Relationship between Expression of Runt-related Transcription Factor 3 and Enhancer of zeste Homolog 2 Proteins and Sensitivity to Neoadjuvant Chemotherapy in Locally Advanced Rectal Cancer / 中国医学科学院学报

Objective To investigate the expression and correlation of Runt-related transcription factor 3(RUNX3)and enhancer of zeste homolog 2(EZH2)in rectal cancer,and to reveal the relationship between the expression of RUNX3 and EZH2 and the sensitivity of XELOX regimen to neoadjuvant chemotherapy in locally advanced rectal cancer patients. Methods The carcinoma and paracancerous tissues of 31 patients with rectal adenocarcinoma and no preoperative antitumor therapy were selected as cancer group and paracancer group,respectively.The relative mRNA levels of RUNX3 and EZH2 in the two groups were measured by real-time quantitative reverse transcription-polymerase chain reaction,and the protein levels were determined by immunohistochemical assay.The expression of RUNX3 and EZH2 was compared between cancer tissue and paracancerous tissue.The pre-treatment wax blocks of 26 patients with locally advanced rectal cancer who received 3 cycles of XELOX regimen as neoadjuvant chemotherapy before surgery were selected as the pre-neoadjuvant therapy group,and the postoperative pathological wax blocks were selected as the post-neoadjuvant treatment group.Tumor regression grade(TRG)was determined to evaluate the efficacy of neoadjuvant therapy.Immunohistochemical assay was used to detect the protein levels of RUNX3 and EZH2 in the two groups,and then the relationship between the expression patterns of the two proteins and the efficacy of neoadjuvant chemotherapy was analyzed. Results Compared with paracancerous tissue,the cancer tissue showed down-regulated mRNA level and reduced positive protein expression rate of RUNX3,while up-regulated mRNA level(

Efficacy and safety of XELOX therapy in comparison with capecitabine monotherapy in adjuvant chemotherapy for elderly patients with colorectal cancer / 中国临床药理学与治疗学

AIM: To investigate the efficacy and safety of the XELOX therapy (capecitabine plus oxaliplatin) versus capecitabine monotherapy in adjuvant chemotherapy for elderly patients with colorectal cancer. METHODS: This study included 195 elderly patients with early colorectal cancer (60-82 years old) who underwent R0 surgical resection from January 2010 to December 2017 in Zhengzhou People's Hospital. Patients received either adjuvant chemotherapy with capecitabine monotherapy or XELOX therapy after surgery (selective adjuvant chemotherapy based on patient ECOG score, physical status, physician assessment, patient tolerance, and willingness). The baseline clinical data were collected through the hospital case system and patients were followed up according to the trial protocol. Disease-free survival (DFS) and overall survival (OS) were analyzed by Kaplan-Meier survival analysis. Cox risk ratio model was established to evaluate the efficacy of different adjuvant chemotherapy regimens with the same risk factors. Adverse reactions above level 2 (according to CTCAE 4.0) were recorded for safety analysis. RESULTS:The median follow-up of the study was 5.75 years (the follow-up time range: 0.30-7.50 years). The efficacy was evaluated in 195 patients enrolled in the study. The median disease-free survival (mDFS) was 5.0 years in the overall patient population, and the mDFS in the XELOX group was 5.5 years, significantly higher than the mDFS of the capecitabine monotherapy group for 3.6 years (P=0.047, 95%CI: 2.06-5.14). The overall median overall survival (mOS) was 7.1 years, and the mOS of the XELOX group was 7.1 years, significantly higher than the median total of the capecitabine monotherapy group mOS 4.5 years (P=0.021, 95% CI: 3.30-5.70). With the same risk factors, when the patients were younger than 70 years old, both the DFS (HR=0.74, P=0.036) and OS (HR=0.78, P=0.041) patients could benefit from the XELOX regimen; when the patients ≥70 years old, only DFS (HR=0.77, P=0.035) could benefit from the XELOX therapy. Regardless of the patient's comorbidities, the patient's DFS and OS benefit from the XELOX therapy. However, patient's DFS and OS can benefit from XELOX only when the number of lymph nodes examined was less than 12 nodes and the number of cycles of patients receiving adjuvant chemotherapy was ≥6 cycles. In terms of adverse reactions, the incidence of neutropenia (61.54% vs. 39.74%, P=0.003) and neurotoxicity (65.81% vs. 0%) were significantly higher in the XELOX therapy than the capecitabine monotherapy regimen. Other adverse reactions such as diarrhea, stomatitis, thrombocytopenia, hand-foot syndrome, anemia, nausea and vomiting, increased AST/ALT, and hair loss were not significantly different between the two groups (P>0.05). CONCLUSION: The XELOX therapy does not significantly increase adverse events in elderly patients, and elderly patients (age<70 years old) who combine oxaliplatin on the basis of capecitabine can significantly benefit from DFS and OS, but when the patients were≥70 years old, only DFS can benefit, while OS cannot.

