Regimen For Colorectal Cancer Research Articles

Short‐duration Aerobic Exercise Improves Chemotherapy Induced Physical Dysfunction in Mice

Chemotherapy regimens for colorectal cancer cause body weight loss, fatigue, and weakness that may persist long after treatment completion. While increased physical activity can help to mitigate these effects, low adherence to standard exercise prescriptions limits the therapeutic potential. Therefore, it is necessary to determine if an exercise threshold is required to improve chemotherapy toxicity. Gaps remain in our understanding of the extent of chemotherapy toxicities after treatment completion, and if a low dose of exercise is sufficient to improve chemotherapy‐induced dysfunction.PurposeTo examine the effects of exercise dose on body composition and physical function in mice during the recovery from Folfox chemotherapy.MethodsMale C57BL/6J mice (12wks) were injected with 4 cycles (1 cycle= 1 injection every other wk) of Folfox (FOL; 5FU 30mg/kg, Oxaliplatin 6mg/kg, Leucovorin 90mg/kg) or PBS. Mice were sacrificed 0wks (n=8) or 4wks (n=16) after the 4th cycle. Subsets of mice performed 14 sessions (6d/wk, 5% grade) of short‐ (15min/d; n=10) or long‐duration (60min/d; n=10) treadmill exercise during recovery. Body composition by MRI, treadmill run time to fatigue (RTF), and grip strength tests were performed pre, post, and after 4wks recovery.ResultsFOL treatment attenuated body mass gain (PBS 10%, FOL 3%) independent of food intake (p=0.586) or cage activity (p=0.801). Fat mass accumulation was decreased (PBS: 56%, FOL: ‐3%) with no changes in lean mass during treatment. During recovery, body mass remained suppressed (‐8%; p=0.022), and RTF (‐43%; p<0.01) and grip strength were reduced (‐9%; p=0.045) in FOL mice compared to PBS. Treadmill exercise improved body weight loss (3%; p=0.041) independent of fat mass. Long‐ compared to short‐duration exercise increased lean mass (p<0.01) in both treatment groups. Both short‐ and long‐duration exercise improved RTF (93%; p<0.01) without improving grip strength.ConclusionRepeated cycles of Folfox chemotherapy can induce persistent deficits in physical function and fat mass. Two weeks of short‐duration aerobic exercise was sufficient to reverse chemotherapy induced fatigue without improving strength. Future studies should examine if the combined effects of aerobic and resistance exercise can improve strength.

Progress in pulmonary enteric adenocarcinoma

Pulmonary enteric adenocarcinoma (PEAC), as a rare histologic subtype of primary lung adenocarcinoma, is defined as an adenocarcinoma in which the enteric component exceeds 50%. It is named after its shared morphological and immunohistochemical features with colorectal cancer. While with such similarity, the differential diagnosis of PEAC and lung metastatic colorectal cancer is a great challenge in the clinic. PEAC may originate from the intestinal metaplasia of respiratory basal cells stimulated by risk factors such as smoking. Current studies have found that KRAS is a relatively high-frequency mutation gene, and other driver gene mutations are rare. In terms of immunohistochemistry, in pulmonary enteric adenocarcinoma, the positive rate was 88.2% (149/169) for CK7, 78.1% (132/169) for CDX2, 48.2% (82/170) for CK20 and 38.8% (66/170) for TTF1. As for clinical features, the average age of onset for pulmonary enteric adenocarcinoma was 62 years, male patients accounted for 56.5% (35/62), smokers accounted for 78.8% (41/52), and 41.4% (24/58) of the primary lesion was located in the upper lobe of the right lung. In terms of treatment, conventional non-small cell lung cancer (NSCLC) regimens rather than colorectal cancer regimens are now recommended. There is still an urgent need for more basic and clinical research, in-depth exploration of its molecular feature and pathogenesis from the level of omics and other aspects, to help diagnosis and differential diagnosis, and find the optimal chemotherapy regimen, possibly effective targeted therapy and even immunotherapy.

