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OBJECTIVE To systematically evaluate the efficacy and safety of immune checkpoint inhibitors （ICIs） in the treatment of metastatic colorectal cancer （mCRC）， so as to provide evidence-based reference for clinical practice. METHODS PubMed， the Cochrane Library， Web of Science， Embase， CNKI， Wanfang and VIP databases were searched to collect randomized controlled trials （RCT） of ICIs （trial group） versus traditional chemotherapy or optimal supportive treatment （control group） in the treatment of mCRC from the establishment of the database to June 1， 2022. After literature screening and data extraction， Cochrane Systematic Review Manual 5.1.0 was used to evaluate the quality of the included literature， and RevMan 5.4 software was used for meta-analysis and sensitivity analysis. RESULTS A total of 4 RCTs were included， involving 833 patients. Meta-analysis showed that the overall survival （OS） [HR＝0.77， 95%CI （0.64， 0.94）， P＝0.01] and progression-free survival （PFS） [HR＝0.67， 95%CI （0.57， 0.79）， P＜0.000 01] were significantly higher in trial group than control group； the difference was not statistically significant when comparing the incidence of grade 3 and above adverse events in the two groups [RR＝1.22， 95%CI （0.77， 1.94）， P＝0.39]. Subgroup analysis by mutation pattern showed that patients with mismatch repair proficiency and low levels of microsatellite instability （pMMR-MSS） mCRC patients in trial group had significantly higher PFS than control group （P＜0.05）. The results of sensitivity analysis showed that the results were robust. CONCLUSIONS Compared with traditional chemotherapy or optimal supportive treatment， ICIs can prolong the OS and PFS of mCRC patients， and maybe has more advantages in pMMR-MSS mCRC patients； the safety of ICIs is equivalent to that of traditional chemotherapy or optimal supportive treatment.
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Colorectal cancer is one of the most common malignant tumors of digestive tract. In 2020， 1.93 million new cases of colorectal cancer were diagnosed globally， ranking third in the global incidence spectrum， and 930 000 new deaths were reported， ranking second in the global cause of death spectrum. Meanwhile， the medical cost of metastatic colorectal cancer is the highest among all stages. A large number of studies have demonstrated that traditional Chinese medicine（TCM） treatment can bring clinical benefits to patients with metastatic colorectal cancer with unique efficacy. In order to further standardize the TCM diagnosis and treatment for metastatic colorectal cancer and improve the level of TCM diagnosis and treatment， Xiyuan Hospital， China Academy of Chinese Medical Sciences， together with other relevant units in China， according to the guideline development process of the World Health Organization Handbook for Guideline Development and the relevant requirements of the Clinical Evidence Grading Criteria on TCM Based on Evidence Body， the Regulations for Group Standards of China Association of Chinese Medicine and others， combined with the characteristics of TCM diagnosis and treatment and the actual situation in China， the Guidelines for TCM Diagnosis and Treatment of Metastatic Colorectal Cancer was developed in accordance with the Catalogue of TCM Diagnosis and Treatment Plans for 105 Diseases in 24 Specialties issued by Department of Medical Administration of National Administration of TCM.
