Comparative effectiveness of immunotherapy and chemotherapy in patients with metastatic colorectal cancer stratified by microsatellite instability status

BACKGROUND Immunotherapy have demonstrated promising outcomes in patients with high microsatellite instability(MSI)(MSI-H)metastatic colorectal cancer.However,the comparative effectiveness of Immunotherapy and chemotherapy for patients with low MSI(MSI-L),and microsatellite stable(MSS)metastatic colorectal cancer remains unclear.AIM To investigate immunotherapy vs chemotherapy for treatment of MSI-L/MSS metastatic colorectal cancer,and to evaluate the success of immunotherapy against chemotherapy in managing MSI-H metastatic colorectal cancer during a follow-up of 50 months.METHODS We conducted a retrospective cohort study using the National Cancer Database(NCDB)to evaluate the overall survival(OS)of patients with metastatic colorectal cancer treated with immunotherapy or chemotherapy.The study population was stratified by MSI status(MSI-H,MSI-L,and MSS).Multivariable Cox proportional hazard models were used to assess the association between treatment modality and OS,adjusting for potential confounders.RESULTS A total of 21951 patients with metastatic colorectal cancer were included in the analysis,of which 2358 were MSI-H,and 19593 were MSI-L/MSS.In the MSI-H cohort,immunotherapy treatment(n=142)was associated with a significantly improved median OS compared to chemotherapy(n=860).After adjusting for potential confounders,immunotherapy treatment remained significantly associated with better OS in the MSI-H cohort[adjusted hazard ratio(aHR):0.57,95%confidence interval(95%CI):0.43-0.77,P<0.001].In the MSS cohort,no significant difference in median OS was observed between immunotherapy treatment and chemotherapy(aHR:0.94,95%CI:0.69-1.29,P=0.715).CONCLUSION In this population-based study using the NCDB,immunotherapy treatment was associated with significantly improved OS compared to chemotherapy in patients with MSI-H metastatic colorectal cancer,but not in those with MSI-L/MSS metastatic colorectal cancer.Further studies are warranted to determine the optimal therapeutic approach for patients with MSI-L/MSS metastatic colorectal cancer.

Evaluating combined bevacizumab and XELOX in advanced colorectal cancer: Serum markers carcinoembryonic antigen, carbohydrate antigen 125, carbohydrate antigen 199 analysis

BACKGROUND Colorectal cancer ranks third and second among common and fatal cancers.The treatment of metastatic colorectal cancer(mCRC)is generally based on XELOX in clinical practice,which includes capecitabine(CAP)and oxaliplatin.Serum tumor markers carcinoembryonic antigen(CEA),carbohydrate antigen(CA)125 and CA199 are prognostic factors for various tumors.AIM To investigate evaluating combined bevacizumab(BEV)and XELOX in advanced colorectal cancer:Serum markers CEA,CA125,CA199 analysis.METHODS In this retrospective study,a total of 94 elderly patients diagnosed with mCRC were recruited and subsequently categorized into two groups based on the distinct treatment modalities they received.The control group was treated with XELOX plus CAP(n=47),while the observation group was treated with XELOX plus CAP and BEV(n=47).Several indexes were assessed in both groups,including disease control rate(DCR),incidence of adverse effects,serum marker levels(CEA,CA125,and CA19)and progression-free survival(PFS).RESULTS After 9 wk of treatment,the serum levels of CEA,CA199 and CA125 in the observation group were significantly lower than those in the control group(P<0.05).Moreover,the PFS of the observation group(9.12±0.90 mo)was significantly longer than that of the control group(6.49±0.64 mo).Meanwhile,there was no statistically significant difference in the incidence of adverse reactions and DCR between the two groups during maintenance therapy(P>0.05).CONCLUSION On the basis of XELOX treatment,the combination of BEV and CAP can reduce serum tumor marker levels and prolong PFS in patients with mCRC.

