A study of Capecitabine Metronomic Chemotherapy is noninferior to Conventional Chemotherapy as Maintenance Strategy in Responders After Induction Therapy in Metastatic Colorectal Cancer

2020 ◽  
Author(s):  
Min Shi ◽  
Tao Ma ◽  
Wenqi Xi ◽  
Jingling Jiang ◽  
Junwei Wu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Maintenance Treatment ◽  
High Efficiency ◽  
Economic Value ◽  
Metronomic Chemotherapy ◽  
Progression Free Survival ◽  
Conventional Chemotherapy ◽  
Open Label ◽  
Standard Dosage

Abstract Background: The aim of this study is to demonstrate that capecitabine metronomic chemotherapy is non-inferior to capecitabine conventional chemotherapy as maintenance treatment, who have responded to 16-18 weeks first-line chemotherapy in metastatic colorectal cancer (mCRC). Methods: The study design is a prospective, randomized, open label, phase II clinical trial. Those mCRC patients who respond well after 16-18 weeks of standard doublet chemotherapy as induction may enrolled into this study, randomly divided into capecitabine metronomic group or standard dosage group. The duration of disease control after randomization and progression free survival from enrollment are primary endpoints. Meanwhile, the overall survival, safety and quality of life are secondary endpoints. The sample size required to achieve the research objectives of this project is 79 cases in each group. The study recently started on 29-01-2018, and will last for 36 months. Discussion: This project intends to study the efficacy and safety of capecitabine metronomic chemotherapy in the maintenance treatment of advanced colorectal cancer, and to explore the strategy of "low toxicity, high efficiency, economy and individualization" which is suitable for China's national conditions and pharmacoeconomics. It has great clinical application prospects and clear socio-economic value.

scholarly journals Efficacy and Safety of Capecitabine Metronomic Chemotherapy versus Conventional Chemotherapy as Maintenance Strategy in Responders After Induction Therapy in Metastatic Colorectal Cancer

2020 ◽  
Author(s):  
Min Shi ◽  
Tao Ma ◽  
Wenqi Xi ◽  
Jingling Jiang ◽  
Junwei Wu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Maintenance Treatment ◽  
High Efficiency ◽  
Metronomic Chemotherapy ◽  
Progression Free Survival ◽  
Efficacy And Safety ◽  
Conventional Chemotherapy ◽  
Open Label ◽  
Standard Dosage

Abstract Background: The aim of this study is to demonstrate that capecitabine metronomic chemotherapy is non-inferior to capecitabine conventional chemotherapy as maintenance treatment, who have responded to 16-18 weeks first-line chemotherapy in metastatic colorectal cancer (mCRC). Methods: The study design is a prospective, randomized, open label, phase II clinical trial. Those mCRC patients who respond well after 16-18 weeks of standard doublet chemotherapy as induction may enrolled into this study, randomly divided into capecitabine metronomic group or standard dosage group. The duration of disease control after randomization and progression free survival from enrollment are primary endpoints. Meanwhile, the overall survival, safety and quality of life are secondary endpoints. The sample size required to achieve the research objectives of this project is 79 cases in each group. The study recently started on 29-01-2018, and will last for 36 months. Discussion: This project intends to study the efficacy and safety of capecitabine metronomic chemotherapy in the maintenance treatment of advanced colorectal cancer, and to explore the strategy of "low toxicity, high efficiency, economy and individualization" which is suitable for China's national conditions and pharmacoeconomics. It has great clinical application prospects and clear socio-economic value.

scholarly journals Biological-guided Metronomic Chemotherapy as Maintenance Strategy in Responders After Induction Therapy in Metastatic Colorectal Cancer

2019 ◽  
Author(s):  
Min Shi ◽  
Tao Ma ◽  
Wenqi Xi ◽  
Jingling Jiang ◽  
Junwei Wu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Maintenance Treatment ◽  
High Efficiency ◽  
Economic Value ◽  
Metronomic Chemotherapy ◽  
Progression Free Survival ◽  
Open Label ◽  
Standard Dosage ◽  
Primary Endpoints ◽  
Open Label Phase