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Objetivo: Avaliar a custo-efetividade da trifluridina/cloridrato de tipiracila (FTD/TPI) em comparação ao melhor cuidado de suporte (sigla em inglês BSC, best supportive care) e ao regorafenibe para o tratamento em pacientes com câncer colorretal metastático (CCRm) politratados (terceira linha ou linhas posteriores) sob a perspectiva de pagadores privados no Brasil. Métodos: Foi construído um modelo de sobrevida particionado considerando três estados de saúde. A efetividade foi medida em anos-vida ganhos e Quality-Adjusted Life Years (QALY). Os custos foram obtidos a partir da perspectiva do sistema de saúde privado brasileiro considerando um horizonte temporal de cinco anos. Também foram realizadas análises de sensibilidade univariada e probabilística para avaliar a robustez do modelo. Resultados: A utilização de FTD/TPI pode gerar melhores desfechos clínicos versus BSC e economia de recursos versus regorafenibe. FTD/TPI proporcionou mais 0,098 anos de vida por paciente e uma qualidade de vida incremental de 0,072, comparada ao BSC. Já em relação ao regorafenibe, a FTD/TPI apresentou redução de R$ 2.088,49 nos custos por paciente e benefícios clínicos com incremento marginal. Conclusão: FTD/TPI representa uma opção de tratamento de CCRm custo-efetiva, comparada ao regorafenibe, na perspectiva de pagadores privados no Brasil
Objective: To determine the cost-effectiveness analysis of trifluridine/tipiracil chloridrate (FTD/TPI) compared to best supportative care (BSC) and regorafenib for the treatment of polytreated metastatic colorectal carcinoma (mCRC) (3rd line or later lines) in the private payer perspective in Brazil. Methods: A partitioned survival model was developed based on three health states. Effectiveness was measured in life-years gained and Quality-Adjusted Life Years (QALYs). Costs were obtained from the perspective of the supplementary healthcare system in Brazil considering a time horizon of five years. Univariate and probabilistic sensitivity analyses were performed to evaluate the robustness of the model. Results: The use of FTD/TPI may generate better clinical outcomes versus BSC and resource savings versus regorafenib. FTD/TPI provided more 0,098 years of life per patient and an incremental quality of life of 0,072 compared to BSC. Regarding regorafenib, FTD/TPI provided a cost reduction of R$ 2.088,49 per patient and similar clinical benefits. Conclusion: FTD/TPI represents a cost-effective treatment option for mCRC compared to regorafenib from the perspective of the supplementary healthcare system in Brazil
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Colorectal Neoplasms , Trifluridine , Economics, Pharmaceutical , Cost-Effectiveness AnalysisABSTRACT
Colorectal cancer is one of the common malignant tumors,and its morbidity and mortality are in the third and fourth places,respectively. About 60% of patients are in an advanced stage at the diagnosis,and their 5-year survival rate is around 13% . In the past 20 years,since the standardized application of advanced first-line chemotherapy and targeted drugs for metastatic colorectal cancer(mCRC),mCRC treatment has made a major breakthrough. The use of oxaliplatin,capecitabine,bevacizumab,cetux-imab and other drugs have doubled the median survival and increased the 5-year survival rate by 20% . The usual mode of first-line treatment of mCRC in the late stage is continuous medication until the disease progress or the intolerable toxicity occurs. However,be-cause of the accumulation of toxicity of chemotherapy drugs,only one-third of patients can continue to receive treatment until the dis-ease progresses. After completing established initial treatment cycle and achieving CR/PR/SD,the patients continue to use low -dose,low-toxic drugs for maintenance treatment,which can delay the progression and metastasis of the tumor,and reduce the side effects of drug. At present,maintenance therapy has become the main treatment mode after advanced first -line chemotherapy for mCRC. However,the optimal maintenance regimen for mCRC remains inconclusive,and existing maintenance regimens still do not find a balance between optimal outcome and maximum quality of life. This article will review the clinical studies of mCRC′s existing main-tenance treatment regimens,summarize the current status of mCRC maintenance therapy,and discuss individualized treatment strate-gies.
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Objective V-raf murine sarcoma virus oncogene homologous gene B (BRAF) gene plays an important role in mitogen-activated protein kinase signaling pathway by encoding RAF family serine/ threonine protein kinase.Mutations in the BRAF gene can lead to tumorigenesis.About 10％ of metastatic colorectal cancers have BRAF gene mutations.The prognosis of this type of cancer is poor,with a median overall survival of 12 months.Recent studies have shown that FOLFOXIRI regimen combined with bevacizumab can be used as a first-line treatment.In addition,simultaneous targeting inhibition of multiple signaling pathways can bring survival benefits to these patients.
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Patients with unresectable metastatic colorectal cancer live for a median of three years when treated with standard therapies. While the evidence guiding cancer-directed treatment of this disease comes from phase III trials that have mostly enrolled patients with good performance status, some patients present with poor clinical conditions. The best treatment for these patients remains to be determined. We performed a systematic review of the treatment outcomes of patients with metastatic colorectal cancer and poor performance status, defined as Eastern Cooperative Oncology Group performance status ≥2. Eligible articles were prospective or retrospective studies or case reports published in English, Portuguese or Spanish. We searched PubMed, EMBASE, LILACS and the Cochrane Library from onset until October 2017 using specific keywords for each search. We found a total of 18 publications, mostly case reports and retrospective studies (14 articles). One was an uncontrolled prospective trial, two were observational studies and one was an individual patient meta-analysis. Although some studies suggested benefits in terms of symptomatic response with standard chemotherapy, with good safety profiles when dose-reduced regimens were administered, a true survival gain could not be demonstrated. The scientific evidence for treating metastatic colorectal cancer patients with poor performance status is scarce, and more studies evaluating treatment for this population are necessary since this condition is not uncommon in clinical practice, particularly in the public healthcare system and developing countries and among destitute populations.
