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According to the data of the world statistics, gastric cancer (GC) occupies the 5th place by morbidity and the 3rd one by mortality among malignant neoplasms. A significant proportion of patients are elderly patients, the proportion of which in real clinical practice can reach up to 60%. Ramucirumab is among the standards of second-line drug therapy both in monotherapy and in combination with paclitaxel. The feasibility of prescribing ramucirumab to patients with disseminated cancer of the elderly and its satisfactory tolerability is shown in a subgroup analysis of the REGARD and RAINBOW studies. The use of paclitaxel, included in the standard first-line regimens, may be limited by persistent neurotoxicity, a side effect of platinum derivatives. In this regard, the effectiveness of the combination of ramucirumab with the FOLFIRI regimen as a second-line therapy began to be studied. The article presents a clinical case of achieving a partial effect on the second-line therapy with ramucirumab with FOLFIRI regimen in a 74-year-old patient with HER2-negative gastric adenocarcinoma while registering rapid progression after 4 courses of first-line chemotherapy in XELOX regimen. Tolerability of the second line was acceptable: asthenia grade 1, stomatitis grade 1-2, neutropenia grade 3 were observed, so the irinotecan dose was reduced to 165 mg/m2. By June 2021, there were 10 28-day cycles of treatment, which is ongoing. The duration of disease control in the second line therapy was 11+ months, of which 9+ months – on the background of FOLFIRI regimen drug therapy with ramucirumab.

Background The trial hypothesis was that, in a resource-constrained situation, short-course radiotherapy would improve treatment compliance compared with conventional chemoradiotherapy for locally advanced rectal cancer, without compromising oncological outcomes. Methods In this open-label RCT, patients with cT3, cT4 or node-positive non-metastatic rectal cancer were allocated randomly to 5 × 5 Gy radiotherapy and two cycles of XELOX (arm A) or chemoradiotherapy with concurrent capecitabine (arm B), followed by total mesorectal excision in both arms. All patients received a further six cycles of adjuvant chemotherapy with the XELOX regimen. The primary endpoint was treatment compliance, defined as the ability to complete planned treatment, including neoadjuvant radiochemotherapy, surgery, and adjuvant chemotherapy to a dose of six cycles. Results Of 162 allocated patients, 140 were eligible for analysis: 69 in arm A and 71 in arm B. Compliance with planned treatment (primary endpoint) was greater in arm A (63 versus 41 per cent; P = 0.005). The incidence of acute toxicities of neoadjuvant therapy was similar (haematological: 28 versus 32 per cent, P = 0.533; gastrointestinal: 14 versus 21 per cent, P = 0.305; grade III–IV: 2 versus 4 per cent, P = 1.000). Delays in radiotherapy were less common in arm A (9 versus 45 per cent; P < 0.001), and overall times for completion of neoadjuvant treatment were shorter (P < 0.001). The rates of R0 resection (87 versus 90 per cent; P = 0.554), sphincter preservation (32 versus 35 per cent; P = 0.708), pathological complete response (12 versus 10 per cent; P = 0.740), and overall tumour downstaging (75 versus 75 per cent; P = 0.920) were similar. Downstaging of the primary tumour (ypT) was more common in arm A (P = 0.044). There was no difference in postoperative complications between trial arms (P = 0.838). Conclusion Reduced treatment delays and a higher rate of compliance were observed with treatment for short-course radiotherapy with consolidation chemotherapy, with no difference in early oncological surgical outcomes. In time- and resource-constrained rectal cancer units in developing countries, short-course radiotherapy should be the standard of care.

OBJECTIVE The aim: To evaluate and analyze early and late results of treatment of patients with rectal cancer after chemotherapy. PATIENTS AND METHODS Materials and methods: The study is based on the results of observation of 779 patients with stage II, III and IV rectal cancer (RC) who were divided into groups according to the chemotherapy treatment. RESULTS Results: In the course of chemotherapy treatment of RC patients, most of them received the FOLFOX regimen treatment - 87 patients (43.5%). 40 people (20%) received Mayo regimen. 36 patients (18%) underwent FOLFIRI regimen. Another 33 patients received the XELOX regimen chemotherapy (16.5%). In four cases, patients underwent Tegafur monotherapy (2%). CONCLUSION Conclusions: The obtained data for patients with stage III RC showed that at all studied time intervals, the highest percentage of surviving patients was recorded in those who received chemotherapeutic treatment according to the FOLFOX regimen. In patients with stage II RC, the most ef f ective was Mejo regimen - 30.7% (survived patients for the 5 year observation).

