Safety and tolerability profile of raltitrexed in Chinese patients with locally advanced or recurrent and metastatic colorectal cancer: A phase IV trial.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 571-571
Author(s):  
Shukui Qin ◽  
Jin Li ◽  
Yunpeng Liu ◽  
Yin Chen ◽  
Nong Xu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Locally Advanced ◽  
Chinese Patients ◽  
Tolerability Profile ◽  
Second Line ◽  
Line Therapy ◽  
Third Line Therapy ◽  
Third Line ◽  
Phase Iv

571 Background: The clinical benefit and safety profile associated with raltitrexed in patients with advanced colorectal cancer (CRC) were established. However, safety information of raltitrexed in Chinese patients is rare. We aimed to assess the safety of raltitrexed monotherapy in Chinese patients with advanced CRC. Methods: This single-arm, open-label, multi-center, phase IV trial was conducted in 13 hospitals across China between March 2011 and July 2014. Patients with locally advanced or recurrent and metastatic colorectal cancer (mCRC) received raltitrexed (3mg/m2) as a 15-min infusion on day 1, every 21 days. Treatment was continued until disease progression or unacceptable toxicity. The primary objective was safety and the secondary objectives were disease control rate (DCR), progression free survival (PFS) and overall survival (OS). Results: A total of 215 patients were enrolled, and the safety was assessed in 205 patients. 92 patients had 394 Adverse events (AEs) during the study. A majority (94.4%) of AEs was grade 1/2 and only 5.3% was grade 3/4. Most AEs were either resolved spontaneously or treated successfully with standard medical interventions. Severe AEs were reported by 5.8% (12/205) of patients. The most commonly reported AEs were increase of transaminases, leukopenia, nausea and vomiting. Serum transaminase elevation, an important safety concern associated with raltitrexed therapy, were transient, self-limiting and manageable. No deaths were reported during the study. The DCR in second-line and third-line therapy by raltitrexed reached 49.5% and 37.4%, respectively. The median PFS in second-line and third-line therapy was 1.43 months and 1.47 months, respectively. The median OS was 13.6 months and 8.9 months, respectively. Conclusions: Raltitrexed monotherapy is a safe, well-tolerated and convenient therapy option for Chinese patients. The treatment-associated toxicity is manageable and does not lead to discontinuation of treatment in oncology practice.

scholarly journals Efficacy and safety of regorafenib as beyond second-line therapy in patients with metastatic colorectal cancer: an adjusted indirect meta-analysis and systematic review

2020 ◽  
Vol 12 ◽  
pp. 175883592094093
Author(s):  
Yinying Wu ◽  
Yangwei Fan ◽  
Danfeng Dong ◽  
Xuyuan Dong ◽  
Yuan Hu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Meta Analysis ◽  
Objective Response ◽  
Cochrane Library ◽  
Second Line ◽  
Efficacy And Safety ◽  
Line Therapy ◽  
Third Line Therapy ◽  
Third Line