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Humans , Severity of Illness Index , Colorectal Neoplasms/therapy , Evidence-Based Medicine , Antineoplastic Protocols , Neoplasm Metastasis , Prognosis , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Survival AnalysisABSTRACT
OBJECTIVE:To evaluate the cost-effectiveness of SOX regimen(tegafur+oxaliplatin)vs. CapeOX regimen (capecitabine+oxaliplatin)in the treatment of metastatic colorectal cancer,and to provide reference for exploring more economical first-line regimen of metastatic colorectal cancer. METHODS:Based on published high-quality Ⅲ-phase randomized controlled trial,Markov model was established according to the process of disease development in patients with metastatic colorectal cancer. The model was divided into progression-free survival state,progressive disease state and death state. Combined with relevant data of our hospital,pharmacoeconomic cost-effectiveness analysis was conducted for SOX regimen and CapeOX regimen. Sensitivity analysis validation model was used to analyze the stability of the model. RESULTS:According to the results of Markov model operation,compared to standard CapeOX regimen,SOX regimen could increase 0.14 QALYs,and cost increased by 35 493.45 yuan;incremental cost-effectiveness ratio was 253 524.64 yuan/QALYs,which was higher than willingness-to-pay(WTP) threshold(168 201.201 yuan/QALYs). Single factor sensitivity analysis showed that cost of oxaliplatin had the most important impact on the result of cost-effectiveness analysis. Probabilistic sensitivity analysis depicted that with the increase of GDP per capita,the probability of SOX regimen with cost-effectiveness would increase. CONCLUSIONS:At present,compared with standard CapeOX regimen,SOX regimen has no cost-effectiveness for metastatic colorectal cancer,which is not recommended as the first choice for first-line treatment of metastatic colorectal cancer.
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<p><b>OBJECTIVE</b>To verify the efficacy and safety of Quxie Capsule () in patients with metastatic colorectal cancer (mCRC).</p><p><b>METHODS</b>The present study was a randomized, double-blind, placebo-controlled trial. Sixty patients with mCRC were randomized into two groups at a 1:1 ratio by sealed envelope. The treatment group received conventional therapy combined with Quxie Capsule for 3 months. The control group was treated with conventional therapy combined with placebo for 3 months. Main outcome measures were overall survival (OS) and progression-free survival (PFS). Subgroup analysis was performed according to age, right or left-sided disease, and second-line therapy to determine the differences in PFS and OS between the two groups. Patients were followed up every 3 months until Dec 31st 2016.</p><p><b>RESULTS</b>The median OS was 23 months in the treatment group [95% confidence interval (CI): 15-not calculated] vs. 14 months in the control group (95% CI: 11-22, P=0.060). The OS of the treatment group tended to be longer than that of the control group (P>0.05). In the subgroups of patients <65 years old, left-sided colon, and 2nd-line therapy, the treatment group showed a significant survival benefit compared with the control group (P=0.006, 0.038, 0.013, respectively). There were no significant differences between the two groups in PFS (P>0.05). Safety analysis showed no severe hematological toxicity or liver and renal function injury in the treatment group.</p><p><b>CONCLUSIONS</b>Quxie Capsule showed good safety and efficacy, and could prolong the OS of patients with mCRC. (Registration No. ChiCTR-IOR-16009733).</p>
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Capsules , Colorectal Neoplasms , Drug Therapy , Pathology , Disease-Free Survival , Double-Blind Method , Drugs, Chinese Herbal , Therapeutic Uses , Neoplasm Metastasis , PlacebosABSTRACT