Purpose Colorectal cancer is becoming an increasing concern in the middle-aged population of Iran. This study aimed to compare the preliminary results of short-course and long-course neoadjuvant chemoradiotherapy treatment for rectal cancer patients. Materials and Methods In this clinical trial we recruited patients with rectal adenocarcinoma located from 5 cm to 15 cm above the anal verge. Patients in group I (short-course) received three-dimensional conformational radiotherapy with a dose of 25 Gy/5 fractions in 1 week plus concurrent XELOX regimen (capecitabine 625 mg/m2 from day 1–5 twice daily and oxaliplatin 50 mg/m2 on day 1 once daily). Patients in group II (long-course) received a total dose of 50–50.4 Gy/25–28 fractions for 5 to 5.5 weeks plus capecitabine 825 mg/m2 twice daily. Both groups underwent consolidation chemotherapy followed by delayed surgery at least 8 weeks after radiotherapy completion. The pathological response was assessed with tumor regression grade. Results In this preliminary report on complications and pathological response, 66 patients were randomized into two study groups. Mean duration of radiotherapy in groups I and II was 5 ± 1 days (range, 5 to 8 days) and 38 ± 6 days (range, 30 to 58 days). The median follow-up was 18 months. Pathological complete response was achieved in 32.3% and 23.1% of patients in the short-course and long-course groups, respectively (p = 0.558). Overall, acute grade 3 or higher treatment-related toxicities occurred in 24.2% and 22.2% of patients in group I and II, respectively (p = 0.551). No acute grade 4 or 5 adverse events were observed in either group except one grade 4 hematologic toxicity that was seen in group II. Within one month of surgery, no significant difference was seen regarding grade ≥3 postoperative complications (p = 0.333). Conclusion For patients with rectal cancer located at least 5 cm above the anal verge, short-course radiotherapy with concurrent and consolidation chemotherapy and delayed surgery is not different in terms of acute toxicity, postoperative morbidity, complete resection, and pathological response compared to long-course chemoradiotherapy.

Background: Small bowel adenocarcinoma are relatively rare tumors of the digestive system. Due to the lack of specific screening methods, patients are often diagnosed at an advanced stage. At present, there is no specific surgical guidance and chemotherapy regimen for small bowel adenocarcinoma. Here, we report a rare small bowel adenocarcinoma case with mesenteric vascular embolization and microsatellite instability, in which palliative surgery combined with chemotherapy and anti-Programmed cell death protein 1(PD-1) therapy resulted in complete remission.Case Presentation: The patient was a 55-year-old man who was admitted for suspected small bowel adenocarcinoma combined with incomplete ileus, mesenteric vascular occlusion and distant metastasis. We performed palliative surgery to remove adenocarcinoma as well as relieve obstruction. Then according to the pathological and immunohistochemical results (Stage IV and microsatellite instability), we used XELOX regimen combined with anti-PD-1 therapy. In last 2 years follow up, this patient achieved complete remission.Conclusions: The possibility of small intestinal tumor should be considered in patients with mesenteric vascular obstruction. PD-1 blockade is an effective therapy for small bowel adenocarcinoma with microsatellite instability.

Background Real-world safety and effectiveness data for trastuzumab plus chemotherapy treatment of patients with HER2-positive metastatic gastric cancer (mGC) in China are lacking. Patients and Methods EVIDENCE was a prospective, multicenter, noninterventional registry study evaluating the safety and effectiveness of trastuzumab in five cohorts of Chinese patients with gastric cancer, stratified by HER2 status and trastuzumab treatment. Effectiveness was analyzed for cohorts I (HER2-positive, trastuzumab treated), II (HER2-positive, trastuzumab untreated), and IV (HER2-negative, trastuzumab untreated); trastuzumab-related adverse events (AEs) were analyzed for cohort I. Results Cohorts I, II, and IV included 174, 113, and 422 patients, respectively. Most patients received first-line chemotherapy (87.6%). Median overall survival (OS1) for first-line treatment was 22.3, 17.2, and 17.4 months in cohorts I, II, and IV, respectively. After excluding patients who had surgery, respective median OS1 was 19.9, 15.3, and 12.9 months. Respective first-line progression-free survival (PFS1) was 8.2, 6.9, and 6.2 months; and respective first-line response rates (RR) were 51.7%, 18.4%, and 32.8%. Cohort I was significantly favored over cohort II for propensity score–matched first-line median OS1 (hazard ratio [HR], 0.61), PFS1 (HR, 0.64), and RR (odds ratio, 4.93). Trastuzumab-related AEs, grade 3–5 AEs, serious AEs, and AEs with a fatal outcome occurred in 23.6%, 3.4%, 2.3%, and 0.6% of cohort I patients, respectively. Conclusion Safety profiles were consistent with those known for trastuzumab and chemotherapy; trastuzumab treatment improved outcomes. Our study provides real-world data supporting first-line trastuzumab plus chemotherapy in Chinese patients with HER2-positive mGC. Implications for Practice This prospective, noninterventional registry study aimed to provide safety and effectiveness data for the use of trastuzumab in combination with chemotherapy in Chinese patients with HER2-positive metastatic gastric cancer (mGC) from the real-world clinical setting. Trastuzumab plus first-line chemotherapy was shown to be safe and to improve outcomes when compared with patients treated with chemotherapy alone. Trastuzumab was effective within a range of treatment regimens; subgroup analysis showed that trastuzumab paired most effectively with the XELOX regimen. This study provides real-world clinical safety and effectiveness data supporting the use of trastuzumab in the treatment of Chinese patients with HER2-positive mGC.