Background: The evidence base for optimum third-line therapy for metastatic colorectal cancer (mCRC) is not conclusive. Recent studies have demonstrated the efficacy of regorafenib as third-line therapy in mCRC. This indirect meta-analysis compared the efficacy and safety of regorafenib with other available third-line therapies for mCRC. Methods: A literature search for randomized controlled trials (RCTs) was conducted in PubMed, Embase, and Cochrane Library for studies evaluating the efficacy and safety of fruquintinib, regorafenib, TAS-102, and nintedanib as third-line therapies in patients with mCRC. Overall survival (OS) and progression-free survival (PFS) were the primary outcomes, while objective response rate (ORR) and safety were the secondary outcomes. Hazard ratio (HR) and relative risk (RR) with their respective 95% confidence interval (CI) were used for analysis of survival, clinical response, and safety data. An adjusted indirect meta-analysis with placebo as the common comparator was performed. Results: We identified eight RCTs comparing regorafenib (two studies), fruquintinib (two studies), TAS-102 (three studies), and nintedanib (one study) against placebo. The OS with regorafenib was significantly better when compared with nintedanib (HR = 0.66; 95% CI: 0.45, 0.95, p = 0.02) but was similar to that of fruquintinib (HR = 1.01; 95% CI: 0.67, 1.52, p = 0.94) and TAS-102 (HR = 0.97; 95% CI: 0.68, 1.38, p = 0.88). The PFS and ORR for regorafenib were slightly better than those of TAS-102 (PFS: HR = 0.86, 95% CI: 0.54, 1.37, p = 0.5; ORR: RR = 1.13, 95% CI: 0.11, 11.05, p = 0.92) and nintedanib (PFS: HR = 0.68, 95% CI: 0.42, 1.10, p = 0.12; ORR: not reported) but were lower than those for fruquintinib (PFS: HR = 1.53, 95% CI: 0.93, 2.52, p = 0.08; ORR: RR = 0.68269, 95% CI: 0.045, 10.32, p = 0.79). Safety analysis showed that the RR of adverse events (AEs) was lesser in patients treated with regorafenib in comparison with that in patients treated with fruquintinib, but was similar to that in patients treated with nintedanib and TAS-102. Conclusion: Regorafenib has efficacy similar to that of TAS-102 and better safety when compared with fruquintinib. Considering the mechanism of action of regorafenib, which targets multiple factors in the angiogenic pathway, it could be an ideal option for treatment in the beyond second-line setting.

scholarly journals Appropriateness of trifluridine/tipiracil in the clinical practice of third-line therapy in metastatic colorectal cancer

2021 ◽  
Author(s):  
Carlo Barone ◽  
Maria Di Bartolomeo ◽  
Sara Lonardi ◽  
Evaristo Maiello ◽  
Erika Martinelli ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Daily Practice ◽  
Rand Corporation ◽  
Median Score ◽  
Second Line ◽  
Line Therapy ◽  
Clinical Scenarios ◽  
Third Line Therapy ◽  
Third Line

Aim: To help to remove misperception of an appropriate position of trifluridine/tipiracil (FTD/TPI) in the treatment of metastatic colorectal cancer. Materials & methods: The RAND Corporation/UCLA Appropriateness Method was used by a panel of Italian experts to develop recommendations concerning daily practice with FTD/TPI. Forty-three clinical scenarios were discussed in two rounds and the resulting statements were rated as appropriate, uncertain or inappropriate, according to the median score. Results: Several topics were dealt with, covering the profile of eligible patients, therapeutic options beyond the second line, the practice of treatment with FTD/TPI, evaluation and efficacy and toxicity, as well as costs and compliance. Conclusion: FTD/TPI is an important therapeutic resource in refractory metastatic colorectal cancer that combines manageability and safety.

scholarly journals Disease characteristics and treatment patterns of Chinese patients with colorectal cancer: a retrospective study using medical records from China

2019 ◽  
Author(s):  
Ruihua Xu ◽  
Wei Wang ◽  
Bo Zhu ◽  
Xiaoyan Lin ◽  
Dong Ma ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Medical Records ◽  
Large Scale ◽  
Chinese Patients ◽  
Line Treatment ◽  
Second Line ◽  
The Third ◽  
Line Therapy ◽  
Third Line Therapy ◽  
Third Line

