Oral fruquintinib combined with tegafur-gimeracil-oteracil potassium for advanced colorectal cancer to obtain longer progression-free survival:A case report

BACKGROUND After the failure of second-line standard therapy,effective treatment options for metastatic colorectal cancer are limited,and the duration of remission cannot meet clinical needs.In addition,associated drug toxicity may lead to treatment interruption that may affect patient outcomes.Therefore,more safe,effective and convenient treatments are urgently needed.CASE SUMMARY Here,we describe a patient with advanced colorectal cancer with multiple metastases in both lungs.Oxaliplatin combined with 5-fluorouracil or capecitabine was given as the first-line treatment,and bevacizumab combined with irinotecan was given as the second-line treatment after disease progression.However,treatment was interrupted due to recurrent grade 2 nausea and grade 1 diarrhea.He received targeted therapy with fruquintinib starting on August 26,2020 and responded well for 12 mo.After slow progression of the lung metastases,progression-free survival was again achieved over 13.5 mo by continued treatment of fruquintinib in combination with tegafur-gimeracil-oteracil potassium chemotherapy.Overall treatment duration was more than 25.5 mo.The treatments delayed tumor progression,reduced drug side effects,maintained a good quality of life,and further extended overall survival.CONCLUSION This case report detailed preliminary evidence showing that the combination of fruquintinib with tegafur-gimeracil-oteracil potassium chemotherapy double oral therapy may result in longer progression-free survival in patients with advanced colorectal cancer.

Retrospective efficacy analysis of olaparib combined with bevacizumab in the treatment of advanced colorectal cancer

BACKGROUND Colorectal cancer(CRC)is a highly prevalent malignancy of the digestive tract worldwide,characterized by a significant morbidity and mortality rate and subtle initial symptoms.Diarrhea,local abdominal pain,and hematochezia occur with the development of cancer,while systemic symptoms such as anemia and weight loss occur in patients with advanced CRC.Without timely interventions,the disease can have fatal consequences within a short span.The current therapeutic options for colon cancer include olaparib and bevacizumab,which are widely utilized.This study intends to evaluate the clinical efficacy of olaparib combined with bevacizumab in the treatment of advanced CRC,hoping to provide insights into advanced CRC treatment.AIM To investigate the retrospective efficacy of olaparib combined with bevacizumab in the treatment of advanced CRC.METHODS A retrospective analysis was conducted on a cohort of 82 patients with advanced colon cancer who were admitted to the First Affiliated Hospital of the University of South China between January 2018 and October 2019.Among them,43 patients subjected to the classical FOLFOX chemotherapy regimen were selected as the control group,and 39 patients undergoing treatment with olaparib combined with bevacizumab were selected as the observation group.Subsequent to different treatment regimens,the short-term efficacy,time to progression(TTP),and incidence rate of adverse reactions between the two groups were compared.Changes in serum-related indicators[vascular endothelial growth factor(VEGF),matrix metalloprotein-9(MMP-9),cyclooxygenase-2(COX-2)]and tumor markers[human epididymis protein 4(HE4),carbohydrate antigen 125(CA125),carbohydrate antigen 199(CA199)]levels before and after treatment were compared between the two groups at the same time.RESULTS The objective response rate was discovered to be 82.05%,and the disease control rate was 97.44%in the observation group,which were significantly higher than the respective rates of 58.14%and 83.72%in the control group(P<0.05).The median TTP was 24 mo(95%CI:19.987-28.005)in the control group and 37 mo(95%CI:30.854-43.870)in the observation group.The TTP in the observation group was significantly better than that in the control group,and the difference held statistical significance(log-rank test value=5.009,P=0.025).Before treatment,no substantial difference was detected in serum VEGF,MMP-9,and COX-2 levels and tumor markers HE4,CA125,and CA199 levels between the two groups(P>0.05).Following treatment with different regimens,the above indicators in the two groups were remarkably promoted(P<0.05),VEGF,MMP-9,and COX-2 in the observation group were lower than those in the control group(P<0.05),and HE4,CA125,and CA199 levels were also lower than those in the control group(P<0.05).Visà-vis the control group,the total incidence of gastrointestinal reactions,thrombosis,bone marrow suppression,liver and kidney function injury,and other adverse reactions in the observation group was notably lowered,with the difference considered statistically significant(P<0.05).CONCLUSION Olaparib combined with bevacizumab in the treatment of advanced CRC demonstrates a strong clinical effect of delaying disease progression and reducing the serum levels of VEGF,MMP-9,COX-2 and tumor markers HE4,CA125 and CA199.Moreover,given its fewer adverse reactions,it can be regarded as a safe and reliable treatment option.