Efficacy and safety of bevacizumab plus chemotherapy in Chinese patients with metastatic colorectal cancer:a randomized phase Ⅲ ARTIST trial

The efficacy and safety of bevacizumab with modified irinotecan,leucovorin bolus,and 5-fluorouracil intravenous infusion(mIFL) in the first-line treatment of metastatic colorectal cancer(mCRC) has not been well evaluated in randomized clinical trials in Chinese patients.We conducted a phrase Ⅲ trial in which patients with previously untreated mCRC were randomized 2:1 to the mIFL [irinotecan(125 mg/m2),leucovorin(20 mg/m2) bolus,and 5-fluorouracil intravenous infusion(500 mg/m2) weekly for four weeks every six weeks] plus bevacizumab(5 mg/kg every two weeks) group and the mIFL group,respectively.Co-primary objectives were progression-free survival(PFS) and 6-month PFS rate.In total,214 patients were enrolled.Our results showed that addition of bevacizumab to mIFL significantly improved median PFS(4.2 months in the mIFL group vs.8.3 months in the bevacizumab plus mIFL group,P < 0.001),6-month PFS rate(25.0% vs.62.6%,P < 0.001),median overall survival(13.4 months vs.18.7 months,P = 0.014),and response rate(17% vs.35%,P = 0.013).Grades 3 and 4 adverse events included diarrhea(21% in the mIFL group and 26% in the bevacizumab plus mIFL group) and neutropenia(19% in the mIFL group and 33% in the bevacizumab plus mIFL group).No wound-healing complications or congestive heart failure occurred.Our results suggested that bevacizumab plus mIFL is effective and well tolerated as first-line treatment for Chinese patients with mCRC.Clinical benefit and safety profiles were consistent with those observed in pivotal phase Ⅲ trials with mainly Caucasian patients.

Study protocol of the Asian XELIRI ProjecT(AXEPT):a multinational,randomized,non-inferiority,phase Ⅲ trial of second-line chemotherapy for metastatic colorectal cancer, comparing the eicacy and safety of XELIRI with or without bevacizumab versus FOLFIRI w

Background: Capecitabine and irinotecan combination therapy(XELIRI) has been examined at various dose levels to treat metastatic colorectal cancer(m CRC). Recently, in the Association of Medical Oncology of the German Cancer Society(AIO) 0604 trial, tri?weekly XELIRI plus bevacizumab, with reduced doses of irinotecan(200 mg/m^2 on day 1) and capecitabine(1600 mg/m^2 on days 1–14), repeated every 3 weeks, has shown favorable tolerability and eicacy which were comparable to those of capecitabine and oxaliplatin(XELOX) plus bevacizumab. The doses of capecit?abine and irinotecan in the AIO trial are considered optimal. In a phase I/II study, XELIRI plus bevacizumab(BIX) as second?line chemotherapy was well tolerated and had promising eicacy in Japanese patients.Methods: The Asian XELIRI Projec T(AXEPT) is an East Asian collaborative, open?labelled, randomized, phase Ⅲ clinical trial which was designed to demonstrate the non?inferiority of XELIRI with or without bevacizumab versus standard FOLFIRI(5?fluorouracil, leucovorin, and irinotecan combination) with or without bevacizumab as second?line chemo?therapy for patients with m CRC. Patients with 20 years of age or older, histologically conirmed m CRC, Eastern Coop?erative Oncology Group performance status 0–2, adequate organ function, and disease progression or intolerance of the irst?line regimen will be eligible. Patients will be randomized(1:1) to receive standard FOLFIRI with or with?out bevacizumab(5 mg/kg on day 1), repeated every 2 weeks(FOLIRI arm) or XELIRI with or without bevacizumab(7.5 mg/kg on day 1), repeated every 3 weeks(XELIRI arm). A total of 464 events were estimated as necessary to show non?inferiority with a power of 80% at a one?sided α of 0.025, requiring a target sample size of 600 patients. The 95% conidence interval(CI) upper limit of the hazard ratio was pre?speciied as less than 1.3.Conclusion: The Asian XELIRI Projec T is a multinational phase III trial being conducted to provide evidence for XELIRI with or without bevacizumab as a second?line treatment option of mCRC.