Abstract Background The aim of this study is to demonstrate that capecitabine metronomic chemotherapy is non-inferior to capecitabine conventional chemotherapy as maintenance treatment, who have responded to 16-18 weeks first-line chemotherapy in metastatic colorectal cancer.Methods The study design is a prospective, randomized, open label, phase II clinical trial. Those mCRC patients who respond well after 16-18 weeks of standard doublet chemotherapy as induction may enrolled into this study, randomly divided into capecitabine metronomic group or standard dosage group. The duration of disease control after randomization and progression free survival from enrollment are primary endpoints. Meanwhile, the overall survival, safety and quality of life are secondary endpoints. The sample size required to achieve the research objectives of this project is 79 cases in each group. The study recently started on 29-01-2018, and will last for 36 months.Discussion This project intends to study the efficacy and safety of capecitabine metronomic chemotherapy in the maintenance treatment of advanced colorectal cancer, and to explore the strategy of "low toxicity, high efficiency, economy and individualization" which is suitable for China's national conditions and pharmacoeconomics. It has great clinical application prospects and clear socio-economic value.

scholarly journals Safety and efficacy of panitumumab in combination with trifluridine/tipiracil for pre-treated patients with unresectable, metastatic colorectal cancer with wild-type RAS: The phase 1/2 APOLLON study

2021 ◽  
Author(s):  
Takeshi Kato ◽  
Yoshinori Kagawa ◽  
Yasutoshi Kuboki ◽  
Makio Gamoh ◽  
Yoshito Komatsu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Therapeutic Option ◽  
Phase 1 ◽  
Progression Free Survival ◽  
Phase 2 ◽  
Wild Type ◽  
Open Label ◽  
Safety And Efficacy ◽  
Multicentre Phase

Abstract Background We aimed to assess the safety and efficacy of combination treatment with panitumumab plus trifluridine/tipiracil (FTD/TPI) in patients with wild-type RAS metastatic colorectal cancer (mCRC) who were refractory/intolerant to standard therapies other than anti-epidermal growth factor receptor therapy. Methods APOLLON was an open-label, multicentre, phase 1/2 trial. In the phase 1 part, 3 + 3 de-escalation design was used to investigate the recommended phase 2 dose (RP2D); all patients in the phase 2 part received the RP2D. The primary endpoint was investigator-assessed progression-free survival (PFS) rate at 6 months. Secondary endpoints included PFS, overall survival (OS), overall response rate (ORR), disease control rate (DCR), time to treatment failure (TTF), and safety. Results Fifty-six patients were enrolled (phase 1, n = 7; phase 2, n = 49) at 25 Japanese centres. No dose-limiting toxicities were observed in patients receiving panitumumab (6 mg/kg every 2 weeks) plus FTD/TPI (35 mg/m2 twice daily; days 1–5 and 8–12 in a 28-day cycle), which became RP2D. PFS rate at 6 months was 33.3% (90% confidence interval [CI] 22.8–45.3). Median PFS, OS, ORR, DCR, and TTF were 5.8 months (95% CI 4.5–6.5), 14.1 months (95% CI 12.2–19.3), 37.0% (95% CI 24.3–51.3), 81.5% (95% CI 68.6–90.8), and 5.8 months (95% CI 4.29–6.21), respectively. Neutrophil count decreased (47.3%) was the most common Grade 3/4 treatment-emergent adverse event. No treatment-related deaths occurred. Conclusion Panitumumab plus FTD/TPI exhibited favourable anti-tumour activity with a manageable safety profile and may be a therapeutic option for pre-treated mCRC patients.

Exploratory biomarker findings from cohort 2 of MODUL: An adaptable, phase 2, signal-seeking trial of fluoropyrimidine + bevacizumab ± atezolizumab maintenance therapy for BRAFwt metastatic colorectal cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3570-3570
Author(s):  
Josep Tabernero ◽  
Axel Grothey ◽  
Dirk Arnold ◽  
Michel Ducreux ◽  
Peter J. O'Dwyer ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Maintenance Treatment ◽  
Predictive Biomarkers ◽  
Experimental Treatment ◽  
Progression Free Survival ◽  
Phase 2 ◽  
First Line ◽  
Tissue Samples ◽  
First Line Therapy