A Single Arm, Phase II Study of Simvastatin Plus XELOX and Bevacizumab as First-Line Chemotherapy in Metastatic Colorectal Cancer Patients / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Simvastatin has demonstrated anti-tumor activity in preclinical studies via tumor cell senescence, apoptosis, and anti-angiogenesis. This phase II trial evaluated the efficacy and toxicity profile of conventional XELOX and bevacizumab chemotherapy plus simvastatin in metastatic colorectal cancer patients (MCRC). MATERIALS AND METHODS: Patients with MCRC received first-line XELOX in 3-week treatment cycles of intravenous oxaliplatin 130 mg/m² plus bevacizumab 7.5 mg/kg (day 1), followed by oral capecitabine 1,000 mg/m² twice daily (day 1-14). Simvastatin 80 mg tablets were taken orally once daily every day during the period of chemotherapy. The primary endpoint was progression-free survival (PFS). Secondary endpoints were response rate, duration of response, overall survival (OS), time to progression, and toxicity. RESULTS: From January 2014 to April 2015, 60 patients were enrolled and 55 patients were evaluable for tumor response. The median follow-up duration was 30.1 months (range, 28.5 to 31.7 months). The median PFS was 10.4 months (95% confidence interval [CI], 9.6 to 11.1). The median OS of all patients was 19.0 months (95% CI, 11.9 to 26.0). The disease-control rate and overall response rate were 88.3% (95% CI, 74 to 96) and 58.3% (95% CI, 44 to 77), respectively, by intent-to-treat protocol analysis. There was one complete response and 34 partial responses. One patient experienced grade 3 creatine kinase elevation and liver enzyme elevation. CONCLUSION: Based on the current study, the addition of 80 mg simvastatin to XELOX and bevacizumab showed comparable clinical efficacy in patients with MCRC as first-line chemotherapy and did not increase toxicity.

Preoperative short course radiotherapy with concurrent and consolidation chemotherapies followed by delayed surgery in locally advanced rectal cancer: preliminary results

PURPOSE: This study aimed to assess complications and outcomes of a new approach, that is, combining short course radiotherapy (SRT), concurrent and consolidative chemotherapies, and delayed surgery. MATERIALS AND METHODS: In this single arm phase II prospective clinical trial, patients with T3-4 or N+ M0 rectal adenocarcinoma were enrolled. Patients who received induction chemotherapy or previous pelvic radiotherapy were excluded. Study protocol consisted of three-dimensional conformal SRT (25 Gy in 5 fractions in 1 week) with concurrent and consolidation chemotherapies including capecitabine and oxaliplatin. Total mesorectal excision was done at least 8 weeks after the last fraction of radiotherapy. Primary outcome was complete pathologic response and secondary outcomes were treatment related complications. RESULTS: Thirty-three patients completed the planned preoperative chemoradiation and 26 of them underwent surgery (24 low anterior resection and 2 abdominoperineal resection). Acute proctitis grades 2 and 3 were seen in 11 (33.3%) and 7 (21.2%) patients, respectively. There were no grades 3 and 4 subacute hematologic and non-hematologic (genitourinary and peripheral neuropathy) toxicities and perioperative morbidities such as anastomose leakage. Grade 2 or higher late toxicities were observed among 29.6% of the patients. Complete pathologic response was achieved in 8 (30.8%) patients who underwent surgery. The 3-year overall survival and local control rates were 65% and 94%, respectively. CONCLUSION: This study showed that SRT combined with concurrent and consolidation chemotherapies followed by delayed surgery is not only feasible and tolerable without significant toxicity but also, associated with promising complete pathologic response rates.