Efficacy and safety of chemotherapy combined with bevacizumab in Chinese patients with metastatic colorectal cancer:A prospective,multicenter,observational,non-interventional phaseⅣtrial

Objective:Bevacizumab has an important and evolving role in improving outcomes in patients with metastatic colorectal cancer(mCRC)worldwide and was approved in China in 2010.However,there are limited real-world data on the efficacy and safety of chemotherapy regimens combined with bevacizumab in Chinese patients with mCRC.This observational,phase IV trial study aimed to obtain more experience on the efficacy and safety of bevacizumab combined with chemotherapy in Chinese mCRC patients.Methods:Between September 2013 and November 2016,patients with histologically confirmed mCRC were enrolled in a prospective,multicenter,observational,non-interventional phase IV trial at 26 centers across China.Eligible patients received different chemotherapeutic regimens combined with bevacizumab.The efficacy and safety data in the intention-to-treat study population were analyzed.Results:A total of 611 patients were included in the efficacy analysis.The median overall survival and median progression-free survival was 18.00 and 10.05 months,respectively.The objective response rate was 21.00%and disease control rate was 89.40%.In subgroup analyses,the survival differences were observed according to metastatic status,duration of treatment and elevation in blood pressure.A total of 613 patients were evaluable for safety assessments.And 569(92.82%)patients reported at least one adverse event(AE),and 151(24.63%)experienced grade 3 or higher AEs.The incidence of bevacizumab-associated AEs of special interest was reported in 31(5.06%)patients with hypertension(n=12),abscesses and fistulae(n=7),bleeding(n=6),proteinuria(n=3),gastrointestinal perforation(n=2)and venous thrombotic events(n=1).Conclusions:This observational phase IV trial broadens our experience and knowledge of bevacizumab in the Chinese population and provides a good indication of its overall efficacy and safety.Bevacizumab in combination with chemotherapy offers clinical benefits to Chinese patients with mCRC and has an acceptable and manageable safety profile.

Outcomes of palliative local treatment in metastatic colorectal cancer patients receiving chemotherapy plus bevacizumab

Objective The aim of this study was to assess the value of palliative local treatment of incurable metastatic lesions in colorectal cancer(CRC) patients receiving chemotherapy plus bevacizumab.Methods Data of 105 patients with histologically confirmed synchronous or metachronous metastatic CRC who received bevacizumab treatment from January 1, 2011 to January 31, 2017 were retrospectively reviewed. Sixteen(15%) patients who were treated with bevacizumab for less than 4 cycles were excluded, and finally, 89(85%) patients were enrolled. Among them, 33(37%) patients who received palliative local treatment were categorized into the palliative local treatment group, and the remaining 56(63%) patients were categorized into the chemotherapy plus bevacizumab group. The primary endpoint was overall survival(OS), which was calculated using Kaplan-Meier survival analyses. Factors possibly influencing survival were evaluated by univariate and multivariate analyses. Adverse events(AEs) were graded according to Common Terminology Criteria for Adverse Events, version 4.0. Grades 1–2 and 3–4 AEs of the two groups were compared and analyzed using the Fisher's exact test and χ~2 analysis.Results The median follow-up period was 20.4 months, ranging from 1 to 60 months. The median OS in the palliative local treatment group was 36.3 months(95% CI, 33.5–39.2), and that in the chemotherapy plus bevacizumab group was 20.5 months(95% CI, 17.6–23.4). Both the univariate(HR 0.13, 95% CI, 0.05–0.30, P < 0.001) and multivariate(HR 0.16, 95% CI, 0.07–0.39, P < 0.001) analyses showed that the addition of palliative local treatment could prolong survival compared with chemotherapy plus bevacizumab alone. There were no significant differences in the rates of common chemotherapy-or bevacizumab-related AEs between the two groups.Conclusion These findings suggest palliative local treatment is an effective and safe method for treating patients with incurable metastatic CRC receiving chemotherapy plus bevacizumab.