Metformin and ICG-001 Act Synergistically to Abrogate Cancer Stem Cells-Mediated Chemoresistance in Colorectal Cancer by Promoting Apoptosis and Autophagy.

Simple SummaryColorectal cancer (CRC) is one of the most frequently diagnosed and lethal malignancies. The majority of CRC patients experience disease relapse after the primary curative treatment strategy of surgery followed by 5FU-based chemotherapy. The presence of cancer stem-like cells (CSCs) is considered to be one of the contributing factors to therapy resistance and disease relapse in CRC. Previous studies implicated the role of the Wnt signaling pathway in the maintenance of the CSC phenotype. Therefore, in this study we explored a novel therapeutic strategy using metformin along with ICG-001, a Wnt signaling inhibitor, to abrogate CSC-mediated chemoresistance in CRC. We observed that metformin and ICG-001 abrogate stemness in a synergistic manner by promoting autophagy and apoptosis in 5FU-resistant CRC cells as well as in CRC patient-derived tumor organoids. Hence, metformin and ICG-001 can be used as part of a therapeutic strategy to overcome 5FU-mediated therapeutic resistance in CRC.Colorectal cancer (CRC) remains the third most frequently diagnosed cancer in the United States. The current treatment regimens for CRC include surgery followed by 5FU-based chemotherapy. Cancer stem-like cells (CSCs) have been implicated in 5FU-mediated chemoresistance, which leads to poor prognosis. In this study, we used metformin along with ICG-001, a Wnt signaling inhibitor, to abrogate CSC-mediated chemoresistance in CRC. We observed that 5FU-resistant (5FUR) CRC cells exhibited increased expression of CSC markers and enhanced spheroid formation. Genome-wide transcriptomic profiling analysis revealed that Wnt signaling, colorectal cancer metastasis signaling, etc., were enriched in 5FUR CRC cells. Accordingly, selective targeting of Wnt signaling using ICG-001 along with metformin abrogated CSC-mediated chemoresistance by decreasing the expression of CSC markers and promoting autophagy and apoptosis in a synergistic manner. We also observed that metformin and ICG-001 exhibited anti-tumor activity in CRC patient-derived tumor organoids. In conclusion, our study highlights that metformin and ICG-001 act synergistically and can be used as part of a therapeutic strategy to overcome 5FU-mediated therapeutic resistance in CRC.

Managing 5FU Cardiotoxicity in Colorectal Cancer Treatment.

Fluorouracil (5FU) is the backbone chemotherapy agent in the treatment of colorectal cancer (CRC). Cardiotoxicity represents an uncommon but serious side effect of treatment with 5FU. Here, we review the current literature on 5FU-cardiotoxicity in the setting of CRC specifically, with a focus on data from the modern era of combination chemotherapy. Despite decades of study, there is little consensus on risk factors and biomarkers for 5FU-cardiotoxicity, nor how patients with CRC should be managed following a cardiotoxicity event. Given the elevated risk of recurrent cardiotoxicity on rechallenge, the use of alternative regimens that do not contain 5FU is a critical aspect of management. Data on the cardiotoxicity risk and efficacy of non-5FU regimens in CRC are therefore reviewed in detail.

Thioredoxin 1 supports colorectal cancer cell survival and promotes migration and invasion under glucose deprivation through interaction with G6PD.