Effect of preoperative chemotherapy with XELOX and psychological intervention on surgical treatment of advanced gastric cancer / 中国生化药物杂志

Objective To investigate the clinical effect of preoperative XELOX chemotherapy combined with psychological intervention on patients with advanced gastric cancer.Methods The control group, advanced gastric cancer patients underwent surgical treatment, XELOX chemotherapy was given before the operation.The study group was treated with psychological intervention on the basis of the treatment of the control group.The clinical efficacy and adverse reactions of two patients with advanced gastric cancer were recorded.Results Study group five years survival rate(63.83%),disease-free survival(42.55%),no advanced end point event probability(46.81%)was significantly higher than the control group(five and 44.68%year survival rate, disease-free survival rate was 23.40%,no advanced end point event probability 27.66%),data comparison study group P<0.05;wound healing reaction indigestion, gastrointestinal reaction, infection, oral mucositis incidence was significantly lower than the control group(P<0.05).Conclusion In the preoperative XELOX chemotherapy combined with surgical treatment on the basis of advanced gastric cancer with the corresponding psychological intervention can effectively improve the curative effect and prognosis,has positive significance to guarantee the quality of life of patients, life safety.

Advances in bevacizumab combined with XELOX regimen in the treament of metastatic colorectal cancer / 实用肿瘤学杂志

Colorectal cancer is a common malignant tumor in digestive system ,with an increasing inci-dence rate and case fatality rate all over the world in recent decades .At present,chemotherapy still plays a very important role in the treatment of advanced colorectal cancer .Targeted therapy brings new hope to patients ,and new chemotherapy drugs and targeted drugs have been widely used in clinics .Patient′s life quality has been great-ly improved,survival time has been significantly prolonged ,the combination of chemotherapy and targeted therapy has also become a hot research area in the treatment of metastatic colorectal cancer .XELOX ( capecitabine plus oxaliplatin)as a first-line chemotherapy regimen in treating metastatic colorectal cancer (mCRC)can obtain good therapeutic effect ,the side effects of XELOX are light and well tolerated;Bevacizumab ,as a new type of targeted anti-tumor drugs ,shows a good effect in inhibiting tumor growth and reducing its hematogenous spread risk .Bev-acizumab in combination with XELOX regimen for treating mCRC has been widely investigated and reported .This review gives a brief summary on the efficacy and safety of the combined administration of Bevacizumab and XE -LOX.

Meta-analysis of regimen SOX versus XELOX in treatment of Chinese patients with advanced gastric carcinoma / 中国生化药物杂志

Objective To compare clinical outcome and adverse reactions between the regimens SOX and XELOX for chemotherapy of advanced gastric carcinoma in Chinese population.Methods The original articles on randomized controlled trials ( RCTs) comparing the chemotherapy of SOX and XELOX in Chinese patients with advanced gastric carcinoma were recruited from the PUBMED, WANFANG, VIP and CNKI databases.The quality of the selected trials were assessed by JADAD method.Meta-analysis about the efficacy and safety of the two chemotherapy methods was performed by Rev Man 5.2.0 software ( Cochrane-information Management System) .Results Eight RCT studies were recruited in our work, including 293 patients in the SOX treatment group and 310 in the XELOX treatment group.The analysis results showed that there was no significant difference in the effect of the two chemotherapy methods (OR=1.19, 95%CI:0.86-1.64,P=0.29), and referred to the safety evaluation, the stomatitis (OR=2.29, 95%CI:1.74-4.89, P<0.0001) incidence in SOX treatment group was higher than XELOX treatment group, and in total, there was no significant difference in adverse reaction incidence of the two chemotherapy methods(OR =0.88, 95%CI: 0.66-1.19, P =0.41).Conclusion In the chemotherapy of advanced gastric carcinoma in Chinese population, there is no significant difference in clinical response rate between SOX and XELOX, and the stomatitis incidence of SOX is significantly higher than that of XELOX.