Objective: The aim of this study was to compare the clinical efficacy of neoadjuvant chemoradiotherapy (NACRT) combined with postoperative adjuvant XELOX (Oxaliplatin +Capecitabine) chemotherapy and postoperative adjuvant chemotherapy (ACT) with XELOX for local advanced gastric cancer (LAGC). Methods: In this prospectively randomized trial, we investigated the effect of NACRT combined with postoperative ACT for LAGC. 60 patients were randomly divided into NACRT group and ACT group, with 30 patients in each group. Patients in NACRT group were given three-dimensional conformal radiotherapy (45 Gy/1.8 Gy/f) accompanied by synchronous XELOX of two cycles, followed by surgery, and then postoperative adjuvant XELOX chemotherapy of four cycles was performed. Patients in ACT group received surgery in advance, and then XELOX chemotherapy of six cycles was given. Results: The objective response rate of NACRT was 76.7%. The overall incidence of postoperative complications in NACRT group was not significantly different from that in ACT group (23.1% vs 30.0%, p = 0.560). The 1 year, 2 years, and 3 years progression-free survival (PFS）and overall survival (OS) in NACRT and ACT groups were 80.0% vs 56.7%, 73.3% vs 46.7%, 60.0% vs 33.3%, and 86.7% vs 80.0%, 76.7% vs 66.7%, 63.3% vs 50.0%, respectively. Patients in NACRT group showed a significantly higher R0 resection rate (84.6% vs 56.7%, p = 0.029),lower loco-regional recurrence rate (36.7% vs 11.5%, p = 0.039), longer PFS (p = 0.019) and freedom from locoregional progression(FFLP) (p = 0.004) than patients in ACT group, while there was no difference in OS (p = 0.215) and in toxicity incidence (p > 0.05). Conclusions: NACRT combined with postoperative adjuvant XELOX chemotherapy can improve R0 resection rate, reduce loco-regional recurrence, prolong PFS and FFLP without increasing the incidence of postoperative complications in patients with LAGC. Advances in knowledge: Compared with postoperative adjuvant chemotherapy, locally advanced gastric cancer patients may benefit from neoadjuvant chemoradiotherapy, and toxicity associated with chemoradiotherapy was tolerant and manageable.

This study aimed to investigate risk factors associated with oxaliplatin hypersensitivity reactions in cancer patients through a meta-analysis. A comprehensive retrieve of Chinese databases China National Knowledge Infrastructure, Wanfang Data, VIP Database and English databases PubMed, ScienceDirect, Embase and Cochrane library was conducted. The studies that meet the requirements for meta-analysis according to inclusion and exclusion criteria were screened and assessed for eligibility. Odds ratio (OR) / Weighted mean difference (WMD) and 95% confidence intervals (95% CIs) or calculable dichotomous and continuous raw data were extracted to perform meta-analysis using random effect model or fixed effect model on the basis of heterogeneity between studies through Review Manager 5.4 software. A total of 14 cross-sectional studies and 3367 cancer patients were included. Meta-analysis results showed that platinum exposure history (OR value 3.13, 95% CI 2.19–4.48, heterogeneity P = 0.26), allergy history (OR value 1.76, 95% CI 1.09–2.85, heterogeneity P = 0.61), platinum free interval (OR value 3.75, 95% CI 2.00–7.06, heterogeneity P = 0.83), dexamethasone premedication dose (OR value 0.28, 95% CI 0.13–0.58, heterogeneity P = 0.21) were significantly correlated to oxaliplatin hypersensitivity reactions. Gender, age, metastasis, combination with bevacizumab, XELOX regimen and cancer types were detected to have no statistically significant effect on oxaliplatin hypersensitivity reactions. Platinum exposure history, allergy history and long platinum-free interval are risk factors of oxaliplatin hypersensitivity reactions. High dexamethasone premedication dose is a protective factor of oxaliplatin hypersensitivity reactions.

ObjectiveTo compare the efficacy of adjuvant chemotherapy with six or eight cycles of S-1 plus oxaliplatin (SOX) or Capecitabine plus oxaliplatin (XELOX) after D2 resection of GC.Design and participantsWe collected 470 cases of patients with TNM stage II and III GC who underwent D2 gastrectomy in the Harbin Medical University Cancer Hospital from January 2007 to December 2017 and received six or eight cycles of SOX or XELOX regimen. This study was designed to evaluate the prognosis of patients receiving six or eight cycles of SOX or XELOX chemotherapy and identify the appropriate number of chemotherapy cycles.ResultsAmong the 470 study participants [340 (72.3%) males; median age, 50 years (range, 24-76 years)], 355 and 115 received XELOX or SOX regimen chemotherapy, respectively. The number of 152 patients included in this study who received 6 and 8 cycles of chemotherapy in stage II and stage III without considering chemotherapy regimens were 125 and 27. The median DFS was, respectively, 14.9 months and 26.8 months (P = 0.08), the median OS was, respectively, 30.2 months and 30.8 months (P = 0.5), the difference was not statistically significant. Comprehensive survival analysis of XELOX and SOX group showed no significant difference for DFS (P = 0.29) and OS (P = 0.61). The total number of stage III GC patients who received six and eight cycles of chemotherapy was 92 and 19, respectively. The median DFS of patients who received six and eight cycles of chemotherapy was 14.6 and 23.2 months (P = 0.3), respectively. The median OS of patients who received six and eight cycles of chemotherapy was 26 and 30.6 months (P = 0.9), respectively. Comprehensive analysis of DFS (P=0.73) and OS (P=0.6) shows no difference between the XELOX group SOX groups. Subgroup analysis revealed significant differences in the gender (P = 0.05) and histological classification (P < 0.05) distribution.ConclusionRegardless of the XELOX regimen or the SOX regimen, similar survival benefits are observed in patients receiving six or eight chemotherapy cycles irrespective of the regimen used. The XELOX and SOX regimens are well tolerated in patients undergoing D2 resection of GC.