Overcoming energy stress is a critical step for cells in solid tumors. Under this stress microenvironment, cancer cells significantly alter their energy metabolism to maintain cell survival and even metastasis. Our previous studies have shown that thioredoxin-1 (Trx-1) expression is increased in colorectal cancer (CRC) and promotes cell proliferation. However, the exact role and mechanism of how Trx-1 is involved in energy stress are still unknown. Here, we observed that glucose deprivation of CRC cells led to cell death and promoted the migration and invasion, accompanied by upregulation of Trx-1. Increased Trx-1 supported CRC cell survival under glucose deprivation. Whereas knockdown of Trx-1 sensitized CRC cells to glucose deprivation-induced cell death and reversed glucose deprivation-induced migration, invasion, and epithelial-mesenchymal transition (EMT). Furthermore, we identified glucose-6-phosphate dehydrogenase (G6PD) interacting with Trx-1 by HuPortTM human protein chip, co-IP and co-localization. Trx-1 promoted G6PD protein expression and activity under glucose deprivation, thereby increasing nicotinamide adenine dinucleotide phosphate (NADPH) generation. Moreover, G6PD knockdown sensitized CRC cells to glucose deprivation-induced cell death and suppressed glucose deprivation-induced migration, invasion, and EMT. Inhibition of Trx-1 and G6PD, together with inhibition of glycolysis using 2-deoxy-D-glucose (2DG), resulted in significant anti-tumor effects in CRC xenografts in vivo. These findings demonstrate a novel mechanism and may represent a new effective therapeutic regimen for CRC.

Characterizing the Anticancer Treatment Trajectory and Pattern in Patients Receiving Chemotherapy for Cancer Using Harmonized Observational Databases: Retrospective Study.

BackgroundAccurate and rapid clinical decisions based on real-world evidence are essential for patients with cancer. However, the complexity of chemotherapy regimens for cancer impedes retrospective research that uses observational health databases.ObjectiveThe aim of this study is to compare the anticancer treatment trajectories and patterns of clinical events according to regimen type using the chemotherapy episodes determined by an algorithm.MethodsWe developed an algorithm to extract the regimen-level abstracted chemotherapy episodes from medication records in a conventional Observational Medical Outcomes Partnership (OMOP) common data model (CDM) database. The algorithm was validated on the Ajou University School Of Medicine (AUSOM) database by manual review of clinical notes. Using the algorithm, we extracted episodes of chemotherapy from patients in the EHR database and the claims database. We also developed an application software for visualizing the chemotherapy treatment patterns based on the treatment episodes in the OMOP-CDM database. Using this software, we generated the trends in the types of regimen used in the institutions, the patterns of the iterative chemotherapy use, and the trajectories of cancer treatment in two EHR-based OMOP-CDM databases. As a pilot study, the time of onset of chemotherapy-induced neutropenia according to regimen was measured using the AUSOM database. The anticancer treatment trajectories for patients with COVID-19 were also visualized based on the nationwide claims database.ResultsWe generated 178,360 treatment episodes for patients with colorectal, breast, and lung cancer for 85 different regimens. The algorithm precisely identified the type of chemotherapy regimen in 400 patients (average positive predictive value >98%). The trends in the use of routine clinical chemotherapy regimens from 2008-2018 were identified for 8236 patients. For a total of 12 regimens (those administered to the largest proportion of patients), the number of repeated treatments was concordant with the protocols for standard chemotherapy regimens for certain cases. In addition, the anticancer treatment trajectories for 8315 patients were shown, including 62 patients with COVID-19. A comparative analysis of neutropenia showed that its onset in colorectal cancer regimens tended to cluster between days 9-15, whereas it tended to cluster between days 2-8 for certain regimens for breast cancer or lung cancer.ConclusionsWe propose a method for generating chemotherapy episodes for introduction into the oncology extension module of the OMOP-CDM databases. These proof-of-concept studies demonstrated the usability, scalability, and interoperability of the proposed framework through a distributed research network.

Study on the role of nutritional assessment parameters in predicting chemotherapy Induced thrombocytopenia (CIT) with oxaliplatin based regimens in colorectal cancer

Rationale: The incidence of CIT caused by oxaliplatin based regimen is about 24% in colorectal cancer patients, which often cause chemotherapy delay, reduction, or even termination, and then affect the efficacy of chemotherapy. This study will focus on finding predictive nutritional assessment parameters on CIT caused by oxaliplatin based chemotherapy to find high risk CIT population.

