%), and leucopenia (15.9%). Summary Biweekly TAS\102 plus BEV showed encouraging antitumor activity with security. Discussion The combination of TAS\102 (trifluridine/tipiracil hydrochloride, also known as Lonsurf) plus BEV has shown encouraging antitumor activity in mCRC [1, 2, 3, 4, 5]. However, TAS\102 plus BEV combination therapy was accompanied by an increase in toxicity. Furthermore, scheduling of the standard routine for TAS\102 plus BEV combination therapy is definitely somewhat complicated, with TAS\102 given by oral administration on days 1C5 and 8C12 in a 4\week cycle and BEV by single intravenous administration every 2?weeks [4, 5]. Here, therefore, we planned this Cilofexor phase Ib/II study of biweekly TAS\102 in combination with BEV with Cilofexor the expectation of comparative efficacy but with less toxicity and a simpler regimen schedule. This multicenter prospective trial of biweekly TAS\102 plus BEVthe BiTS studymet its main endpoint, with PFS at 16?weeks exceeding the prespecified threshold. In previous trials [4, 6], CIN related to TAS\102 was associated with better prognosis, suggesting that avoiding a dose reduction of TAS\102 caused by hematological toxicities and maintaining a higher dose could be beneficial to patients. We therefore conducted a prespecified analysis to evaluate the relationship between CIN and antitumor activity in this study. Prespecified subgroup analyses and the multivariable Cox regression analyses to evaluate factors affecting PFS and overall Mouse monoclonal to SIRT1 survival (OS) showed that age and Eastern Cooperative Oncology Group overall performance status (ECOG PS) affected PFS and that CIN within the first two cycles affected OS (Figs. ?(Figs.11 and ?and22). Open in a separate window Physique 1 Progression\free survival. Open in a separate window Physique 2 Overall survival. Biweekly TAS\102 (days 1C5, every 2?weeks) plus BEV combination showed equivalent efficacy with less toxicity compared with the current routine of TAS\102 (days 1C5 and 8C12 in a 4\week cycle) plus BEV combination [4, 5]. Allowing that it is difficult to draw conclusions from cross\trial comparisons because of differences in study design and patient characteristics, the biweekly TAS\102 plus BEV combination might be considered an Cilofexor alternative option with a simple routine. Trial Information Disease Colorectal malignancy; advanced malignancy Stage of Disease/Treatment Metastatic/advanced Prior Therapy More than two prior regimens Type of Study Phase II, single arm Main Endpoint Progression\free survival rate at 16?weeks Secondary Endpoints Overall survival, progression\free survival, overall response rate, security Additional Details of Endpoints or Study Design Study design: From October 2017 to January 2018, 46 patients were enrolled (6 patients in phase Ib and 40 in phase II). Of these 46 patients, two were excluded from the study assessment because they did not start the protocol treatment. In the phase Ib component, no dose\limiting toxicity (DLT) was observed in the first six patients at dose level 1. Accordingly, the recommended phase II dose (RP2D) was decided to be 5 mg/kg for BEV and 70 mg/m2/day for TAS\102. All patients had received.