3570 Background: MODUL is an adaptable, phase 2, signal-seeking trial testing novel agents as first-line therapy for predefined subgroups of patients with metastatic colorectal cancer (mCRC). Previously reported findings demonstrated that adding atezolizumab to fluoropyrimidine (FP)/bevacizumab as first-line maintenance treatment after induction with FOLFOX + bevacizumab did not improve efficacy outcomes in BRAFwt mCRC. Given these efficacy results, exploratory assessments on tumour samples were conducted to provide insights into factors that might affect efficacy of maintenance treatment and provide guidance on appropriate therapeutic strategies for BRAFwt mCRC. Methods: In patients with BRAFwt tumours (Cohort 2), experimental treatment was FP/bevacizumab + atezolizumab. Primary efficacy endpoint: progression-free survival (PFS). Overall survival (OS) was a secondary endpoint. Archival tissue samples from 104 patients were analysed by immunohistochemistry (IHC) at HistoGeneX (PD-L1; CD8/GrB/FoxP3). SP142 antibody was used for PD-L1 IHC analysis, which evaluated PD-L1low (IC 0–1) vs PD-L1high (IC > 1) in correlation with PFS and OS in the control and experimental arms. CD8/GrB/FoxP3 triplex staining was also performed to evaluate potential correlations with efficacy. Results: 445 patients with BRAFwt mCRC were randomised (2:1 ratio) to maintenance treatment in Cohort 2. Archival samples from 104 patients were analysed: FP/bevacizumab + atezolizumab (n = 82); FP/bevacizumab (n = 22). The biomarker evaluable population (BEP) for PD-L1 was n = 81 for FP/bevacizumab + atezolizumab [PD-L1low n = 35 (43%); PD-L1high n = 46 (57%)] and n = 22 for FP/bevacizumab [PD-L1low n = 16 (72%); PD-L1high n = 6 (28%)]. The BEP for CD8/GrB was n = 50 for FP/bevacizumab + atezolizumab and n = 16 for FP/bevacizumab. No difference in PFS or OS was observed in the FP/bevacizumab + atezolizumab vs FP/bevacizumab arms for PD-L1high [PFS: HR = 1.5 (95% CI 0.45−4.8), p = 0.51; OS: HR = 1.3 (95% CI 0.38−4.1), p = 0.71] or PD-L1low [PFS: HR = 0.92 (95% CI 0.47−1.8), p = 0.81; OS: HR = 0.78 (95% CI 0.4−1.5), p = 0.48]. Similar results were observed with CD8/GrBhigh [PFS: HR = 0.73 (95% CI 0.27−2.0), p = 0.55; OS: HR = 0.66 (95% CI 0.24−1.8), p = 0.44], CD8/GrBlow [PFS: HR = 1.0 (95% CI 0.42–2.5), p = 0.96; OS: HR = 0.73 (95% CI 0.3–1.8), p = 0.5], FoxP3high [PFS: HR = 0.97 (95% CI 0.37−2.5), p = 0.95; OS: HR = 0.95 (95% CI 0.36−2.5), p = 0.91] and FoxP3low [PFS: HR = 0.73 (95% CI 0.29−1.9), p = 0.53; OS: HR = 0.5 (95% CI 0.19−1.3), p = 0.18]. Conclusions: These findings suggest that PD-L1, CD8/GrB and FoxP3 might not be predictive biomarkers in BRAFwt mCRC. Further analyses are needed to further evaluate potential predictive and prognostic factors of response in this setting. Clinical trial information: NCT02291289.

scholarly journals Cetuximab versus bevacizumab maintenance following prior 8-cycle modified FOLFOXIRI plus cetuximab in Asian postmenopausal women with treatment-naive KRAS and BRAF wild-type metastatic colorectal cancer

2020 ◽  
Vol 48 (9) ◽  
pp. 030006052093044
Author(s):  
Baomin Chen ◽  
Donghua Zheng ◽  
Weiguang Yu ◽  
Cuiping Huang ◽  
Junxing Ye ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Postmenopausal Women ◽  
Induction Therapy ◽  
Maintenance Treatment ◽  
Progression Free Survival ◽  
Wild Type ◽  
Clinical Endpoints ◽  
Treatment Naïve

Objective To assess the efficacy and safety of cetuximab (CE) versus bevacizumab (BE) maintenance treatment after prior 8-cycle modified 5-fluorouracil, folinate, oxaliplatin, and irinotecan (FOLFOXIRI) plus CE induction therapy in treatment-naive KRAS and BRAF wild-type (wt) metastatic colorectal cancer (mCRC). Methods From 2012 to 2017, prospectively maintained databases were reviewed to assess Asian postmenopausal women with treatment-naive KRAS and BRAF wt mCRC who underwent modified FOLFOXIRI plus CE induction therapy, followed by CE or BE maintenance until disease progression or death. Co-primary clinical endpoints were progression-free survival (PFS) and overall survival (OS). Results A total of 222 women were included (CE n = 110 and BE n = 112). At a median follow-up of 27.0 months (interquartile range, 6.5–38.6 months), median PFS was 21.9 months (95% confidence interval [CI] 16.4–24.4) and 17.7 months (95% CI 11.3–19.0) for CE and BE groups, respectively (hazard ratio [HR] 0.31, 95% CI 0.15–0.46); median OS was 26.0 months (95% CI 23.4–28.7) and 22.7 months (95% CI 21.2–24.3) for CE and BE groups, respectively (HR 0.22, 95% CI 0.11–0.37). Conclusions CE maintenance treatment is more poorly tolerated but has a slightly more modest survival benefit compared with BE maintenance treatment in mCRC.