Systemic treatment for metastatic colorectal cancer

Significant progress has been achieved in the treatment of metastatic colorectal cancer(mCRC)patients during the last 20 years.There are currently numerous treatments available for the first-line treatment of mCRC.Sophisticated molecular technologies have been developed to reveal novel prognostic and predictive biomarkers for CRC.The development of next-generation sequencing and wholeexome sequencing,which are strong new tools for the discovery of predictive molecular biomarkers to facilitate the delivery of customized treatment,has resulted in tremendous breakthroughs in DNA sequencing technology in recent years.The appropriate adjuvant treatments for mCRC patients are determined by the tumor stage,presence of high-risk pathologic characteristics,microsatellite instability status,patient age,and performance status.Chemotherapy,targeted therapy,and immunotherapy are the main systemic treatments for patients with mCRC.Despite the fact that these novel treatment choices have increased overall survival for mCRC,survival remains optimal for individuals with non-metastatic disease.The molecular technologies currently being used to support our ability to practice personalized medicine;the practical aspects of applying molecular biomarkers to regular clinical practice;and the evolution of chemotherapy,targeted therapy,and immunotherapy strategies for the treatment of mCRC in the front-line setting are all reviewed here.

Mitomycin C and capecitabine: An additional option as an advanced line therapy in patients with metastatic colorectal cancer

BACKGROUND In recent years survival of patients with metastatic colorectal cancer(mCRC),though still limited,has improved significantly;clearly,when the disease becomes refractory to standard regimens,additional treatment options are needed.Studies have shown that mitomycin C(MMC),an antitumor antibiotic,and capecitabine,a precursor of 5-fluorouracil,may act synergistically in combination.The efficacy of MMC/capecitabine has been demonstrated in the first-line setting,but only a few small studies have tested it in the advanced-line setting,with contradictory results.received a median of 2 MMC/capecitabine cycles(range 0.5-9.0).Thirty-four patients(28.6%)experienced grade≥3 toxicity,including 2(1.7%)with grade 4;there was no drug-related mortality.The objective response rate was 0.8%,and the disease control rate,24.4%.Median progression-free survival(PFS)was 2.1 mo(range 0.2-20.3),and median overall survival,4.8 mo(range 0.2-27.5).The 6-month overall survival rate was 44%;8.7%of patients remained progression-free.Factors associated with longer PFS were lower gamma-glutamyl transferase level(P=0.030)and primary tumor location in the left colon(P=0.017).Factors associated with longer overall survival were lower gamma-glutamyl transferase level(P=0.022),left-colon tumor location(P=0.044),low-to-moderate histological grade(P=0.012),Eastern Cooperative Oncology Group performance status 0-1(P=0.036),and normal bilirubin level(P=0.047).CONCLUSION MMC/capecitabine is an active,available,and relatively safe regimen for use beyond standard lines of therapy in mCRC.Several clinical and laboratory parameters can identify patients more likely to benefit.

Total and not bevacizumab-bound vascular endothelial growth factor as potential predictive factors to bevacizumab-based chemotherapy in colorectal cancer