To compare the efficacy and safety of cetuximab biweekly regimen with those of standard weekly regimen as a first-line therapy of KRAS/RAS wild-type metastatic colorectal cancer. Methods: Patients who received weekly or biweekly administra-tion of cetuximab plus FOLFOX/XELOX as a first-line therapy from July 2010 to December 2017 in Cancer Hospital, Chinese Academy of Medical Sciences were retrospectively screened for eligibility. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and frequencies of adverse events (AEs) between the two groups were compared. Results: Of 152 eligible patients, 55 were in the biweekly group and 43 were in the weekly group. The biweekly group had significantly higher ORR than the weekly group (76.3% vs. 54.8%, P=0.025). Median PFS in the biweekly and weekly groups were 10.3 and 8.8 months, respectively (P=0.288), and the median OS were 33.5 and 27.4 months, respectively (P=0.563). The two groups showed no significant difference in PFS and OS. For overall AEs, the biweekly group presented significantly more stomatitis (32.7% vs. 14.0% , P=0.032) and tended to show substantially more acne-like rash (80.0% vs. 62.8%, P=0.058) and leukopenia and/or neutropenia (72.7% vs. 55.8%, P=0.081). The frequency of 3/4 grade acne-like rash in the biweekly and weekly groups were 18.2% and 7.0%, respectively (P=0.105). The frequency of all grade 3/4 AEs between the two groups showed no significant difference (P>0.05). Conclusions: Biweekly regimen of cetuximab plus FOLFOX/XE-LOX had similar efficacy and higher ORR compared with those of standard weekly regimen. Cetuximab administered biweekly may be an optional choice in clinical practice, with close attention paid to increased frequency of certain AEs.
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<p><b>OBJECTIVE</b>To investigate the efficacy of integrated Chinese and Western medicine (IM) in the treatment of metastatic colorectal cancer (mCRC) in a cohort study.</p><p><b>METHODS</b>The survival outcome of patients receiving IM was compared with that of patients receiving Western medicine alone. The study design was adopted with "continuous administration of Chinese medicine for ⩾ 3 months" as the exposure factor. Patients who met this exposure factor were assigned to the IM cohort (Group A, 110 patients). Patients who did not meet this exposure factor were assigned to the Western medicine cohort (Group B, 225 patients). The overall survival (OS), progression-free survival (PFS), and 1st year, 2nd year, and 3rd year survival in the two cohorts were compared.</p><p><b>RESULTS</b>The median OS in Group A and B were 18 months [95% confidence interval (CI) 15-21] and 16 months (95% CI 14-18), respectively, and the median PFS in Group A and B were 6 months (95% CI 4-7) and 5 months (95% CI 4-6), respectively. No statistically significant differences were observed between the groups (P=0.186, P=0.223). Group A demonstrated significantly longer OS and PFS than Group B in the following subgroups: female patients, patients with lesions in the right half of the colon, and those who received first-line treatment (P<0.05). In the subgroup of elderly patients (age>65 years), the OS in Group A was longer than that in Group B (P<0.05).</p><p><b>CONCLUSION</b>IM could prolong the survival of patients with mCRC. (Registry No. ChiCTR-IOR-17010497).</p>
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ABSTRACT Background: Colon cancer (CC) one of the most common oncological disease in World. Up to 30% patients in Russia have metastatic CC at first visiting to oncologist. The treatment results still controversial. Nowadays, minimally invasive laparoscopic precision technique allowed extending the indication for cytoreductive surgery even in patients with severe comorbidities. Materials and methods: 89 patients with colon cancer (T1-4a) and curable synchronous distant metastases include in study. All patients underwent cytoreductive surgery with primary tumor resection. In study group (44) we performed laparoscopic surgery, in main group (45) - open surgery procedure. The groups were similar by sex, age, tumor localization and histological structure, comorbidities. Results: R0 resection performed 27% patients. The average number of lymph node removal was similar 13 and 12 respectively. Average operation time was significantly longer in study group 210 vs 120 min. In study group blood loss was lower: 300 mL vs 1200 mL. Postoperative patient recovery shorter after laparoscopic surgery (p < 0.05): time to activation 2.2 vs 3.9 days; time to first peristalsis - 1.8 vs 4.5 days; first bowel movement - 3.4 vs 4.8 days; first food taken - 2.9 vs 3.9 days. Shorter time of analgesics intake - 2.3 vs 4.4 days, p < 0.05. Hospital stay shorter: 9.3 vs 13.4 days, p = 0.05. Time to start chemotherapy reduced since 27.5 to 14.7 days, p < 0.05. Postoperative complications lower in study group: 6.8 vs 17.8%, p = 0.05. Kaplan-Meier 2-year overall survival were similar: 69.5% vs 61.6%, p = 0.96. Conclusion: Laparoscopic cytoreductive surgery for metastatic CC is safe, minimized surgical trauma and speed up patient recovery.