Abstract PO-065: Utilization of optimized extracellular matrix substratum for inclusive capture of circulating tumor cells in stage IV colorectal cancer

Abstract Current methods to recover circulating tumour cells (CTCs) from the peripheral blood circulation of carcinoma patients rely principally on the expression of epithelial markers such as EpCAM, physical characteristics, and the absence of hematopoietic biomarkers. However, this strategy favours recovery of a homogeneous cell population with primarily differentiated epithelial characteristics. It fails to fully include those subpopulations that do not fit predictions and in particular does not properly capture cells that have stem-like characteristics or have undergone epithelial-mesenchymal transition (EMT). Yet these are often the cells that are most likely to give rise to successful metastasis and contribute to disease progression. We favour an approach that anticipates cellular heterogeneity, includes cells that have poor expression of differentiated characteristics, and relies on the very functional properties that are involved in successful negotiation of the route that culminates in metastasis. We therefore use a ‘tuned ECM’ (tECM) approach in which a complex ECM substratum is designed to extract and recover heterogeneous CTCs from the blood of patients with the cancer of interest, allowing subsequent single-cell analysis of cell behaviours to inform on features that have been shown to predict disease progression and metastasis. In the work described here we first used model colorectal cancer (CRC) cell lines, including those made resistant to drugs used in CRC regimens, to establish the best composition of ECM and full procedure to maximally capture cells for functional evaluation. For CRC we identified a defined mixture of collagen I and human plasma fibronectin as optimal for cell capture, providing a total recovery equivalent to complex ECM derived from tumor sources. In addition, this mixture accentuated the recovery of CRC cells made resistant to SN-38, the active metabolite of irinotecan. We then applied this approach to the recovery of CTCs from the blood from patients with stage IV CRC, using density centrifugation for prefractionation of nucleated blood cells followed by incubation on the tECM substratum. The captured cells could be immunostained in situ for both cytoplasmic and cell-surface markers and showed suitability for future assessment of cell behaviours in unfixed preparations. Optimisation of the capture-surface coating concentrations and subsequent fixation approach led to a 128-fold improvement in the CTC capture and identification from CRC patient blood. This optimised tECM approach offers promise for future inclusive recovery of heterogeneous CTC samples based on functional behaviours that relate to the metastastic process of the particular carcinoma, permitting further analyses including of chemokine pathways that are believed to be important in CRC metastasis. Citation Format: Deep Patel, Mala Bahl, Mario Valdes, Jonathan Blay. Utilization of optimized extracellular matrix substratum for inclusive capture of circulating tumor cells in stage IV colorectal cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-065.

Beyond bevacizumab: a review of targeted agents in metastatic small bowel adenocarcinoma.

Small bowel cancers are rare tumors with an incidence 50-100-fold less than colorectal cancer. These tumors carry a poor prognosis. Owing to its rarity, treatment of this disease, particularly in its advanced stages, has not been optimized and is derived mainly from treatment regimens for colorectal cancer. Based on recent studies bevacizumab, an antibody directed against vascular endothelial growth factor and used in the management of metastatic CRC, has been added to treatment guidelines for metastatic small bowel adenocarcinoma. We investigate in this review the evidence behind other targeted treatments that may be beneficial in the treatment of metastatic small bowel adenocarcinoma. These are agents against EGFR, VEGFR-2, HER2, and NTRK as well as immune checkpoint inhibitors. The last class of drugs appears to hold the greatest promise based on the preponderance of evidence supporting its use. However, overall data remains sparse. Results of studies currently underway will be valuable in shedding more light on the management of this aggressive cancer.

Fecal Microbiota Transplantation Prevents Intestinal Injury, Upregulation of Toll-Like Receptors, and 5-Fluorouracil/Oxaliplatin-Induced Toxicity in Colorectal Cancer.

FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin), a 5-fluorouracil (5-FU)-based chemotherapy regimen, is one of most common therapeutic regimens for colorectal cancer. However, intestinal mucositis is a common adverse effect for which no effective preventive strategies exist. Moreover, the efficacy and the safety of fecal microbiota transplants (FMT) in cancer patients treated with anti-neoplastic agents are still scant. We investigated the effect of FMT on FOLFOX-induced mucosal injury. BALB/c mice implanted with syngeneic CT26 colorectal adenocarcinoma cells were orally administered FMT daily during and two days after five-day injection of FOLFOX regimen for seven days. Administration of FOLFOX significantly induced marked levels of diarrhea and intestinal injury. FMT reduced the severity of diarrhea and intestinal mucositis. Additionally, the number of goblet cells and zonula occludens-1 decreased, while apoptotic and NF-κB-positive cells increased following FOLFOX treatment. The expression of toll-like receptors (TLRs), MyD88, and serum IL-6 were upregulated following FOLFOX treatment. These responses were attenuated following FMT. The disrupted fecal gut microbiota composition was also restored by FMT after FOLFOX treatment. Importantly, FMT did not cause bacteremia and safely alleviated FOLFOX-induced intestinal mucositis in colorectal cancer-bearing mice. The putative mechanism may involve the gut microbiota TLR-MyD88-NF-κB signaling pathway in mice with implanted colorectal carcinoma cells.

Predictors of Survival Among Colorectal Cancer Patients in a Low Incidence Area.

BackgroundColorectal cancer is the third most common malignancy in Saudi Arabia. The best therapeutic regimen for colorectal cancer is a matter of ongoing debate and data on its treatment in Saudi Arabia are limited.PurposeThe objective of this study was to explore the predictors of survival and to compare the risk of mortality among colorectal cancer patients treated with different therapeutic modalities.Patients and MethodsThe study utilized data from the electronic colorectal cancer registry of a university-affiliated tertiary care hospital. The Kaplan-Meier survival analysis was used to estimate the survival rates over 36 months of follow-up across rectal and colon cancer patients as well as different sociodemographic and medical characteristics. Bivariate and multiple Cox proportional-hazards regressions were conducted to estimate the risk of mortality among rectal and colon cancer patients undergoing different treatments.ResultsThe number of patients in the registry who were followed up for 36 months was 143 patients. The majority of patients had colon cancer (74.13%). Rectal cancer patients had generally better survival estimates compared to their colon cancer counterparts. Colon cancer patients treated with chemotherapy had a significantly lower risk of mortality controlling for the use of surgery, radiotherapy, and other variables including age, gender, stage of cancer, and family history of colorectal cancer (HR=0.33; P=0.03). Additionally, colon cancer patients with a family history of colorectal cancer had significantly higher risk of mortality (HR=3.40; P=0.02).ConclusionThe findings of this study highlight the value of chemotherapy in managing colon cancer patients.

Qualitative transcriptional signature for predicting pathological response of colorectal cancer to FOLFOX therapy.

FOLFOX (5‐fluorouracil, leucovorin and oxaliplatin) is one of the main chemotherapy regimens for colorectal cancer (CRC), but only half of CRC patients respond to this regimen. Using gene expression profiles of 96 metastatic CRC patients treated with FOLFOX, we first selected gene pairs whose within‐sample relative expression orderings (REO) were significantly associated with the response to FOLFOX using the exact binomial test. Then, from these gene pairs, we applied an optimization procedure to obtain a subset that achieved the largest F‐score in predicting pathological response of CRC to FOLFOX. The REO‐based qualitative transcriptional signature, consisting of five gene pairs, was developed in the training dataset consisting of 96 samples with an F‐score of 0.90. In an independent test dataset consisting of 25 samples with the response information, an F‐score of 0.82 was obtained. In three other independent survival datasets, the predicted responders showed significantly better progression‐free survival than the predicted non‐responders. In addition, the signature showed a better predictive performance than two published FOLFOX signatures across different datasets and is more suitable for CRC patients treated with FOLFOX than 5‐fluorouracil‐based signatures. In conclusion, the REO‐based qualitative transcriptional signature can accurately identify metastatic CRC patients who may benefit from the FOLFOX regimen.