AIM: To identify suitable biomarkers of response to bevacizumab(BV)- it remains an open question. The measurement of serum vascular endothelial growth factor(VEGF) has been proposed as a predictive factor for this drug, even if literature data are contradictory. METHODS: We prospectively evaluated the role of BV, total and not BV-bound VEGF and angiopoietin-2(Ang-2) serum levels as potential predictive factors of response for BV in combination with an oxaliplatinbased chemotherapy. BV, Ang-2, total and not BVbound VEGF levels were measured at baseline, before 2^(nd) and 5^(th) cycle of oxaliplatin-based chemotherapy in 20 consecutive metastatic colorectal cancer patients. RESULTS: Results were correlated to response to treatment. Variability in BV levels have been found, with decreased level in less responding patients. In particular, the concentration of BV increased of 3.96 ± 0.69 folds in serum of responsive patients after 3 more cycles of therapy compared to those with stable or progressive disease with a 0.72 ± 0.25 and 2.10 ± 0.13 fold increase, respectively. The determination of free and total VEGF demonstrated that the ratio between the two values, evaluated immediately before the 2^(nd) and the 5^(th) cycle of therapy, decreased from 26.65% ± 1.33% to 15.50% ± 3.47% in responsive patients and from 53.41% ± 4.75 to 34.95% ± 2.88% in those with stable disease. Conversely, in those with progression of disease, the ratio showed the opposite behavior coming up from 25.99% ± 5.23% to 51.71% ± 5.28%. The Ang-2 levels did not show any relationship. CONCLUSION: Our data show that the ratio of not BV-bound VEGF to total VEGF serum and BV plasma concentrations for predicting the response to BV plus oxaliplatin-based chemotherapy could be a promising biomarker of response to BV.

Response evaluation of chemotherapy in metastatic colorectal cancer by contrast enhanced ultrasound

AIM:To evaluate whether contrast enhanced ultrasound(CEUS) might also be used for response prediction and early response evaluation in patients receiving bevacizumab based chemotherapy for metastasized colorectal cancer.METHODS:Thirty consecutive patients with non primary resectable liver metastases from colorectal cancer underwent CEUS before treatment(CEUS date 1) and before the second(CEUS date 2) and fourth(CEUS date 3) cycle of bevacizumab based chemotherapy.Three parameters [PEAK,Time to peak(TTP) and RISE RATE]were correlated with radiological response.RESULTS:For neoadjuvant purpose a reduction of tumour mass was required to assume clinical response.Based on these response criteria there was a significant(P < 0.001) correlation in TTP between metastases of responders(9.08 s) and non-responders(14.76 s) archived on CEUS date 1.By calculating a standardized quotient(metastases divided by normal liver tissue) we were able to define a cut off,predicting response with a sensitivity of 92.3 % and a specificity of 100 %.To reflect a palliative intention only those patients with progressive disease were classified as non-responders.In this stetting TTP was also significantly(P < 0.01) different between responders and non-responders.In contrast,Peak and Rise rate did not show any significant difference between responder and non-responder.CONCLUSION:CEUS might serve as a surrogate marker to predict treatment response in patients with metastasized colorectal cancer who receive antiangiogenic therapy.

Existing anti-angiogenic therapeutic strategies for patients with metastatic colorectal cancer progressing following first-line bevacizumab-based therapy

Continuous inhibition of angiogenesis beyond progression is an emerging treatment concept in the management of metastatic colorectal cancer patients with prior bevacizumab exposure. Treatment options include the continuation or reintroduction of bevacizumab during the second-line chemotherapy or switching to a different antiangiogenic monoclonal antibody such as aflibercept or ramucirumab. In the selection of treatment, patient-based factors such as performance status, age, tumor burden, and tolerance and sensitivity to the firstline bevacizumab-based therapy, as well as treatment-related factors such as toxicity, efficacy, and cost, should be taken into consideration.

Treatment dilemmas of cetuximab combined with chemotherapy for metastatic colorectal cancer

Although monoclonal antibodies(m Abs) against epidermal growth factor receptor(EGFR) have largely enriched the available therapeutic choices for colorectal cancer(CRC), the understanding and management of their associated clinical toxicities are limited. In addition, the combined strategies of administering EGFR m Abs and traditional cytotoxic agents, such as 5-fluorouracil, oxaliplatin and irinotecan, have resulted in a more complicated management of CRC treatment-related side effects compared with EGFR m Ab monotherapy. We believe that a thorough recognition of the toxicities of EGFR m Ab drugs is essential for physicians to increase the therapeutic index in the treatment of CRC. This review aims to summarize the existing information regarding the treatment dilemmas of cetuximab combined with chemotherapy in the management of metastatic CRC.

Bevacizumab maintenance in metastatic colorectal cancer: How long?