Abstract Abstract Background: Colorectal cancer (CRC) is the third most prevalent cancer in China but few large-scale studies were conducted to understand CRC patients. The current study is aimed to gain a real-world perspectives of CRC patients in China. Methods: Using electronic medical records of sampled patients between 2011 and 2016 from 12 hospitals in China, a retrospective cohort study was conducted to describe demographics and disease prognosis of CRC patients, and examine treatment sequences among metastatic CRC (mCRC) patients. Descriptive, comparative and survival analyses were conducted. Results: Of 8,136 CRC patients, 44% had mCRC. Risks of recurrence after radical surgery increased with tumor, models and metastases (TNM) stage at diagnosis (p<0.001). Among mCRC patients, fluorouracil, leucovorin, and oxaliplatin (FOLFOX) and other oxaliplatin-based regimens were the most widely-used first-line treatment (42%). Fluorouracil, leucovorin, irinotecan (FOLFIRI) and other irinotecan-based regimens dominated the second-line (40%). There was no a dominated regimen for the third-line. The proportion of patients receiving chemotherapy with targeted biologics increased from less than 20% for the first- and second- lines to 34% for the third-line (p<0.001). The most common sequence from first- to second-line was from FOLFOX and other oxaliplatin-based regimens to FOLFIRI and other irinotecan-based regimens (286/1,200, 24%). Conclusions: As the only nationwide large-scale study among CRC and mCRC patients before more CRC biologics became available in China in 2017 and 2018, our study reported limited numbers of patients using targeted biologics and no a dominant choice for the third-line therapy. Our findings reflected a lack of consensus on the choice of third-line therapy and limited available options in China. It is evident o continue promoting early CRC diagnosis and to increase the accessibility of treatment options for mCRC patients. Our results can also be used as the baseline to assess treatment pattern changes before and after the inclusion of more third-line treatment were approved and covered into the National Health Insurance Plan in China between 2017 - 2018.

Efficacy and safety of regorafenib as third-line therapy in metastatic colorectal cancer: An indirect meta-analysis.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 119-119
Author(s):  
Yinying WU ◽  
Yangwei Fan ◽  
Dan Feng Dong ◽  
Xuyuan Dong ◽  
Yuan Hu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Relative Risk ◽  
Metastatic Colorectal Cancer ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Secondary Outcome ◽  
Efficacy And Safety ◽  
Line Therapy ◽  
Third Line Therapy ◽  
Third Line

119 Background: The evidence base for optimum third-line therapy for metastatic colorectal cancer (mCRC) is not conclusive. Recent studies have demonstrated the efficacy of regorafenib as third-line therapy in mCRC. This indirect meta-analysis compared the efficacy and safety of regorafenib in comparison to other available third-line therapies in mCRC. Methods: Literature search for randomized controlled trials was conducted in PubMed, Embase and Cochrane library for studies evaluating the efficacy and safety of fruquintinib, regorafenib, TAS-102 and nintedanib as third-line therapies in mCRC patients. The primary outcomes included overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) and safety as the secondary outcome. Hazard ratio (HR) and relative risk (RR) with their respective 95% confidence interval (CI) were used for analysis of survival, clinical response and safety data, respectively. An adjusted indirect meta-analysis with placebo as the common comparator was performed. Results: We identified 8 RCTs studies comparing regorafenib (2 studies), fruquintinib (2 studies), TAS-102 (3 studies) and nintedanib (1 study) against placebo. The OS with regorafenib was significantly better when compared to nintedanib (HR= 0.66, 95% CI 0.45, 0.95, p=0.02), but was similar to that of fruquintinib (HR=1.01, 95% CI 0.67, 1.52, p=0.94) and TAS-102 (HR= 0.97, 95% CI 0.68, 1.38, p=0.88). The PFS and ORR for regorafenib were slightly better than TAS-102 (PFS: HR= 0.86, 95% CI 0.54, 1.37, p=0.5; ORR: RR= 1.13, 95% CI 0.11, 11.05, p=0.92) and nintedanib (PFS: HR= 0.68, 95% CI 0.42, 1.10, p=0.12, ORR: not reported) but was lower than fruquintinib (PFS: HR= 1.53, 95% CI 0.93, 2.52, p=0.08; ORR: RR= 0.68269, 95% CI 0.045, 10.32, p=0.79). Safety analysis showed that the relative risk of adverse events was lesser in patients treated with regorafenib in comparison to fruquintinib but was similar to that of nintedanib and TAS-102. Conclusions: Regorafenib with its efficacy and safety coupled with comprehensive continuously anti-angiogenic therapy, might be the first option in third-line mCRC. Head-on comparisons are required for further validation.

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