scholarly journals Bevacizumab in combination with fluoropyrimidine-based chemotherapy for the first-line treatment of metastatic colorectal cancer

2010 ◽  
Vol 14 (Suppl 2) ◽  
pp. 47-53
Author(s):  
S Whyte ◽  
A Pandor ◽  
M Stevenson ◽  
A Rees
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Absolute Difference ◽  
First Line ◽  
Open Label ◽  
Open Label Study ◽  
Free Survival

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of bevacizumab in combination with fluoropyrimidine-based chemotherapy for the first-line treatment of metastatic colorectal cancer based on the manufacturer’s submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. Evidence was available in the form of one phase III, multicentre, multinational, randomised, open-label study (NO16966 trial). This two-arm study was originally designed to demonstrate the non-inferiority of oral capecitabine plus oxaliplatin (XELOX) compared with 5-fluorouracil plus folinic acid plus oxaliplatin (FOLFOX)-4 in adult patients with histologically confirmed metastatic colorectal cancer who had not previously been treated. Following randomisation of 634 patients, the open-label study was amended to include a 2 × 2 factorial randomised (partially blinded for bevacizumab) phase III trial with the coprimary objective of demonstrating superiority of bevacizumab in combination with chemotherapy compared with chemotherapy alone. Measured outcomes included overall survival, progression-free survival, response rate, adverse effects of treatment and health-related quality of life. The manufacturer’s primary pooled analysis of superiority (using the intention-to-treat population) showed that after a median follow-up of 28 months, the addition of bevacizumab to chemotherapy significantly improved progression-free survival and overall survival compared with chemotherapy alone in adult patients with histologically confirmed metastatic colorectal cancer who were not previously treated [median progression-free survival 9.4 vs 7.7 months (absolute difference 1.7 months); hazard ratio (HR) 0.79, 97.5% confidence interval (CI) 0.72 to 0.87; p = 0.0001; median overall survival 21.2 vs 18.9 months (absolute difference 2.3 months); HR 0.83, 97.5% CI 0.74 to 0.93; p = 0.0019]. The NO16966 trial was of reasonable methodological quality and demonstrated a significant improvement in both progression-free survival and overall survival when bevacizumab was added to XELOX or FOLFOX. However, the size of the actual treatment effect of bevacizumab is uncertain. The ERG believed that the modelling structure employed was appropriate, but highlighted several key issues and areas of uncertainty. At the time of writing, NICE was yet to issue the guidance for this appraisal.

scholarly journals Safety, efficacy and patient-reported outcomes with trifluridine/tipiracil in pretreated metastatic colorectal cancer: results of the PRECONNECT study

ESMO Open ◽  
2020 ◽  
Vol 5 (3) ◽  
pp. e000698
Author(s):  
Jean-Baptiste Bachet ◽  
Lucjan Wyrwicz ◽  
Timothy Price ◽  
Chiara Cremolini ◽  
Jean-Marc Phelip ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Progression Free Survival ◽  
Open Label ◽  
Patient Reported ◽  
Registration Number ◽  
Grade 3