XELOX plus bevacizumab as a ifrst-ine treatment for Chinese patients with metastatic colorectal cancer:a retrospective study / 中国生化药物杂志

Objective To observe the efifcacy and safety of XELOX plus bevacizumab as a ifrst-ine treatment for Chinese patients with metastatic colorectal cancer. Methods In this study, we retrospectively reviewed cases in which XELOX plus bevacizumab were administered in order to evaluate its efifcacy and safety in clinical practice.In total, 40 patients with mCRC who presented at Fuchu Hospital received XELOX plus bevacizumab as a ifrst?line treatment from September, 2009 to April, 2012. Eligible patients had histologically conifrmed mCRC. XELOX consisted of a 2-h intravenous infusion of oxaliplatin 130 mg/m 2 on day 1 plus oral capecitabine 1,000 mg/m 2 twice daily for two weeks of athree?week cycle. Overall survival (OS) and survival benefit were analyzed when patients continued with XELOX plus bevacizumab beyond disease progression. Results The median progression?free survival (PFS) was 290 days [95%conif-dence interval (CI):222?409 days] and the median OS was 816 days (95%CI:490?842 days). The response rate (RR:complete plus partial response) was 67.5%, and the disease control rate (RR plus stable disease) was 90%. Conclusion XELOX plus bevacizumab may be considered a routine ifrst?line treatment option for patients with mCRC.

Study of lentinan's promotion on XELOX regimen's curative effects on advanced gastric cancer / 中国生化药物杂志

Objective To study lentinan’s promotion on XELOX regimen’s curative effects on advanced gastric cancer. Method Cases with advanced gastric cancer were divided into observation group and control group according their therapy method. The curative effects, side effects, WBC, lymphocyte subsets, NK cells and quality of life were compared. Results The difference of disease control rates in two groups were not significant (P=0.091). The incidences of side effects in observation group were significantlly lower than in control group (P<0.05). The observation group’s WBC, Lym, CD 3+, CD 4+, CD 8+, NK cells and quality of life were significantly higher than in control group(P<0.05). Conclusion Lentinan could significantly promote gastric cancer patients’immunity and lessen side effects. It can promote XELOX regimen’s curative effects on gastric cancer and improve quality of life.

A Case of Oxaliplatin-Related Ocular Toxicity

PURPOSE: To report a case of oxaliplatin (Eloxatin(R))-related ocular toxicity in a patient with advanced stomach cancer. CASE SUMMARY: A 43-year-old female with advanced stomach cancer experienced visual symptoms during the treatment with oxaliplatin on a XELOX schedule (a combination of oxaliplatin and capecitabine). After 1 cycle of chemotherapy, she complained of blurred vision and visual field defects in both eyes. Visual field tests showed a bilateral concentric field defect and the electroretinogram revealed a marked reduction of responses in both eyes. On the second cycle of chemotherapy, oxaliplatin was discontinued due to suspicious ocular toxicity. Her visual symptoms improved and visual field test showed normal results 1 month after oxaliplatin discontinuation. However, 3 months after oxaliplatin discontinuation, electroretinogram remained abnormal despite the progressive improvement. CONCLUSIONS: Platinum-based antineoplastic agents such as oxaliplatin should be administered with caution because oxaliplatin can cause damage to the retinal photoreceptors and the optic nerve. Early detection of ocular toxicity and discontinuation of oxaliplatin therapy could prevent severe and irreversible visual loss.