RESUMO Fundamento: Câncer de cólon (CC) é uma das doenças oncológicas mais comuns no mundo. Até 30% dos pacientes na Rússia têm CC metastático na primeira visita ao oncologista. Os resultados do tratamento ainda são controversos. Atualmente, a técnica de precisão laparoscópica minimamente invasiva permitiu estender a indicação para a cirurgia citorredutora mesmo em pacientes com comorbidades graves. Materiais e métodos: 89 pacientes com câncer de cólon (T1-4a) e metástases distantes síncronas curáveis foram incluídos no estudo. Todos os pacientes foram submetidos à cirurgia citorredutora com ressecção do tumor primário. No grupo de estudo (44) realizamos cirurgia laparoscópica, no grupo principal (45), a cirurgia aberta. Os grupos eram semelhantes em relação à sexo, idade, localização e estrutura histológica do tumor, e comorbidades. Resultados: A ressecção R0 foi realizada em 27% dos pacientes. O número médio de remoção de linfonodos foi similar, 13 e 12, respectivamente. O tempo médio de cirurgia foi significativamente mais longo no grupo de estudo, 210 versus 120 min. A perda de sangue foi menor no grupo de estudo: 300 mL versus 1200 mL. A recuperação pós-operatória foi mais curta após a cirurgia laparoscópica (p < 0,05): tempo de ativação - 2,2 vs. 3,9 dias; tempo até o primeiro peristaltismo - 1,8 vs. 4,5 dias; primeiro movimento intestinal - 3.4 vs. 4.8 dias; primeiro alimento consumido - 2.9 vs. 3.9 dias. Menor tempo de ingestão de analgésicos - 2,3 versus 4,4 dias, p < 0,05; menor tempo de hospitalização: 9,3 vs. 13,4 dias, p = 0,05. O tempo para iniciar a quimioterapia foi reduzido de 27,5 para 14,7 dias, p < 0,05. Complicações pós-operatórias menores no grupo de estudo: 6,8 vs. 17,8%, p = 0,05. A sobrevivência global de Kaplan-Meier aos 2 anos foi semelhante: 69,5% vs. 61,6%, p = 0,96. Conclusão: A cirurgia citorredutora laparoscópica para CC metastático é segura, minimiza o trauma cirúrgico e acelera a recuperação do paciente.
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Humans , Colorectal Neoplasms/surgery , Adenocarcinoma , Cytoreduction Surgical Procedures/methodsABSTRACT
The development of anti-epidermal growth factor receptor monoclonal antibodies (anti-EGFR McAbs) marked a significant milestone in metastatic colorectal cancer (mCRC) treatment. The addition of anti-EGFR McAb can greatly improve quality of life of mCRC patients and mCRC prognosis and markedly increases the overall survival rate from 6 months to nearly 30 months. KRAS and NRAS mutations contribute to the primary resistance to anti-EGFR therapy and can serve as well-established predictive markers for pa-tient selection. Apart from the RAS family, other molecular alteration in EGFR signaling pathway may also compromise the efficacy of anti-EGFR treatment. In addition, patients who responded to anti-EGFR treatment eventually develop acquired drug resistance within 13 and 18 months. In this review, the mechanisms underlying the primary and secondary resistance to anti-EGFR therapy are summa-rized, and a possible strategy to circumvent drug resistance is proposed. We hope this review can provide compelling evidence, deeper insights, and reasonable guidance to facilitate the precise molecular targeted therapy of mCRC.