Distinguishing Features of Cetuximab and Panitumumab in Colorectal Cancer and Other Solid Tumors.

Cetuximab and panitumumab are two distinct monoclonal antibodies (mAbs) targeting the epidermal growth factor receptor (EGFR), and both are widely used in combination with chemotherapy or as monotherapy to treat patients with RAS wild-type metastatic colorectal cancer. Although often considered interchangeable, the two antibodies have different molecular structures and can behave differently in clinically relevant ways. More specifically, as an immunoglobulin (Ig) G1 isotype mAb, cetuximab can elicit immune functions such as antibody-dependent cell-mediated cytotoxicity involving natural killer cells, T-cell recruitment to the tumor, and T-cell priming via dendritic cell maturation. Panitumumab, an IgG2 isotype mAb, does not possess these immune functions. Furthermore, the two antibodies have different binding sites on the EGFR, as evidenced by mutations on the extracellular domain that can confer resistance to one of the two therapeutics or to both. We consider a comparison of the properties of these two antibodies to represent a gap in the literature. We therefore compiled a detailed, evidence-based educational review of the known molecular, clinical, and functional differences between the two antibodies and concluded that they are distinct therapeutic agents that should be considered individually during treatment planning. Available data for one agent can only partly be extrapolated to the other. Looking to the future, the known immune activity of cetuximab may provide a rationale for this antibody as a combination partner with investigational chemotherapy plus immunotherapy regimens for colorectal cancer.

Peri- and postoperative nutrition in colorectal cancer patients

Peri- and postoperative nutrition in colorectal cancer patients Abstract. The long multimodal therapy regimens for colorectal cancer require a sufficient nutritional status of the patient. The "Enhanced Recovery After Surgery" concept aims for minimization of the interruption of nutrient intake and has been validated prospectively. Preoperative malnutrition as a strong risk factor for complications should be detected and treated early after cancer diagnosis by screening tools as the "Nutritional Risk Screening" (NRS-2002) or the "Malnutrition Universal Screening Tool" (MUST). High-caloric oral supplementation, enteral nutrition and parenteral nutrition are possible measures, which should be escalated stepwise. The recent concept of "prehabilitation" additionally includes short‑term optimization of the physical and psychological status. Postoperative attention should be paid to possible deficiency syndromes of single nutrients due to reduced resorption after bowel segment resection or stoma creation. Risk- and preventive factors in primary prevention of colorectal carcinoma are well-known, in secondary prevention knowledge is less clear. There is only low evidence for a positive effect of omega-3 fatty acids, coffee, high-fiber diet and vitamin D in secondary prevention of colorectal carcinoma, requiring further studies.

Early experience with Watson for oncology in Korean patients with colorectal cancer.

BackgroundWatson for oncology (WFO) is a cognitive computing system providing decision support. We evaluated the concordance rates between the treatment options determined by WFO and those determined by a multidisciplinary team (MDT).MethodsWe reviewed the medical charts of patients diagnosed with colorectal cancer who visited the MDT at a single tertiary medical center from November 2016 to April 2017. WFO classified the treatment options for specific patients into three categories: ‘Recommended’, ‘For consideration’, and ‘Not recommended’. Concordance rates between the WFO- and MDT-determined chemotherapy options, and the factors that potentially influence the concordance rate, were analyzed.ResultsSixty-nine patients with colorectal cancer met with the MDT from Nov. 2016 to Feb. 2017. The mean age of the patients was 62 years (range: 34–86 years), and more patients were male (47/69) than female. Of the 69 patients, 51 (73.9%) were diagnosed with colon cancer, of whom 46.4% received the same regimen recommendation from WFO (‘Recommended’) as they did from the MDT. After inclusion of the ‘For consideration’ category from WFO, the concordance rate increased to 87.0%. The concordance rate between MDT and NCCN guidelines was 97.1%, and that between the WFO and NCCN guidelines was 88.4%. The concordance rates between WFO and MDT were significantly lower in patients with stage II, IIIC, or IV disease (P<0.001), and the colorectal cancer stage was the only statistically significant factor discriminating between WFO and MDT.ConclusionsThe concordance rate between chemotherapy regimens for colorectal cancer determined by MDT versus WFO recommendations was 46.4%. After including the ‘For consideration’ category from WFO, the concordance rate increased to 88.4%. Further modification and improvement of the WFO prioritizing algorithm used to recommend treatment may increase the usefulness of WFO in the clinic.