Background: It’s still controversial whether triplet is better than doublet regimen in first-line treatment of advanced gastric cancer (AGC). We aimed to compare the efficacy and safety of new generation doublet regimen XELOX and EOX triplet regimen. Methods: EXELOX was an open-label, multicenter, randomized phase III trial that enrolled 448 previously untreated patients with AGC. Patients were randomly assigned to receive XELOX or EOX regimen. The primary endpoint was noninferiority in progression-free survival (PFS) for XELOX as compared with EOX on an intention-to-treat basis. The second endpoints included overall survival(OS), objective response rate(ORR), safety, and quality of life (QoL). This study is registered with ClinicalTrials.gov, number NCT02395640. Findings: Between Apr 10, 2015 and Aug 20,2020, 448 AGC patients were randomized to receive XELOX (n=222) or EOX (n=226). In ITT basis, the median PFS was 5.0 months (95%CI 4.5-6.0) in XELOX group and 5.5 months (95%CI 5.0-6.0) in EOX group (HR 0.989, 95%CI 0.812-1.203; Pnon-inferiority =0.0032). There was no significant difference in median OS (12.0 vs. 12.0 months, HR 1.097, p =0.384), or ORR(37.4% vs. 45.1%, p =0.291) between two groups. In patients with poor differentiated adenocarcinoma and liver metastasis, EOX arm had significant longer mOS(p=0.021) and trend of longer mPFS(p=0.073) than XELOX arm. The incidence of grade 3/4 adverse events (AEs) was 42.2% (90/213) in XELOX group and 72.5% (156/215) in EOX group (p=0.001). The Global Health/QoL score were significantly higher in XELOX group than EOX group during chemotherapy. Interpretation: This is the first noninferiority trial demonstrating that doublet is as effective as triplet regimen generally, with a better safety profile and QoL as first-line treatment for AGC patients; but triplet regimen might have effects advantage in selected subsets, providing solid evidence for guideline update and guidance for future clinical trial design. Trial Registration: This study is registered with ClinicalTrials.gov, number NCT02395640 . Funding: This study was supported by The National Key Research and Development Program of China [grant no. 2017YFC1308900]; The clinical research and cultivation project of shanghai Shenkang hospital development center [grant no. SHDC12017X01] and Sun Yat-sen University Xie Tong Chuang Xin Program [grant no. ZLYXXTCX201504]. Declaration of Interest: None to declare. Ethical Approval: The trial protocol was approved by the local institutional review board and ethics committee.

Hyperammonemic encephalopathy represents a rare adverse effect of several chemotherapeutic agents, occurring in about 0.7% of patients treated with fluoropyrimidines, and it is independent from dihydropyrimidine dehydrogenase deficiency. Instead, its physiopathology is linked to the inhibition of Krebs cycle by fluoroacetate, leading to decreased ATP production, and to the inhibition of the urea cycle. Oxaliplatin seems to induce hyperammonemic encephalopathy in a similar way, acting on mitochondria. Here, we report the intriguing case of acute hyperammonemic encephalopathy in a 65-year-old patient with preserved liver function, who was treated with oxaliplatin and capecitabine for a metastatic, G1, atypical lung carcinoid. We reviewed the literature and found very few reports of oxaliplatin or capecitabineinduced hyperammonemic encephalopathy. Out of five cases of capecitabine-related hyperammonemic encephalopathy analyzed (four plus our case), median time to hyperammonemic encephalopathy onset was 6 days, with median serum ammonia levels of 213 μmol/L. Oxaliplatin-related hyperammonemic encephalopathy analyzed cases were three (two plus ours), with a median time to hyperammonemic encephalopathy of 11 days and median serum ammonia levels of 167 μmol/L. Identified predisposing factors for chemotherapy-induced hyperammonemia, such as dehydration, liver and renal impairment, infections, and sarcopenia were absent in our case. We hypothesize that the combination of a platinum-derivative and a fluoropyrimidine multiplies the risk of hyperammonemic encephalopathy, even in the absence of predisposing factors nor impaired liver function. We therefore suggest to always consider the risk of hyperammonemia when starting fluoropyrimidinesbased chemotherapy, especially combined with platinumderivatives, and to timely investigate neurologic symptoms monitoring ammonia serum levels. Anti-Cancer Drugs 31: 1103-1105.

Purpose We aimed to identify potential clinical parameters that can be easily obtained by a pre-treatment clinicopathological evaluation and whole blood test to estimate the development of oxaliplatin-induced peripheral neuropathy (OIPN). Methods This study was conducted retrospectively. For the FOLFOX regimen, patients received oxaliplatin, 85 mg/m2 , every 2 weeks for 12 courses, and with the XELOX regimen, oxaliplatin was 130 mg/m2 , every 3 weeks for 6–8 courses. The incidence and degree of neuropathy (NCI-CTCAE v.3) were recorded. Results A total of 186 patients were included in the study. There were 108 (58%) patients in the grade 0–1 (G0–G1) neuropathy group (mean age 50.5 ± 11.5; 63% men), and 78 (42%) patients in the grade 2–3 (G2–G3) neuropathy group (mean age 58.0 ± 10.8; 46.2% men). The relationship between G2–G3 OIPN development and age (p < 0.001), gender (p = 0.02), and ECOG performance status (p = 0.007) was statistically significant. In the G2–G3 neuropathy group, serum gamma-glutamyl transferase (GGT) (p < 0.001) and glucose (p = 0.007) levels were higher, whereas vitamin D (p < 0.001), hemoglobin (Hgb) (p < 0.001), serum albumin (p = 0.001), and serum magnesium (p = 0.035) levels were lower compared with the G0–G1 neuropathy group. G2–G3 neuropathy was observed in 88% of patients with mucinous carcinoma pathologic type (p < 0.001). Conclusion This study demonstrated that age, histopathologic type, albumin, GGT, glucose, vitamin D, and Hgb levels were the effective factors in prediction of the development of OIPN. In addition, GGT, vitamin D, and Hgb levels were the most effective factor to predict development of OIPN.