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Background and purpose: Current colorectal cancer patient-derived xenografts (PDXs) models were established by samples taken during surgery. However, metastatic colorectal cancer (mCRC) patients have less surgical opportunities, and it was difcult to obtain enough tumor fragment. The aim of the present study was to es-tablish mCRC PDXs by image-guided biopsy. Methods: A total of 12 patients with colorectal cancer who underwent surgery were included. All patients had recurrent lesions or metastatic lesions needed to be histologically confirmed, and none of them had contraindication to biopsy. Tumor tissues not required for clinical diagnosis were used to establish mCRC PDXs. Results: Seven PDXs grew sufficiently for transfer into mice. The success rate was 77.8%. Conclusion:The PDXs established by image-guided biopsy had the advantage of convenient operation, good reproducibility, high achievement ratio, short experimental periodicity and reliably retain specific genetic and morphological features of the primary patient tumors.
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Objective To investigate the effect of bevacizumab combined with chemotherapy on the expression of EGFR and HER in the patients with metastatic colorectal cancer .Methods Sixty patients with metastatic colorectal cancer treated in this hos-pital from January 2013 to October 2016 were selected and randomly divided into the experiment group (bevacizumab combined with FOLFOX-6 chemotherapy regimen) and control group (FOLFOX-6 chemotherapy regimen) 30 cases in each group .The curative effects were observed in the two groups .The levels of serum HER and EGFR were detected by enzyme-linked immunosorbent assay (ELISA) .Results The total effective rate after treatment in the experiment group was 53 .33% ,which in the control group was 33 .33% ,the difference was statistically significant (P< 0 .05) .After treatment ,the levels of serum HER and EGHR in the two groups were decreased to some extent ,moreover the experiment group had more decrease than the control group ,the difference be-tween the two groups was statistically significant (P<0 .05) .The occurrence rate of adverse reactions had no statistical difference between the two groups (P>0 .05) .Conclusion Bevacizumab combined with chemotherapy has good effect in the patients with metastatic colorectal cancer .
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Objective: To compare the treatment costs of different sequences of regimens including monoclonal antibodies in metastatic colorectal cancer (CRCm) treatment for the Brazilian Supplementary Healthcare System. Methods: Sixteen scenarios were analyzed, each one comparing a sequence of bevacizumab TML plus an anti-EGFR therapy in the third?line with another sequence without bevacizumab TML (non-Bev TML) in patients with CRCm wild-type RAS. The anti-EGFRs cetuximab and panitumumabwere included. The monthly and total costs of the therapeutic sequences were compared per patient. Results: The sequences with Bev TML were cost-saving in 50% of all scenarios, and especially observed over regimens starting with cetuximab in the first-line treatment. Regarding scenarios whichthe non-Bev TML sequences were less costly, they all started with bevacizumab followed by an anti-EGFR biologic drug. Conclusion: The Bev TML regimens were cost-saving compared to scenarios of non-Bev TML which started with cetuximab, and sequential use of bevacizumab beyond progression and the addition of an anti-EGFR biologic drug in the third-line for mCRC treatment. Considering the remaining scenarios in which Bev-TML was not cost-saving, those starting with Bev presented lower costs in total. Therefore, starting a treatment with bevacizumab seems to enable a more rational management of resource usage, as well as, to allow physicians to add a biologic drug in the third-line, potentially enhancing the long term management of wild-type RAS mCRC.
Objetivo: Comparar o custo de tratamento de diferentes sequências de regimes incluindo anticorpos monoclonais no tratamento de câncer colorretal metastático (CCRm) no Sistema de Saúde Suplementar Brasileiro. Métodos: Dezesseis cenários foram analisados, cada um comparando umasequência de bevacizumabe TML (Bev TML) mais um anti-EGFR em terceira linha, com outra sequência sem bevacizumabe TML (não-Bev TML). Os anti-EGFRs cetuximabe e panitumumabe forma incluídos. Os custos mensais e totais do sequenciamento terapêutico foram comparados por pacientes. Resultados: As sequências com Bev TML trouxeram economia de recursos em 50% de todos os cenários, e especialmente comparado aos regimes iniciando com cetuximabe em primeira linha detratamento. Considerando os cenários em que os regimes não-Bev TML apresentaram menos custo, todos iniciaram o sequenciamento com bevacizumabe seguido de um medicamento biológico anti-EGFR. Conclusões: Os regimes Bev TML apresentaram economia de recursos comparado aos cenários com não-Bev TML que iniciaram com cetuximabe, apesar do uso de bevacizumabe em múltiplas linhas e da adição de medicamento biológico anti-EGFR em terceira linha no tratamento de CCRm. Considerando os demais cenários em que os regimes Bev-TML não apresentaram economia de recursos, os regimes iniciando com Bev apresentaram menor custo total. Desta maneira, iniciar o tratamento com bevacizumabe proporciona um gerenciamento mais racional de uso de recursos, assim como, permite aos médicos adicionar um medicamento biológico em terceira linha, potencialmente melhorando o manejo a longo prazo do CCRm com RAS selvagem.