Meta-Analysis of 5-Fluorouracil-Based Chemotherapy Combined With Traditional Chinese Medicines for Colorectal Cancer Treatment.

This meta-analysis evaluates the clinical evidence for the addition of traditional Chinese medicines (TCMs) to 5-fluorouracil (5-FU)-based regimens for colorectal cancer (CRC) in terms of tumor response rate (TRR). Five electronic databases were searched for randomized controlled trials of 5-FU-based chemotherapy combined with TCMs compared to the same 5-FU-based regimen. Forty-five randomized controlled trials were involved in this study, and all the data were analyzed by Stata software (version 14.0). Our results suggested that the TRR of the group with TCMs combined with 5-FU-based regimens was higher than that in the group with 5-FU regimens alone (risk ratio [RR] 1.36 [1.25-1.49], I2 = 0%). Furthermore, both nonoral administration (RR 1.51 [1.29-1.76], I2 = 0%) and oral administration (RR 1.31 [1.18-1.45], I2 = 0%) of TCMs showed benefits to the CRC treatment. Further sensitivity analysis of specific plant-based TCMs found that fuling, sheshecao, banzhilian, eshu, baizhu, huangqi, yiyiren, and dangshen had significantly higher contributions to the results of the risk ratio. Therefore, TCMs may have the potential to improve the efficacy of 5-FU-based chemotherapy for CRC.

Adherence to a Standardized Chemotherapy Order form for Colorectal Cancer in a Referral Teaching Hospital, Mashhad, Iran.

Using standardized forms for prescription and administration of medications is one of the main solutions for reducing medication errors in the chemotherapy process. Considering the high prevalence and mortality rate of colorectal cancer, in this study we tried to design and validate a standard printed form and evaluate oncologists' and nurses' adherence to this form. This cross-sectional study was performed in Omid hospital, Mashhad, Iran from January 2015 to October 2015. A Chemotherapy form including various demographic and clinical parameters and approved chemotherapy regimens for colorectal cancer was designed by the clinical pharmacist and validated by clinical oncologists working in this center. All eligible patients admitted in this center during this period of time were included in the study. Adherence of the oncologists and nurses to this form and probable medication errors were identified by the pharmacy student. Sixty-seven patients with colorectal cancer and a total of 251 chemotherapy courses were evaluated. All patients received regimens compatible with developed form but in 206 courses (98.56%) of chemotherapy dosing error happened and in most of cases patients received lower than calculated dose (37.8%). Three errors occurred in administration step by nurses which they infused the medication in shorter than recommended duration. In general, oncologists' adherence with developed form for chemotherapy of colorectal cancer was relatively high, except in dose calculation. Avoiding from rounding the calculated medications' doses and precise calculation of patients' body surface area can prevent most of medication errors and reduce risk of adverse drug reaction occurrence.