The management of patients with non-progressive metastatic colorectal cancer after six months of treatment has not yet been codified. The most relevant concerns are the effectiveness of maintenance versus discontinuation, and the tolerability of prolonged treatment. Here we report the case of a 72-year-old man affected by colorectal cancer with lung metastases who achieved a complete response after receiving capecitabine, oxaliplatin and bevacizumab for six months, and bevacizumab alone for six months. Bevacizumab was continued as maintenance regimen for more than three years. It was discontinued because of an arthroplasty. Fifty-eight months after beginning first-line treatment, the patientremains free from relapse. Adverse effects were minimal and easily controlled.

Neoadjuvant chemotherapy for metastatic colorectal cancer to the liver: from chemotherapy to targeting therapy

Despite the advances in surgical techniques, adjuvant chemotherapy and targeted therapy, approximately 40%-70% of patients with progressive colorectal cancer will develop liver metastases, of whom one-third are found at the time of diagnosis.[1] Surgical resection is now the standard treatment and also the only potentially curative treatment for resectable lesions.

Re-treatment Using Cetuximab and Chemotherapy in Patients with Metastatic Colorectal Cancer Harboring Wild-type RAS Gene

Colorectal cancer is a heterogeneous disease.Activating mutations in genes like K-RAS,BRAF,and PI3K contribute towards a poor prognosis of the disease.In this report,we present the case of re-treatment of a 58-year old patient of metastatic colorectal cancer with a combination of anti-EGFR and chemotherapy.The patient who harbored wild-type RAS gene was administered several lines of therapies including anti-EGFR antibodies.In spite of the different regimens involved,a significant progression of disease involving metastasis to the lungs and the brain was observed.On re-treatment with cetuximab and chemotherapy,the quality of life improved and the tumor biomarkers decreased.Re-treatment with anti-EGFR antibodies and chemotherapeutic agents can be an option for patients showing adverse prognosis after several lines of therapies.

Clinical observation of rh-endostatin combined with chemotherapy as first line treatment for metastatic colorectal cancer

Objective To analyze the efficacy and safety of Rh-endostatin combined with chemotherapy in the treatment of metastatic colorectal cancer.Methods All 60 metastatic colorectal cancer patients were divided into the test group(n = 30) and the control group(n = 30). The control group was treated with chemotherapy regime FOLFOX4(Oxaliplatin + Fluorouracil + Calcium Levofolinate), the test group was treated by Endostar combined with FOLFOX4 scheme.Results The response rates were 53.3% in test group and 36.7% in control group respectively(P < 0.05), the disease control rate were 83.3% and 73.3%(P < 0.05). The median progression-free survival in test group and control group were 7.3 months versus 5.3 months(P < 0.05) and median overall survival were 11.6 months versus 9.3 months(P < 0.05). Among 27 cases of liver metastases were sub group analysis, difference on the test group and the control group response rate(RR) and disease control rate(DCR) had statistical significance(P < 0.05), but difference on progression free survival(PFS) and overall survival(OS) had no statistical significance(P > 0.05). The major toxicities were myelosuppression, gastrointestinal symptoms, neurotoxicity, most in grade I-II. After chemotherapy, quality of life(QOL) of patients were more improved than before treatment. After treatment the carcino embryonie antigen(CEA) and caner antigent 199(CA199) levels decreased obviously, furthermore, the test group decreased more obviously than the control group. Conclusion Rh-endostatin combined with chemotherapy in the treatment of metastatic colorectal cancer is safer and effective, and also improves PFS.