Subject(s)
Humans , Colorectal Neoplasms , Health Care Costs , Supplemental HealthABSTRACT
Objective To study bevacizumab combined with chemotherapy regimen in treatment of different metastasis survival in patients with colorectal cancer, in order to optimize the scheme selection of bevacizumab for metastatic colorectal cancer metastasis , improve survival and quality of life of patients with rectal cancer.Methods 128 cases of late January 2013~2013 year in June in general hospital of medical university for treatment of metastatic colorectal cancer patients as the research object, which were randomLy divided into A, B, C, D 4 groups, 32 cases in each group, respectively with bevacizumab (5 mg/kg) combined with FOLFIRI and bevacizumab (10 mg/kg) combined with FOLFIRI and bevacizumab (5 mg/kg) combined with FOLFOX and bevacizumab ( 10 mg/kg ) therapy combined with FOLFIRI regimen, four patients underwent 6 cycles of treatment.Comparison of four groups of patients with recent clinical efficacy, progression free survival (survival progression-free, PFS), three years survival rate, overall survival (overall survival, OS).Results Four groups of patients with gender, age, stage of disease, ECOG score before treatment, primary tumor site, tumor metastasis, metastasis tumor diameter, there were no significant differences.Toxicity of different degrees occurred in the four groups during treatment, but the patients tolerated and complete the established chemotherapy.A, B, C, D group total effective rate were 56.25%, 59.38%, 46.88%, 50%, 3 years survival rates were 25%, 18.75%, 28.13%, 18.75%, PFS respectively: (9.5 ±1.1), (9.6 ±1.1), (9.2 ±1), (9.3 ± 0.9) months, overall survival were: (30.23 ±2.26), (29.83 ±2.24), (26.94 ±2.08), (27.19 ±2.11) months.A, B group of patients in the clinical total effective rate, three years survival rate were higher than that of C and D two groups, but there were no statistically significant difference between the two groups.A, DFS and TTP in B group were significantly higher than that of C and D two groups, and there were significant differences among the groups (P all <0.05), the difference between the two groups was no statistically significant, C, D between the two groups there was no significant difference, A, B groups were significantly higher than that of C, OS in D two group, and the difference between the two groups were statistically the significance (P<0.05), A, B between the two groups, but no significant difference, C, D between the two groups there was no significant difference.Conclusion according to the 5-10 mg/kg/m2 of bevacizumab combined with FOLFIRI regimen in the treatment of metastatic colorectal cancer, can effectively improve progression free survival in patients with a high clinical value to promote the transfer of clinical overall survival of patients with colorectal cancer.
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Objective:To explore genes associated with sensitivity to anti-EGFR therapy. Methods:From March 2012 to August 2013, 31 metastatic colorectal cancer patients in Peking University Cancer Hospital&Institute were treated with anti-EGFR mono-therapy. A total of 21 genes associated with oncogenesis, metastasis, and EGFR signaling pathway were profiled in these 31 patients by using tar-geted next-generation sequencing technology. Results:A total of 31 patients with Kras exon 2 wild-type received anti-EGFR therapy as third-line treatment. Among these patients, the median progression-free survival (PFS) was 89 days, overall survival was 311 days, and objective response rate was 16.1%. Five cases harbored Kras exons 3/4 or Nras exons 2/3 mutations. These five Ras mutation patients showed disease progression during the first evaluation with 31-day PFS. One PIK3CA mutation case exhibited disease progression dur-ing the first evaluation (PFS 35 days), and one case showed mTOR mutation with 91-day PFS. The PFS of two cases with SMAD4 muta-tion were 58 and 59 days, whereas that of the case containing FBXW7 mutation was 93 days. Among the 26 Ras wild-type patients, MLL3, TP53, and APC were the three genes with the highest mutation frequencies of 92.3%(24/26), 53.8%(14/26), and 42.3%(11/26), respectively. Conclusion:Extended Ras analysis (including Kras and Nras exons 2/3/4) is recommended for patients who are candi-dates for anti-EGFR therapy. Mutations in the downstream effectors of the EGFR signaling pathway, such as PI3KCA and mTOR, may al-so have a predictive role in anti-EGFR therapy. Mutations beyond the EGFR pathway such as FBXW7 and SMAD4 may be associated with anti-EGFR efficacy and deserve further attention.