Objective: The aim of the present Bayesian network meta-analysis (NMA) was to explore the comparative effectiveness and safeaty of different Chinese Medicine injections (CMIs) combined with the XELOX regimen versus XELOX alone for colorectal cancer (CRC). Methods: A comprehensive search for randomized controlled trials (RCTs) was performed with regard to different CMIs for the treatment of CRC in several electronic databases up to April 2022. The quality assessment of the included RCTs was conducted according to the Cochrane risk of bias tool. Standard pair-wise and Bayesian NMA were designed to comparethe effectiveness and safety of different CMIs combined with the XELOX regimen by utilizing R 4.0.3 software and Stata 15.1 software simultaneously. Results: Initially, a total of 4296 citations were retrieved through comprehensive searching, and 32 eligible articles involving 2847 participants and 11 CMIs were ultimately included. CMIs combined with XELOX were superior to the XELOX regimen alone, and a total of ten Observation Indicators were included in the study, with the following results. Among all the injections, Shengmaiyin, Shenmai, and Kanglaite combined with the XELOX regimen were the three CMIs with the highest clinical efficiency. The top three in terms of improving CD3 + values were Shengmaiyin, Shenqifuzheng, and Cinobufacini injections. Shenqifuzheng, Shengmaiyin, and BruceaJavanica oil injections combined with the XELOX regimen performed best at raising CD4 + values. Kanglaite, Cinobufacini, and Matrine injections combined with the XELOX regimen performed best in improving CD4+/CD8+ rates. The top three in terms of improving performance status were Xiaoaiping, Shenmai, and Kanglaite injections. Cinobufacini and Brucea Javanica oil injections combined with the XELOX regimen performed best at raising CD8 + values. Shenqifuzheng, Kangai, and Matrine injections combined with the XELOX regimen performed best in improving Gastrointestinal reactions.The top threein terms of improving Leukopenia were Shenqifuzheng, Compound Kushen and Kanglaite injections. The top three in terms of improving Platelet decline were Compound Kushen, Cinobufacini and Shenqifuzheng injections. Additionally, those that were best at improving nausea and vomitting were Cinobufacini, Compound Kushen and Aidi injections. Conclusion: The results of the analysis demonstrated thatShengmaiyin, Kanglaite, and Cinobufacini injections and the XELOX regimen were associated with morepreferable and beneficial outcomes than other CMI groups. Nevertheless, additional results from multicenter trials and high-quality studies will bevital to support our findings. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display&#95;record.php?RecordID=326097, CRD42022326097., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Zhang and Hu.)

Yong-Hong Hu,1,2,* Jia-Wang Wei,1–3,* Hui Chang,1,2,* Wei-Wei Xiao,1,2 Jun-Zhong Lin,1,4 Mu-Yan Cai,1,5 Pei-Qiang Cai,1,6 Ling-Heng Kong,1,4 Gong Chen,1,4 Zhi-Zhong Pan,1,4 Zhi-Fan Zeng,1,2 Pei-Rong Ding,1,4 Yuan-Hong Gao1,2 1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People’s Republic of China; 2Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, People’s Republic of China; 3Departments of Oncology, Ganzhou People’s Hospital, Ganzhou, Jiangxi, People’s Republic of China; 4Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People’s Republic of China; 5Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, People’s Republic of China; 6Department of Medical Imaging and Interventional Radiology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, People’s Republic of China *These authors contributed equally to this work Background: In a Phase II clinical trial, we reported the effectiveness and safety of a sandwich neoadjuvant treatment based on a modified oxaliplatin plus capecitabine (XELOX) regimen for locally advanced rectal cancer (LARC). The pathologic complete response (pCR) rate was 42.2%, and no patient presented Grade 4 acute toxicities. This study was performed to evaluate whether the high pCR rate could translate into an improved long-term survival benefit by analyzing the 5-year follow-up results of the trial.Methods: Fifty-one patients with LARC were initially enrolled in the trial. Of these, 2 cases were eliminated due to distant metastasis before treatment. In addition, 4 cases were eliminated for refusing surgery after neoadjuvant chemoradiotherapy (NACRT). Finally, a total of 45 patients were treated with the sandwich NACRT plus total mesorectal excision. We followed up these patients and calculated their overall survival (OS) and disease-free survival (DFS) through a Kaplan–Meier approach. A log-rank test and multivariate survival analysis based on a Cox proportional hazard model were performed to explore the risk factors influencing distant metastasis.Results: The median follow-up time was 60.8 months, and among the 45 patients analyzed, 1 (2.2%) patient suffered local recurrence, and 9 (20.0%) suffered distant metastasis. The 3-year OS and DFS were 95.6% and 84.4%, respectively. In addition, the 5-year OS and DFS were 91.1% and 80.0%, respectively. In the multivariate analysis, postsurgical pathological N stage and carbohydrate antigen 19–9 before treatment maintained statistical significance on distant metastasis.Conclusions: The sandwich NACRT with XELOX regimen might reduce distant metastasis and improve the survival of LARC patients. However, long-term benefits should be verified through further Phase III clinical trials. Keywords: rectal neoplasms, neoadjuvant chemoradiotherapy, locally advanced, neoadjuvant therapy, prognosis

