scholarly journals Disease Monitoring Using Post-induction Circulating Tumor DNA Analysis Following First-Line Therapy in Patients with Metastatic Colorectal Cancer

2020 ◽  
Vol 26 (15) ◽  
pp. 4010-4017
Author(s):  
Xiaoju Max Ma ◽  
Johanna C. Bendell ◽  
Herbert I. Hurwitz ◽  
Christine Ju ◽  
John J. Lee ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Dna Analysis ◽  
Circulating Tumor Dna ◽  
Disease Monitoring ◽  
First Line ◽  
Post Induction ◽  
First Line Therapy ◽  
Line Therapy ◽  
Tumor Dna

Circulating tumor DNA is capable of monitoring the therapeutic response and resistance in advanced colorectal cancer patients undergoing combined target and chemotherapy.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15524-e15524
Author(s):  
Hua Cao ◽  
Xinyi Liu ◽  
Yixin Chen ◽  
Pan Yang ◽  
Tanxiao Huang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Drug Resistance ◽  
Cancer Patients ◽  
Circulating Tumor Dna ◽  
First Line ◽  
Tissue Samples ◽  
First Line Therapy ◽  
Line Therapy ◽  
Colorectal Cancer Patients ◽  
Tumor Dna

e15524 Background: Colorectal cancer (CRC) is a highly lethal disease worldwide. The majority of patients receiving targeted therapy or chemotherapy develop drug resistance, while its molecular mechanism remains to be elucidated. The plasma circulating tumor DNA (ctDNA) exhibited the potential in identifying gene variations and monitoring drug resistance in CRC treatment. Methods: In this study, we monitored the ctDNA mutational changes in advanced CRC patients underwent first-line therapy with bevacizumab and cetuximab combined with chemotherapy. The mutation spectrum of 43 patients was established by a 605-gene next-generation sequencing (NGS) panel. Results: The baseline measurement shows that genes with the highest mutation frequency were TP53 (74%), APC (58%), KRAS (40%), SYNE1 (33%), LRP1B (23%), TOP1 (23%) and PIK3CA (21%). Mutations in TP53, APC and KRAS were detected in 29 paired plasma and tissue samples with the consistency of 81%, 67% and 42%, respectively. Clinically targetable gene mutations, such as APC, RNF43, SMAD4, BRAD1, KRAS, RAF1, and TP53, were also identified in ctDNA. The overall consistency between ctDNA and tissue samples was 54.6%. Alleviation of mutational burden in BRAF, KRAS, AMER1 and other major driving genes was observed following the first-line therapy. Patients with KRAS and TP53 mutations in tissues appeared to benefit more than the wild-type counterpart. The dynamic change of plasma mutation status was consistent with the tissue tumor burden and was closely correlated with disease progression. Conclusions: ctDNA monitoring is a useful method for molecular genotyping of colorectal cancer patients. Dynamic changes in resistance can be sensitively monitored by gene variation status, which potentially helps to develop treatment strategy.

scholarly journals Efficacy of CapeOX plus Cetuximab Treatment as a First-Line Therapy for Patients with Extended RAS/BRAF/PIK3CA Wild-Type Advanced or Metastatic Colorectal Cancer

2018 ◽  
Vol 9 (22) ◽  
pp. 4092-4098
Author(s):  
Shigeyoshi Iwamoto ◽  
Hiromichi Maeda ◽  
Shoichi Hazama ◽  
Koji Oba ◽  
Naoko Okayama ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Wild Type ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

High-dose, single-agent irinotecan as first-line therapy in the treatment of metastatic colorectal cancer

2002 ◽  
Vol 50 (5) ◽  
pp. 383-391 ◽  
Author(s):  
Ychou M. ◽  
Raoul J. ◽  
Desseigne F. ◽  
Borel C. ◽  
Caroli-Bosc F. ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Single Agent ◽  
High Dose ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

scholarly journals Protocol of the EFFORT study: a prospective study of FOLFIRI plus aflibercept as second-line treatment after progression on FOLFOXIRI plus bevacizumab or during maintenance treatment in patients with unresectable/metastatic colorectal cancer

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Hironaga Satake ◽  
Koji Ando ◽  
Eiji Oki ◽  
Mototsugu Shimokawa ◽  
Akitaka Makiyama ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Free Survival ◽  
First Line Therapy ◽  
Line Therapy

Abstract Background FOLFOXIRI plus bevacizumab is used as a first-line therapy for patients with unresectable or metastatic colorectal cancer. However, there are no clear recommendations for second-line therapy after FOLFOXIRI plus bevacizumab combination. Here, we describe our planning for the EFFORT study to investigate whether FOLFIRI plus aflibercept has efficacy following FOLFOXIRI plus bevacizumab for mCRC. Methods EFFORT is an open-label, multicenter, single arm phase II study to evaluate whether a FOLFIRI plus aflibercept has efficacy following FOLFOXIRI plus bevacizumab for mCRC. Patients with unresectable or metastatic colorectal cancer who received FOLFOXIRI plus bevacizumab as a first-line therapy will receive aflibercept and FOLFIRI (aflibercept 4 mg/kg, irinotecan 150 mg/m2 IV over 90 min, with levofolinate 200 mg/m2 IV over 2 h, followed by fluorouracil 400 mg/m2 bolus and fluorouracil 2400 mg/m2 continuous infusion over 46 h) every 2 weeks on day 1 of each cycle. The primary endpoint is progression-free survival (PFS). To achieve 80% power to show a significant response benefit with a one-sided alpha level of 0.10, assuming a threshold progression-free survival of 3 months and an expected value of at least 5.4 months, we estimated that 32 patients are necessary. Secondary endpoints include overall survival, overall response rate, safety, and exploratory biomarker analysis for differentiating anti-VEGF drug in 2nd-line chemotherapy for unresectable or metastatic colorectal cancer. Discussion This is the first study to investigate whether FOLFIRI plus aflibercept has efficacy following FOLFOXIRI plus bevacizumab for unresectable or metastatic colorectal cancer. Switching to a different type of anti-VEGF drug in second-line therapy after FOLFOXIRI plus bevacizumab appears to be an attractive treatment strategy when considering survival benefit. It is expected that this phase II study will prove the efficacy of this strategy and that a biomarker for drug selection will be discovered. Trial registration Japan Registry of Clinical Trials jRCTs071190003. Registered April 18, 2019.

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