Role of targeted therapy in metastatic colorectal cancer

Colorectal cancer(CRC) is a significant cause of cancer-related morbidity and mortality all over the world.Improvements of cytotoxic and biologic agents have prolonged the survival in metastatic CRC(mC RC),with a median overall survival of approximately 2 years and more in the past two decades.The biologic agents that have proven clinical benefits in m CRC mainly target vascular endothelial growth factor(VEGF) and epidermal growth factor receptor(EGFR).In particular,bevacizumab targeting VEGF and cetuximab and panitumumab targeting EGFR have demonstrated sig-nificant survival benefits in combination with cytotoxic chemotherapy in the first-line,second-line,or salvage setting.Aflibercept,ramucirumab,and regorafenib are also used in second-line or salvage therapy.Recent retrospective analyses have shown that KRAS or NRAS mutations were negative predictive markers for anti-EGFR therapy.Based on the evidence from large rand-omized clinical trials,personalized therapy is necessary for patients with m CRC according to their tumor biology and characteristics.The aim of this paper was to summarize the results of the major randomized clinical trials and highlight the benefits of the molecular targeted agents in patients with mC RC.

Standard chemotherapy with cetuximab for treatment of colorectal cancer

AIM: To review and assess the evidence related to cetuximab treatment in metastatic colorectal cancer(mCRC) with regard to KRAS status.METHODS: PubMed, EMBASE, Cochrane database and American Society of Clinical Oncology meeting abstracts were searched for randomized controlled trials(RCTs) reporting the effect of KRAS status on efficacy of chemotherapy regimen with or without cetuximab in mCRC. Baseline information such as sex and age was summarized from the included studies.Hazard ratios of progression-free survival(PFS) and overall survival(OS) as well as objective response based on KRAS status were extracted for analysis.RESULTS: A total of 8 RCTs with 6780 patients were included. The combined analysis showed that cetuximab failed to improve the OS and PFS in patients with mCRC.However, in subgroup analysis, the pooled data showed that addition of cetuximab to irinotecan containing chemotherapy regimen was sufficient to improve OS and PFS in wild-type KRAS mCRC patients, but not in patients with mutant-type KRAS. The addition of cetuximab increased the incidence of adverse events such as diarrhea, rash, skin toxicity/rash, and nausea and vomiting. There was no significant publication bias existing in the included studies.CONCLUSION: The clinical benefit of cetuximab was only confirmed in patients with wild-type KRAS. KRAS status could be considered a biomarker of efficacy of cetuximab.

Anti-angiogenic therapies for metastatic colorectal cancer:Current and future perspectives

Colorectal cancer(CRC)is the fourth most commonly diagnosed cancer and the second leading cause of cancer death in both men and women in the United States,with about 142820 new cases and 50830 deaths expected in 2013.Metastatic disease(mCRC)remains a challenge for oncologists worldwide due to its potential comorbidities.Recently,chemotherapy regimens containing 5-fluorouracil,leucovorin,oxaliplatin and irinotecan combinations are a standard of care in the metastatic disease.Currently,biological therapies involving vascular endothelial growth factor and epidermal growth factor receptor pathways,such as bevacizumab and cetuximab,have emerged as good option for improving mCRC patient survival.Now,aflibercept plus standard chemotherapy has also been approved in second line regimen for mCRC patients.Our review will discuss novel biological drugs and their indications for mCRC patients and will bring future perspectives in this regard.

Primary site resection is superior for incurable metastatic colorectal cancer

AIM:To investigate survival in patients treated with FOLFOX followed by primary site resection or palliative surgery for incurable metastatic colorectal cancer. METHODS:Between 2001 and 2009,a total of 98 patients with colorectal adenocarcinoma and non-resectable metastases were diagnosed and treated with the new systemic agent chemotherapy regimen FOLFOX. Primary site resection was carried out in 38 patients, creation of a colostomy or bypass without resection was carried out in 36 patients,and 23 were not operated on because of advanced disease.The survival times of patients in different groups were analyzed. RESULTS:There were no differences between the patients regarding their general condition,concurrent disease,or tumor stage according to AJCC classification.The median survivals of the three groups were 30.6,20.8,and 12.7 mo(log-rank P value<0.05),respectively.The postoperative complication rate was higher in the primary site resection group than in the palliative surgery group. CONCLUSION:The results indicate that there are benefits from primary site resection for incurable metastatic colorectal cancer with systemic chemotherapy.