BackgroundIn RECOURSE (, trifluridine/tipiracil significantly improved overall survival and progression-free survival (PFS) versus placebo in patients with pretreated metastatic colorectal cancer (mCRC). PRECONNECT was designed to further characterise safety and clinical use of trifluridine/tipiracil.MethodsIn this ongoing, international, multicentre, open-label trial, patients with pretreated mCRC received oral trifluridine/tipiracil 35 mg/m2 twice daily on days 1–5 and 8–12 of each 28-day cycle. The primary endpoint was safety; secondary endpoints included PFS and quality of life (QoL).Results793 patients (median age 62 years) from 13 countries received trifluridine/tipiracil for a median of 2.84 months (IQR 2.64). Adverse events (AEs) were experienced by 96.7%; the most common (≥20% of patients) were neutropaenia, asthenia/fatigue, nausea, anaemia and diarrhoea. Grade ≥3 AEs occurred in 73.9% of patients, with the most common being neutropaenia (39.1% of patients), anaemia (9.8%) and asthenia/fatigue (5.0%). Median PFS was 2.8 months (95% CI 2.7 to 2.9). Median time to Eastern Cooperative Oncology Group performance status deterioration (≥2) was 8.9 months (range 0.03–14.72). There was no clinically relevant change from baseline in QoL.ConclusionsPRECONNECT showed consistent results with the previously demonstrated safety and efficacy profile of trifluridine/tipiracil, with no new safety concerns identified. QoL was maintained during treatment.Trial registration numberNCT03306394.

A randomized phase III trial of S-1/oxaliplatin (SOX) plus bevacizumab versus 5-FU/l-LV/oxaliplatin (mFOLFOX6) plus bevacizmab in patients with metastatic colorectal cancer: The SOFT study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3519-3519 ◽  
Author(s):  
Daisuke Takahari ◽  
Yasuhide Yamada ◽  
Hiroshi Matsumoto ◽  
Hideo Baba ◽  
Kazuhiro Yoshida ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Progression Free Survival ◽  
Phase Iii ◽  
P Value ◽  
Open Label ◽  
Phase Iii Trial ◽  
Open Label Phase ◽  
Grade 3 ◽  
Ecog Ps

3519 Background: Several studies of oxaliplatin plus S-1 combination therapy (SOX) conducted in Asia have shown promising efficacy and safety for metastatic colorectal cancer (mCRC), suggesting the potential to replace mFOLFOX6. We performed a randomized phase III trial to determine whether SOX plus bevacizmab (SOX+Bev) is non-inferior to mFOLFOX6 plus bevacizmab (mFOLFOX6+Bev) in terms of progression-free survival (PFS). Methods: The SOFT study was a randomized, open-label, phase III trial. Chemotherapy-naïve patients (pts) with mCRC, an ECOG PS of 0-1, and adequate organ functions were randomized to receive either mFOLFOX6+Bev (5 mg/kg of bevacizumab, followed by 200 mg/m2 of l-leucovorin given simultaneously with 85 mg/m2 of oxaliplatin, followed by a 400 mg/m2 bolus of 5-FU on day 1 and then 2,400 mg/m2 of 5-FU over 46 h, every 2 weeks) or SOX+Bev (7.5 mg/kg of bevacizumab, 130 mg/m2 of oxaliplatin on day 1, and 40−60 mg of S-1 twice daily for 2 weeks, followed by a 1-week rest). The primary endpoint was PFS. A sample size of 225 pts per group was estimated to be necessary based on a median PFS of 10.0 months in each group and an 80% power to demonstrate non-inferiority of SOX+Bev with a 2.5-month margin (hazard ratio, HR = 1.33) and a 2-sided alpha of 0.05. Results: A total of 512 pts were enrolled from February 2009 to March 2011. Data were analyzed after confirming >388 events as planned. Demographic factors were well balanced. Pts received a median of 12 cycles (1 cycle = 2 weeks) of mFOLFOX6+Bev and 8 cycles (1 cycle = 3 weeks) of SOX+Bev (range: 1−16). Median PFS was 11.5 months (95% CI: 10.7−13.2) with mFOLFOX6+Bev and 11.7 months (95% CI: 10.7−12.9) with SOX+Bev. The adjusted HR for PFS was 1.043 (95% CI: 0.860−1.266), and the p value for non-inferiority was 0.0139. Response rate was 62.7% with mFOLFOX6+Bev and 61.5% with SOX+Bev. Grade 3/4 toxicities (%) with mFOLFOX6+Bev/SOX+Bev were leukopenia 8.4/2.4, neutropenia 33.7/8.8, anorexia 1.2/5.2, and diarrhea 2.8/9.2. Conclusions: SOX+Bev is non-inferior to mFOLFOX6+Bev with respect to PFS as 1st-line treatment for mCRC and thus can replace mFOLFOX6+Bev. Clinical trial information: JapicCTI-090699.