Effects of Proton Pump Inhibitors on FOLFOX and CapeOx Regimens in Colorectal Cancer

BackgroundFirst-line adjuvant chemotherapy options for early-stage colorectal cancer (CRC) include CapeOx (capecitabine, intravenous oxaliplatin) and FOLFOX (intravenous 5-fluorouracil, leucovorin, oxaliplatin). Capecitabine is an oral prodrug analog of 5-fluorouracil, and recent studies have suggested that proton pump inhibitors (PPIs) may detrimentally affect capecitabine efficacy. Conversely, some literature suggests that PPIs may negatively affect CRC itself. To gain insight into the nature of PPIs’ effect on capecitabine and CRC, we investigated their effects on effectiveness of CapeOx versus FOLFOX chemotherapy. Patients and MethodsWe conducted a retrospective chart review of 389 patients with stage II-III CRC who received adjuvant CapeOx or FOLFOX from 2004 to 2013. Information regarding PPI receipt, chemotherapy, and patient outcomes from medical records was analyzed. ResultsThree-year recurrence-free survival was significantly lower in CapeOx-treated PPI recipients than non-PPI recipients (69.5 vs. 82.6%; P = .029). Unadjusted analysis showed that CapeOx-treated PPI recipients were twice as likely to experience cancer recurrence or death as CapeOx-treated non-PPI recipients (hazard ratio = 2.03; 95% confidence interval, 1.06-3.88; P = .033). FOLFOX-treated PPI recipients had a non–statistically significant difference in 3-year recurrence-free survival versus non-PPI recipients (82.9 vs. 61.7%; P = .066) and a non–statistically significant difference in recurrence/death (hazard ratio = 0.51; 95% confidence interval, 0.25-1.06; P = .071). No significant differences were seen in overall survival between groups. ConclusionOur results suggest PPIs negatively affected recurrence-free survival in CapeOx-treated CRC patients and yielded no significant effects among FOLFOX-treated patients, potentially implicating a pharmacokinetic interaction between PPIs and capecitabine. No overall survival effects were seen. Given PPIs’ widespread use, further studies are required to corroborate our findings.

Lidocaine inhibits proliferation and induces apoptosis in colorectal cancer cells by upregulating mir-520a-3p and targeting EGFR

Lidocaine is a conventional local anesthetic which is shown antiproliferative of colorectal cancer (CRC) in patients. MicroRNAs (miRNAs) have been consistently demonstrated to be involved in CRC, and miR-520a-3p could suppress CRC migration, promote apoptosis by targeting epidermal growth factor receptor (EGFR). However, the mechanism by which lidocaine regulated CRC proliferation and apoptosis remains unknown. In this study, quantitative RT-PCR were used to measure miR-520a-3p and EGFR expression levels, and western blotting assays ware performed to measure EGFR expression in CRC cells. Luciferase reporter assay was employed to validate the direct targeting of EGFR by miR-520a-3p. Cell proliferation and apoptosis assays ware utilized to analyze the role of lidocaine in CRC cells. The results indicated that 500 and 1000 μM lidocaine over 24 h inhibited proliferation and induced apoptosis of CRC cells. Compared with the control group, the expression of EGFR was suppressed by lidocaine (500 μM) in CRC cells. Furthermore, miR-520a-3p could directly targets EGFR in CRC cells. Lidocaine (500 μM) increased the expression of miR-520a-3p and rescued the reduction of miR-520a-3p caused by miR-520a-3p inhibitor. The results suggested that lidocaine could suppress the expression of EGFR by upregulating miR-520a-3p, and it could induce apoptosis and inhibit proliferation in CRC cells. Lidocaine may serve as potential therapeutic regimen for colorectal cancer.

Role of antiangiogenic agents in the treatment of metastatic colorectal cancer

This review covers the latest data on antiangiogenic agents used in patients with colorectal cancer. In this article, we describe drugs that have already been included into therapy regimens for colorectal cancer and vascular endothelial growth factor (VEGF) inhibitors that have been approved for other indications. Targeted drugs with a similar mechanism of action that are currently in clinical trials are discussed separately. VEGF-inhibitors are one of the main groups of targeted drugs for colorectal cancer with an acceptable toxicity profile, which can be used both in combination with chemotherapeutic agents and as maintenance treatment. Moreover, these drugs are not dependent on mutational status, which is a significant advantage.