Predictive and prognostic biomarkers with therapeutic targets in advanced colorectal cancer

Colorectal cancer(CRC)is one of the most common human malignant diseases and the second leading cause of cancer-related deaths worldwide.The treatment of advanced CRC has improved significantly in recent years.With the emergence of two targeted antibodies,cetuximab(Erbitux),an anti-epidermal growth factor receptor monoclonal antibody and bevacizumab(Avastin),a vascular endothelial growth factor monoclonal antibody,the treatment of metastatic CRC has entered the era of personalized therapy.Predictive and prognostic biomarkers have,and will continue to,facilitate the selection of suitable patients and the personalization of treatment for metastatic CRC(mCRC).In this review,we will focus primarily on the important progresses made in the personalized treatment of mCRC and discuss the potentially novel predictive and prognostic biomarkers for improved selection of patients for anti-cancer treatment in the future.

Which strategy after first-line therapy in advanced colorectal cancer?

Second-line therapy for advanced colorectal cancer is an integral part of the treatment strategy that needs to be set from the beginning for each patient, bearing in mind the expected toxicities of chosen treatments, the patient's clinical condition, comorbidities, preferences, the aims of the treatment and the molecular status. Furthermore, the distinction between lines of therapy is no longer absolute. The perspective of "continuum of care" includes switching chemotherapy prior to disease progression, maintenance therapy, drug "holidays" if needed, surgical resection of metastases in selected patients, and seems to allow a tailored treatment, in which patients are more likely to benefit from exposure to all active agents, which is known to correlate with overall survival. The scenario of second-line treatment has changed dramatically over the years and could currently benefit from several options including chemotherapy with a single agent or in combination and the addition of molecular-targeted agents developed in the last decade, such as epidermal growth factor receptor antibodies(cetuximab, panitumumab) and vascular endothelial growth factor-targeting agents(bevacizumab, aflibercept), with the possibility of bevacizumab use even beyond first progression. The purpose of this review is to summarize the most important scientific data supporting the use of chemotherapy and the new biologic agents in the second-line setting in advanced colorectal cancer.

The short-time effects of chemotherapy with combinations of hydroxycamptothecine and oxaliplatin in treatment of advanced colorectal cancer

Objective： Although 5-fluarouracil-based chemotherapy has become a standard regimen for treatment of advanced colorectal cancer, the efficacy, as second line therapy, is not high. It is necessary to find a new regimen as a substitute for these patients. The study was to evaluate the short-time effects and toxicity of combination of HCPT plus L-OHP regimen in treatment of advanced colorectal cancer. Methods： Forty-seven patients with pathological evidence of advanced colorectal cancer were enrolled and were treated with HCPT plus L-OHP regimen for 86 cycles. All patients were treated with L-OHP 130 mg/m^2 day 1 and HCPT 6 mg/m^2day 1-4, the chemotherapy was repeated every 3 weeks as a cycle. The Short-time efficats and side effects were evaluated after 2 cycles for each patient. Results： 38 cases can be evaluated to short-time effects and achieved the overall response rate （CR＋PR） was 36.8%. KPS improved in 20 cases （52.6%）. In the total 86 cycles, the leucopenia occurred in 59 cycles （68.6%）,18 cycles （30.5%） in grade Ⅲ and Ⅳ and the diarrhea occurred in 48 cycles （55.8%）, 18 cycles （37.5%） in grade Ⅲ and Ⅳ. Conclusion： A satisfied response rate was obtained in advanced colorectal cancer patients treated by HCPT plus L-OHP regimen, especially who were the failure of first-line chemotherapy with 5-FU. The limited-dose toxicity was leucopenia and diarrhea.

Nursing of advanced colorectal cancer patients treated with Cetuximab combined with chemotherapy

Cetuximab is a new medication that has recently been approved for the treatment of advanced colorectal cancer. To date we have had little experience in using this targeted agent. Eleven patients in our hospital with advanced colorectal cancer were treated with cetuximab and chemotherapy. Based on the curative effect of this combination therapy, we have concluded that the following nursing practices make an important contribution to the patients＇ prognosis and wellbeing： to establish a good nurse-patient relationship, to increase patient understanding of the side effects, to standardize the medications, to observe and to deal with the side effects of the medications（for example skin reaction, neutropenia, and diarrhea）, and to provide continuous mental health care support and education.