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Objective: To investigate the survival and individualized therapy of metastatic colorectal cancer (mCRC) patients who achieved a stable disease state after induction chemotherapy. Methods:Data were reviewed from 204 metastatic colorectal cancer pa-tients, who presented a stable disease state after first-line and second-line chemotherapy at Tianjin Medical University Cancer Insti-tute and Hospital. The clinical and pathological characteristics were analyzed. Moreover, we analyzed the significance of maintenance treatment in patients with certain mCRC characteristics. Results:Univariate analysis indicated that the line of chemotherapy, levels of CA724, CEA, and CA19-9, and platelet-to-lymphocyte ratio (PLR) were considered prognostic factors of treatment after induction che-motherapy. According to the multivariate analysis, first-line chemotherapy, as well as low levels of CA19-9 and PLR, with maintenance treatment after the induction chemotherapy was significantly associated with better survival. Among the patients with high levels of PLR, those who underwent maintenance treatment achieved a progression-free survival of 13.43 months (versus 10.63 months in pa-tients from the observation group, P=0.003). Conclusion:The levels of CA19-9 and PLR, and treatment after chemotherapy were signif-icant prognostic factors for mCRC patients who achieved a stable disease state after induction chemotherapy. These patients, especial-ly those with high PLR, could benefit from the maintenance treatment.
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Background: Discovery of novel biomarkers of prognosis and drug response remains an elusive, yet critical goal. Thus, accurate and rapid screening of an array of pertinent mutations/SNPs is an essential step in cancer management. Methods: Using a high-throughput multiplex PCR microarray technique, we simultaneously screened the mutational status/SNP of 32 hotspots in multiple genes for metastatic colorectal cancer (mCRC) from 126 formalin fixed paraffin embedded samples from 78 patients. The efficacy of the technology was validated by cross-comparison with conventional Sanger sequencing and pyrosequencing. The clinical outcome was corroborated to the mutational status to determine prognostic and predictive significance of the 32 loci. Results: In a statistically robust multivariate model, patients with the TT genotype of the MGMT gene (rs1625649) enjoyed a significantly longer survival (61.8 months) when compared to those with GG or heterozygous GT genotype (29.3 months) [HR 0.30; 95% CI: 0.10-0.89, P= 0.03], with a 70% reduced risk of death from mCRC. Conclusion: The rs1625649 SNP within MGMT is a novel and potentially valuable prognostic biomarker for mCRC patients.
ABSTRACT
OBJECTIVE:To investigate clinical efficacy of oxaliplatin+calcium folinate+5-fluorouracil(mFOLFOX6),oxalipl-atin+capecitabine(CapeOX),irinotecan+calcium folinate+5-fluorouracil(FOLFIRI)for metastatic colorectal cancer,and to conduct cost-effectiveness analysis. METHODS:48 patients with colorectal cancer were divided into mFOLFOX6 group(30 cases),Cape-OX group(8 cases)and FOLFIRI group(10 cases). Clinical efficacy and ADR of 3 groups were analyzed,and cost-effectiveness analysis was also conducted. RESULTS:Clinical effective rates of mFOLFOX6 group,CapeOX group and FOLFIRI group were 96.67%,87.50% and 80.00%,respectively,the mFOLFX6 group was significantly higher than the other 2 groups,with statistical significance(P0.05). The C/E of mFOLFOX6 group,CapeOX group and FOLFIRI group were 11 950,15 674 and 18 397 re-spectively,to which results of sensitivity analysis were same. CONCLUSIONS:The cost-effectiveness of mFOLFOX6 regimen is superior to CapeOX and FOLFIRI regimen in the treatment of metastatic colorectal cancer,but it has the high incidence of gastroin-testinal side effects.