Purpose: This study aimed at investigating the long-term outcomes of oxaliplatin and capecitabine (XELOX) administered concurrently with preoperative radiation and extended to the resting period in patients with high-risk locally advanced rectal cancer (LARC). Methods: From January 2010 to December 2013, 45 patients were recruited. Study treatment consisted two cycles of XELOX regimen concomitant with preoperative radiation and then followed by an additional cycle of XELOX regimen between completion of neoadjuvant radiotherapy and surgery. Disease-free survival (DFS) time and overall survival (OS) time were analyzed. Results: The median follow-up was 51 months. Twelve (26.7%) patients developed local recurrence or distant metastasis, including 10 (22.2%) patients developing distant metastasis only, 1 (2.2%) patient local recurrence only, and 1 (2.2%) patient both local recurrence and distant metastasis. The estimated 3-year DFS and OS was 75.5% (95% CI, 63.0%-88.0%) and 88.6% (95% CI, 98.0%-79.2%), respectively. Receiving adjuvant chemotherapy was a significant predictor for DFS, with hazard ratio 0.24 (95% CI: 0.08-0.74). Conclusion: This intensified strategy with oxaliplatin and capecitabine (XELOX) administered concomitantly with neoadjuvant radiotherapy and then extended to the resting period in high-risk LARC patients is efficient. The long-term outcome is promising. Further study of this strategy is warranted.

PURPOSE/OBJECTIVE(S): to investigate the clinical and dose-volume factors of radiation-induced liver disease (RILD) during preoperative chemoradiotherapy for local advanced gastric adenocarcinoma, and provide a reference for optimization of the radiation plans. MATERIALS/METHODS We retrospectively observed the clinical characteristics as well as dose-volume factors in a cohort of 190 patients with local advanced gastric adenocarcinoma in our hospital, including gender, age, treatment group, clinical TNM classification, primary tumor site, hepatitis, body mass index (BMI), alanine aminotransferase (ALT), alkaline phosphatase (ALP), serum albumin (ALB), total bilirubin (TBIL), activated partial thromboplastin time (APTT) from June 2013 to November 2020, based on an ongoing multicentric randomized phase III clinical trial (NCT01815853). There are 98 patients receiving chemotherapy (ChT, 3 cycles of XELOX regimen), and 99 patients receiving chemoradiation therapy (CRT, 1 cycle of induced XELOX regimen and 4500cGy/25f IMRT radiotherapy plus concurrent extenuated 2 cycles of XELOX regimen) before radical gastrectomy. The evaluation of RILD was performed based on clinical symptoms, Child-Pugh score system, Common Terminology Criteria of Adverse Event (CTCAE) 5.0 during preoperative treatment. ROC curves were used for appropriate cut-off values. Univariant and multivariant analysis were performed in dose-volume factors to find significant variables. RESULTS In all of the patients, the incidence rate of RILD is 7.3%. With aid of supportive and symptom-eliminating treatments, all but one patient completed the assigned preoperative treatment. The RILD rate in the CRT group was higher than in ChT group (12.1% vs 2.2%, P = 0.009). As for the patients in CRT group, there were significant discrepancies in V3.5Gy (P = 0.017), V5Gy (P = 0.018), V10Gy (P = 0.033), V15Gy (P = 0.019), and borderline significance in the maximum dose (Dmax, P = 0.078) of liver between RILD patients and non-RILD patients in CRT group. Subsequent analysis showed that patients with the liver V3.5Gy (%) > 99.975%, liver V15Gy (%) > 66.470% had higher risk of RILD (OR: 5.797, P = 0.016; OR: 6.601, P = 0.023; respectively). However, V5Gy and V10Gy couldn't be considered as independent factors based on multivariant analysis (P = 0.757, P = 0.219, respectively), and the value of Dmax as independent prognostic factor was borderline significant (P = 0.050). There were no significant association between RILD and other clinical characteristics. CONCLUSION Compared to chemotherapy, chemoradiation can increase the risk of RILD during preoperative treatment, but it's safe with regularly monitoring and appropriate treatment. Under the condition of the present liver-dose limitation, reduction of liver radiated volume in low dose (

Introduction. A comparison of the cost of an alternative treatment regimen is the basis of the rationalisation and cost effectiveness of cancer therapy. The aim of the study was to compare two alternative treatment regimens for colorectal cancer in the III and IV advancement stage (FOLFOX4 and XELOX). Material and methods. A cost-effectiveness analysis was carried out on the basis of data collected retrospectively; considering 100 patients treated at the Oncology Centre in Bydgoszcz. A measure of the effectiveness of the therapy was the total survival time of patients. Data on the average survival time of patients has been obtained from clinical trials. Results. The total cost of treatment per patient was 33 879.13 PLN in FOLFOX4. In XELOX the average cost per patient was 20 023.96 PLN. The endpoint, defined as the average survival time of patients treated with the FOLFOX4 scheme amounted to 27.25 months. In the case of the use of the XELOX regimen, the average survival time was 23.65 months. Incremental costs for additional units as a result of using the more expensive treatment regimen were estimated as 46 183.47 PLN. Conclusions. The comparison of the two treatment regimens for colorectal cancer in stage III and IV, which were used in the Oncology Centre in Bydgoszcz, showed that the more expensive but more efficient treatment was FOLFOX4.