Effect and safety of Kanglaite injection combined with chemotherapy in the treatment of advanced colorectal cancer:a systematic review and meta-analysis

Objective:To evaluate the clinical efficacy and safety of Kanglaite injection combined with chemotherapy and chemotherapy alone in the treatment of advanced colorectal cancer.Methods:PubMed,Cochrane library,CNKI,VIP,Wanfang database were systematically searched by inputting keywords to explore the efficacy of Kanglaite injection combined with chemotherapy in the treatment of advanced colorectal cancer.A random-effects model was selected to evaluate the treatment outcomes.The screening of literature,the extraction of data and the assessment of methodology were independently undertaken by two reviewers.Meta analysis was performed using Revman5.3 software and stata15.0 software.Results:A total of 12 RCTs were included,with 792 cases.Compared with chemotherapy alone,Metaanalysis suggested that Kanglaite injection combined with chemotherapy can improve clinical efficiency(RR=1.45,95%CI:1.21-1.74,P<0.0001)and improve patients'quality of life(RR=1.55,95%CI:1.32-1.82,P<0.00001),improve the patient's immune function(CD3+cells:SWD=1.42,95%CI:1.11-1.73;CD4+/CD8+cell ratio:SWD=0.95,95%CI:0.66-1.25;NK cell activity:SWD=3.24,95%CI:2.81-3.66,P<0.00001);Leukopenia rate(RR=0.63,95%CI:0.54-0.74,P<0.0001),incidence of gastrointestinal adverse reactions(RR=0.56,95%CI:0.48-0.66,P<0.00001),incidence of peripheral neurotoxicity(RR=0.79,95%CI:0.65-0.96,P=0.02)were lower than the chemotherapy alone group,the difference was statistically significant.In improving the hand-foot syndrome and oral mucositis after chemotherapy,there was some difference between the Kanglaite injection combined with chemotherapy group and the chemotherapy alone group,but the difference was not significant.Puber bias detection and sensitivity analysis were performed with clinically effective relative risk(RR)as indicators.The results suggested that the publication bias was not obvious.The results of this study are stable.Conclusion:Compared with chemotherapy alone group in the treatment of advanced colorectal cancer,Kanglaite injection combined with chemotherapy can improve the effective rate,quality of life,immune function of patients and reduce the incidence of leukopenia after chemotherapy,gastrointestinal adverse reactions and peripheral neurotoxicity.

Professor YANG Yu-fei’s Experience on the Integrated Chinese and Western Medicine Treatment Strategy for Advanced Colorectal Cancer

Colorectal cancer is one of the common malignant tumors in China.It poses a serious threat to the national health of China.For advanced colorectal cancer, the main goal of treatment is to prolong survival and improve quality of life.It complements other advantages, showing good therapeutic results.However, how to grasp the timing of integrated Chinese and Western Medicine for the treatment of advanced colorectal cancer and use the integrated Chinese and Western Medicine treatment methods flexibly contains profound therapeutic art.Prof.YANG Yu-fei is an authoritative expert in the field of integrated Chinese and Western medicine for colorectal cancer.She is good at accurately grasping the timing of treatment of integrated Chinese and Western Medicine, and flexibly adjusts the treatment strategy according to the specific conditions.In this paper, we shared Professor YANG Yu-fei's strategy for treating advanced colorectal cancer with emphasis on integrated Chinese and Western Medicine and attached a typical case, with a view to provide reference for the treatment of advanced colorectal cancer with integrated Chinese and Western Medicine.

CLINICOPATHOLOGICAL CHARACTERISTICS OF ADVANCED COLORECTAL CANCER 30mm OR SMALLER IN DIAMETER

Objective To investigate the clinicopathological characteristics of advanced colorectal cancer which was 30 mm or smaller in diameter. Methods Retrospective analysis documented 80 patients with small advanced colorectal cancer from May 1985 to May 2002. According to the diameter of tumors, all patients were divided into three groups: Group A (10 mm or less), Group B (11-20 mm), Group C (21-30 mm). Considering the number of patients in Group A was smaller, we combined Group A with Group B as Group D. Then various clinicopathological characteristics were compared between Group C and Group D. Results The most common site of small advanced colorectal cancer was sigmoid colon and rectum that accounted for 36.2% and 35.0% of all cases. The average diameter of total tumors was 23.3 mm. Type 2 was the most common macroscopic type (63.7%) and the moderate differentiation was seen in 77.5% of cases. Thirty-eight (47.5%) cases had lymph node metastasis. Three (3.8%) cases had liver metastasis and three (3.8%) cases had peritoneal metastasis. The frequency of lymph node metastasis was found significantly different between Group C and Group D (54.2% vs. 28.6%, P<0.05), as well as between the groups with different depth of invasion (P<0.05). Curability A resection was performed in 69 (86.2%) cases. Conclusions Tumor size and depth of invasion are related to lymph node metastasis in small advanced colorectal cancer. However, the small size of tumor may not always be a.reliable parameter for estimating the risk of lymph node metastasis. Small colorectal cancers also do not always mean the early stage. Surgeons should be aware of the features of small advanced colorectal cancers to select ideal management and perform perfect resection.