Capecitabine, Bevacizumab, and Mitomycin in First-Line Treatment of Metastatic Colorectal Cancer: Results of the Australasian Gastrointestinal Trials Group Randomized Phase III MAX Study

2010 ◽  
Vol 28 (19) ◽  
pp. 3191-3198 ◽  
Author(s):  
Niall C. Tebbutt ◽  
Kate Wilson ◽  
Val J. Gebski ◽  
Michelle M. Cummins ◽  
Diana Zannino ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Open Label ◽  
Free Survival ◽  
Treatment Regimens ◽  
The United Kingdom

Purpose To determine whether adding bevacizumab, with or without mitomycin, to capecitabine monotherapy improves progression-free survival (PFS) in patients with metastatic colorectal cancer (mCRC) in an open-label, three-arm randomized trial. Patients and Methods Overall, 471 patients in Australia, New Zealand, and the United Kingdom with previously untreated, unresectable mCRC were randomly assigned to the following: capecitabine; capecitabine plus bevacizumab (CB); or capecitabine, bevacizumab, and mitomycin (CBM). We compared CB with capecitabine and CBM with capecitabine for progression-free survival (PFS). Secondary end points included overall survival (OS), toxicity, response rate (RR), and quality of life (QOL). Results Median PFS was 5.7 months for capecitabine, 8.5 months for CB, and 8.4 months for CBM (capecitabine v CB: hazard ratio [HR], 0.63; 95% CI, 0.50 to 0.79; P < .001; C v CBM: HR, 0.59; 95% CI, 0.47 to 0.75; P < .001). After a median follow-up of 31 months, median OS was 18.9 months for capecitabine and was 16.4 months for CBM; these data were not significantly different. Toxicity rates were acceptable, and all treatment regimens well tolerated. Bevacizumab toxicities were similar to those in previous studies. Measures of overall QOL were similar in all groups. Conclusion Adding bevacizumab to capecitabine, with or without mitomycin, significantly improves PFS without major additional toxicity or impairment of QOL.

scholarly journals Сonfirmatory study of the efficacy and tolerability of trifluridine/tipiracil (TAS-102) therapy in the Russian population with chemorefractory metastatic colorectal cancer

2020 ◽  
pp. 47-52
Author(s):  
M. Yu. Fedyanin ◽  
F. V. Moiseenko ◽  
D. A. Chekini ◽  
V. A. Chubenko ◽  
A. S. Zhabina ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Survival Rate ◽  
Disease Control ◽  
Metastatic Colorectal Cancer ◽  
Colon Adenocarcinoma ◽  
Progression Free Survival ◽  
Russian Population ◽  
Open Label ◽  
Free Survival ◽  
Efficacy Criteria

Introduction. Trifluridine/Tipiracil (FTD/TPI) is a new chemotherapeutic drug approved in more than 60 countries for use in patients with metastatic colorectal cancer who have registered progression or intolerance to treatment with fluoropyrimidines, oxaliplatin and irinotecan, anti-VEGRand anti-EGFR-targeted agents. This study evaluated for the first time the effectiveness and tolerability of FTD/TPI therapy in the Russian patient population.Materials and methods. A confirmatory open-label single-arm non-randomized trial was conducted in 2 clinical centres in Russia. The main criteria for inclusion were: conduction of at least the 2nd line of standard systemic therapy for metastatic colon adenocarcinoma. The primary efficacy criteria were: 2-month progression-free survival; secondary – median progressionfree survival, disease control frequency, safety assessment, overall survival. Research number: NCT03274882.Results. A total of 26 patients were included in the study; the median age was 60.5 years (30 to 78); 19 (73%) women; and 4 patients with ECOG 0 and 22 – with ECOG 1. All patients were previously treated with the inclusion of oxaliplatin, irinotecan, fluoropyrimidines, 21 (81%) – bevacizumab, 6 (23%) – anti-EGFR antibodies, and 2 (7.7%) – regorafenib. The median for treatment courses was 4 (1–21), 11 (42.3%) patients were treated for 6 months or more. The two-month progression-free survival rate was 52% with a median progreesion-free survival rate of 4 months (95% CI 1.8–7.4 months). The median of total survival rate was 11 months (95% CI 5,2–16,8 months). Disease control was achieved in 60%. Neutropenia, nausea, vomiting, anemia, weakness prevailed among undesirable events associated with treatment (≥5 patients). The majority of complications were of the 1st–2nd degree. Among the undesirable events of the 3rd–4th degree, neutropenia was more common, while in 3 patients febrile neutropenia of the 3rd degree was registered.Conclusions. In the Russian population of patients with colorectal chemorefractory cancer, the drug FTD/TPI (TAS-102) shows efficacy and tolerability comparable to the RECOURSE registration study.

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