Xiao Ai Ping injection (XAPI), extracted from the Chinese herbal medicine Marsdenia tenacissima, is widely used in the adjuvant treatment of tumors in China. The present study aimed to evaluate the efficacy and safety of XAPI combined with chemotherapy for treating patients with advanced gastric cancer. Seven databases were searched for relevant studies published up to October 1, 2018, and Review Manager 5.3 software and Stata 12.0 software were used for meta-analysis. Fourteen studies, representing 1097 enrolled patients, were included in our analysis. Compared with chemotherapy alone, combination treatment with XAPI and the XELOX regimen (capecitabine plus oxaliplatin) was found to improve the objective response rate (ORR) [RR=1.36; 95%CI (1.10, 1.70); P=0.006], disease control rate (DCR) [RR=1.15; 95% CI (1.04, 1.28); P=0.010], and Karnofsky Performance Status (KPS) improvement rate [RR=1.51; 95%CI (1.14, 2.00); P=0.004] and to reduce the incidence of leukopenia [RR=0.68; 95%CI (0.55,0.84); P=0.0005], liver damage [RR=0.59; 95% CI (0.37, 0.92); P=0.02], renal impairment [RR=0.39; 95% CI (0.18, 0.85); P=0.02], and hand-foot syndrome [RR=0.56; 95%CI (0.35,0.90); P=0.02]. However, median progression-free survival (PFS), 1-year survival rate, and median overall survival (OS) were not extended by XAPI plus XELOX. Combination treatment with XAPI and the SOX regimen (tegafur plus oxaliplatin) did not improve ORR or DCR, but it did enhance the KPS improvement rate [RR=1.73; 95%CI (1.23,2.43); P=0.002] and reduce the incidence of nausea and vomiting [RR=0.66; 95% CI (0.50, 0.88); P=0.004]. XAPI in combination with the FOLFOX regimen (fluorouracil/calcium folinate/oxaliplatin) enhanced only the KPS improvement rate [RR=1.68; 95%CI (1.18,2.39); P=0.004] and had no significant effect on ORR or DCR or the incidence of adverse events. A single study reported that XAPI combined with the CPT-11 regimen (irinotecan) was superior to chemotherapy alone with respect to DCR and also reduced the incidence of leukopenia, liver damage, and hand-foot syndrome during chemotherapy, while prolonging PFS. Finally, one study reported that XAPI combined with the TP regimen (palitaxel plus cisplatin) improved ORR and KPS improvement rate to a greater extent than TP alone. Although the present review has some limitations, the findings suggest that XAPI combined with chemotherapy may represent a beneficial treatment strategy, particularly the combination of XAPI and XELOX.

4014 Background: At present, there is no standard chemotherapy regimen for advanced gastric cancer (AGC), and there is no consensus whether the three-drug combination is better than two-drug combination in first-line treatment. Both of XELOX regimen and EOX regimen are widely recommended as firs-line chemotherapy regimens for AGC. In this EXELOX trial, we aimed to compare the efficacy and safety of EOX and XELOX regimens. Methods: EXELOX is an open-label, multicenter, prospective, randomized phase III trial that enrolled 448 previously untreated patients with histologically confirmed advanced gastric adenocarcinoma from 7 hospitals in China. Patients were randomly assigned (1:1) to receive XELOX regimen (oxaliplatin 130mg/m2 d1; xeloda 1000mg/m2 bid d1-14) or EOX regimen (epirubicin 50mg/m2 d1; oxaliplatin 130mg/m2 d1; xeloda 1000mg/m2 bid d1-14) in this study. Treatment was repeated every 3 weeks until disease progression, intolerable toxicity, patient death, withdrawal of informed consent, or up to eight cycles, followed by xeloda single-agent maintenance. We stratified randomization by Eastern Cooperative Oncology Group status, extent of disease(locally advanced/metastatic) and clinical trial center. Patients and clinicians were not masked to the allocated treatment. The primary endpoint was progression-free survival (PFS) on an intention-to-treat basis with a non-inferiority upper margin of 1.3 for the hazard ratio (HR). The clinical trial was a non-inferiority study that was registered with ClinicalTrials.gov, Number NCT02395640. The study is ongoing, but no longer recruit new participants. Results: Between Apr 10,2015 and Aug 20,2020, a total of 448 AGC patients were randomized to receive XELOX (n = 222) or EOX (n = 226). In ITT basis, the median PFS was 5.0 months (95%CI 4.5-6.0) in XELOX group and 5.5 months (95%CI 5.0-6.0) in EOX group (HR 0.989, 95%CI 0.812-1.203; Pnon-inferiority= 0.0032). In Per-protocol population (n = 428), the median PFS was 5.0 months (95%CI 5.0-6.0) in XELOX group and 5.5 months (95%CI 5.0-6.0) in EOX group (HR 0.983, 95%CI 0.807-1.198; Pnon-inferiority= 0.0028). The incidence of grade 3-4 adverse events (AEs) was 42.2% (90/213) in XELOX group and 72.5(156/215) in EOX group ( p= 0.001). The most common grade 3-4 AEs were neutropenia (affecting 13.1% (28/213) in XELOX group and 48.4%(104/215) in EOX group ( p= 0.000). The incidence of chemotherapy dose reduction was 35% (75/213) in XELOX group and 55% (120/215) in EOX group( p= 0.009). One treatment-related death (lung infection) was observed in EOX group, and none in XELOX group. Conclusions: XELOX regimen is noninferior to EOX regimen in PFS with a better safety profile as first-line treatment for AGC patients, therefore XELOX is a more favorable choice and might be one of the standard first-line chemotherapy regimens. Clinical trial information: NCT02395640.