Oxaliplatin combined with 5-fluorouracil, leucovorin regimen for patients with advanced colorectal cancer

Objective： To observe the efficacy and tolerability of continuously infusing 5-fluorouracil （5-FU） / folic acid combined with oxaliplatin （L-OHP/5-FU/LV regimen） as first line treatment in advanced colorectal cancer. Methods： 23 patients of advanced colorectal cancer were treated with 5-FU 500 mg/d, civ, d 1-d5, d8-d12, leucovorin 100 mg/d, iv gtt, d1, d8, folic acid tablet 60 mg/d, po, d2-d5, d9-d12, and oxaliplatin 65 mg/（m^2·d）, iv gtt, dl, d8, repeated every 21 days （one cycle）. The effect was evaluated after two cycles. Results： Complete response in 2 cases and partial response in 10 cases were observed with an overall response rate of 47.18%. Adverse effects were mainly grade 1-2, including nausea, vomiting, diarrhea, dental ulcer, peripheral neuritis and myelosuppression. Conclusion： L-OHP/5-FU/LV regimen is an effective and better tolerated alternative treatment in advanced colorectal cancer and yields promising clinical application.

Clinical evaluation of Fufangkushen combined with oxaliplatin in the treatment of advanced colorectal cancer

Objective:To systematically evaluate the efficacy and safety of compound Kushen injection combined with oxaliplatin chemotherapy in the treatment of advanced colorectal cancer.Methods:We searched PubMed,EMbase,the Cochrane Library,CNKI,VIP and Wan Fang database,SinoMed to collect compound Kushen injection combined with chemotherapy oxaliplatin into treatment of advanced colorectal cancer in randomised controlled trials;the databases weresearched from inception to December 2020.Meta-analysis of the included studies was performed using RevMan 5.4.Results:A total of 34 randomized controlled trials involving 2664 patients with colorectal cancer were included.Results of Meta-analysis showed that compound Kushen injection combined with oxaliplatin chemotherapy regimen improved the objective response rate of tumor[RR=1.40,95%CI(1.29,1.51),P<0.00001]and disease control rate[RR=1.12,95%CI(1.08,1,16),P 0.00001]improved the quality of life[RR=1.24,95%CI(1.14,1.36),P<0.00001],and significantly reduced the incidence of leukopenia[RR=0.35,95%CI(0.23,0.52),P<0.00001]and the incidence of diarrhea[RR=0.36,95%CI(0.19,0.70),P=0.003],and improved the immune function of patients(CD3+,CD4+,CD4+/CD8+,NK cell levels).However,compared to the control group,the levels of CD8+cells were decreased in the experimental group.Conclusion:Compound Kushen injection combined with oxaliplatin chemotherapy regimen can significantly improve the clinical efficacy of advanced colorectal cancer patients,improve the quality of life of patients,reduce the occurrence of adverse reactions,and has good efficacy and safety comparison with oxaliplatin chemotherapy regimen alone.

Has the open surgical approach in colorectal cancer really become uncommon?

Colorectal cancer is the third most common cancer in the world.Surgery is man-datory to treat patients with colorectal cancer.Can colorectal cancer be treated in laparoscopy?Scientific literature has validated the oncological quality of laparo-scopic approach for the treatment of patients with colorectal cancer.Randomized non-inferiority trials with good remote control have answered positively to this long-debated question.Early as 1994,first publications demonstrated technical feasibility and compliance with oncological imperatives and,as far as short-term outcomes are concerned,there is no difference in terms of mortality and post-operative morbidity between open and minimally invasive surgical approaches,but only longer operating times at the beginning of the experience.Subsequently,from 2007 onwards,long-term results were published that demonstrated the ab-sence of a significant difference regarding overall survival,disease-free survival,quality of life,local and distant recurrence rates between open and minimally in-vasive surgery.In this editorial,we aim to summarize the clinical and technical aspects which,even today,make the use of open surgery relevant and necessary in the treatment of patients with colorectal cancer.

A multicenter randomized phase Ⅱ trail of Oxaliplatin in the patients with colorectal cancer

Objective： To evaluate the efficacy and safety of Oxaliplatin in the patients with colorectal cancer. Methods： In a multicenter randomized control study, a total of 144 patients were divided into four groups： Oxaliplatin （Haitong） ＋ 5-FU, CF （group A） 41 cases; 5-FU ＋ CF （group B） 41 cases; Oxaliplatin （Haitong） ＋ 5-FU, CF （group C） 31 cases; Oxaliplatin （positive drug） ＋ 5-FU ＋ CF （group D） 31 cases. Oxaliplatin combination regimen： L-OHP 130 mg/m2 i.v. infusion 2 h dl; CF 200 mg/m2 i.v. 2 h d1-d5; 5-FU 300 mg/m2 i.v. infusion 4 h d1-d5 （after CF）. 5-FU ＋ CF combination regimen： CF 200 mg/m^2 i.v. infusion 2 h d1-d5, 5-FU 300 mg/m^2 i.v. infusion 4h d1-d5 （after CF）, the schedule was repeated every 3 weeks. The total cycles were 3. Results： After three circles treatment, overall response rate of 4 groups was 24.4% （group A）, 2.4% （group B）, 25.8% （group C） and 19.4% （group D）, respectively. The response rate was significantly different between group A and group B （P 〈 0.01）, but no significant difference was observed between group C and group D （P 〉 0.05）. Conclusion： The Oxaliplatin （Haitong） for injection combination regimen is effective in the treatment of celorectal cancer.

Thought and Method on Establishing the Prediction Model of TCM Dominant Population with Advanced Digestive Tract Malignant Tumors based on TCM Tumor Registration Platform

Advanced digestive tract malignant tumors,represented by advanced colorectal cancer,advanced gastric cancer and advanced esophageal cancer,have insidious onsets and high mortality.Western medicine based on targeted therapy greatly can improves the benefit and efficacy for patients through population stratification,but its population is limited.Traditional Chinese medicine(TCM)has a long history in treatment of tumors,which is an important part of comprehensive treatment of tumors.Clinical observation has shown that different patients could get different efficacy from TCM treatment.Based on real world registration studies,patients with advanced colorectal cancer,advanced gastric cancer or advanced esophageal cancer who had received TCM treatment were observed and followed,and a TCM dominant population that achieved significant efficacy was screened out to carry out multivariate regression analysis,further explore key factors that affect survival in advanced digestive tract malignant tumors,and establish a prediction model of TCM dominant population.It will provide reference for the follow-up TCM treatment,and provide reference for development of individualized treatment plans,making the TCM treatment for advanced digestive tract malignant tumors more targeted,and helping to improve the benefit rate in TCM.

Characterizing the composition of intestinal microflora by 16S rRNA gene sequencing

BACKGROUND This study determined the composition and diversity of intestinal microflora in patients with colorectal adenoma(CRA),which may provide precedence for investigating the role of intestinal microflora in the pathogenesis of colorectal tumors,the composition of intestinal microflora closely related to CRA,and further validating the possibility of intestinal flora as a biomarker of CRA.AIM To study the relationship between intestinal microflora and CRA.METHODS This is a prospective control case study from October 2014 to June 2015 involving healthy volunteers and patients with advanced CRA.High-throughput sequencing and bioinformatics analysis were used to investigate the composition and diversity of intestinal microflora in 36 healthy subjects and 49 patients with advanced CRA.Endpoints measured were operational taxonomic units of intestinal flora,as well as their abundance and diversity(αandβtypes).RESULTS In this study,the age,gender,body mass index,as well as location between controls and patients had no significant differences.The mucosa-associated gut microbiota diversity and bacterial distribution in healthy controls and colorectal adenomas were similar.The operational taxonomic unit,abundance,andαandβdiversity were all reduced in patients with CRA compared to controls.At the phylum level,the composition of intestinal microflora was comparable between patients and controls,but the abundance of Proteobacteria was increased,and Firmicutes and Bacteroides were significantly decreased(P<0.05).The increase in Halomonadaceae and Shewanella algae,and reduction in Coprococcus and Bacteroides ovatus,could serve as biomarkers of CRA.High-throughput sequencing confirms the special characteristics and diversity of intestinal microflora in healthy controls and patients with CRA.CONCLUSION The diversity of intestinal microflora was decreased in patients with CRA.An increase in Halomonadaceae and Shewanella algae are markers of CRA.