70 Background: The combination of anti-VEGF or anti-EGFR targeted drugs with chemotherapy is considered as the standard first-line therapy for metastatic colorectal cancer (mCRC), and maintenance treatment is proven to be a promising and controversial therapeutic strategy which is mainly involved bevacizumab or capecitabine. However, studies regarding the maintenance strategies based on antiangiogenic TKIs are limited currently. Anlotinib is a novel oral multi-target TKI which can inhibit both tumor angiogenesis and tumor cell proliferation simultaneously. Previous studies indicated that anlotinib demonstrated clinical benefits for patients with mCRC. This study aimed to evaluate the efficacy and safety of anlotinib plus XELOX as first-line treatment followed by anlotinib maintenance therapy for mCRC. Methods: ALTER-C-001 trial was an open label, single-arm, multicenter phase II study. A calculated sample size of 53 patients with previously untreated mCRC, ranging from 18-75 years old and an ECOG performance status ≤ 1 were planned to recruit. Eligible patients were treated with capecitabine (1000 mg/m2, po, d1-14, q3w) and oxaliplatin (130 mg/m2, iv, d1, q3w) plus anlotinib (10mg, po, d1~14, q3w) for 6 cycles followed by maintenance therapy of anlotinib (12mg, po, d1~14, q3w) until disease progression or intolerable adverse events (AEs). The primary endpoint was progression-free survival (PFS). Secondary endpoints were ORR, DCR, DOR and safety. Results: From January 2020 to September 2020, a total of 9 patients were enrolled, 6 patients were available for efficacy assessment. In best overall response assessment (all confirmed), there were 66.7% PR (4/6), 16.7% SD (1/6) and 16.7% PD (1/6). The preliminary ORR and DCR of the 6 patients was 66.7% (95% CI, 22.3-95.7%) and 83.3% (95% CI, 35.9-99.6%), respectively. The median PFS was not reached. Most treatment-related adverse events (TRAEs) were grade 1-2. Grade 3 or above TRAEs were as follows: hypertriglyceridemia (33.3%), hypertension (16.7%), neutropenia (16.7%) and lipase elevated (16.7%). No grade 5 AEs were observed. Conclusions: The preliminary results indicated that anlotinib plus XELOX regimen followed by anlotinib monotherapy as first-line treatment exhibited antitumor efficacy and manageable toxicity for patients with mCRC. The study is still ongoing and the data will be updated subsequently. Clinical trial information: ChiCTR1900028417.

Background The gut microbiome changes are related to the colorectal cancer (CRC). Chemotherapy is one of the main treatment methods for CRC. Purpose To explore the effect of chemotherapy on the gut bacteria and fungi in CRC. Methods Total of 11 advanced CRC patients treated with the FOLFIRI regimen, 15 postoperative CRC patients treated with the XELOX regimen, and corresponding CRC patients without surgery and chemotherapy were recruited. The 16S ribosomal RNA and ITS sequences were sequenced, and bioinformatics analysis was executed to screen for the distinctive gut microbiome. Results The abundances of Veillonella, Humicola, Tremellomycetes and Malassezia were increased in postoperative CRC patients treated with the XELOX regimen. The abundances of Faecalibacterium, Clostridiales, phascolarctobacterium, Humicola and Rhodotorula were decreased, and the abundances of Candida, Magnusiomyces, Tremellomycetes, Dipodascaceae, Saccharomycetales, Malassezia and Lentinula were increased in advanced CRC patients treated with the FOLFIRI regimen. The abundances of Humicola, Rhodotorula, and Magnusiomyces were decreased, and the abundances of Candida, Tremellomycetes, Dipodascaceae, Saccharomycetales, Malassezia and Lentinula were increased in advanced CRC patients treated with the FOLFIRI regimen combined with cetuximab compared with those treated with the FOLFIRI regimen alone. Conclusions The community structure of gut bacteria and fungi changes in chemotherapy on CRCs.

Gastric adenocarcinoma concurrent with metastatic neuroendocrine cancer (NEC) is rare. In the present case report, a 39-year-old male was first pathologically diagnosed by gastric endoscopy as having a highly differentiated adenocarcinoma. Next, positron emission tomography-computed tomography examination and bone marrow biopsy confirmed extensive metastasis. Subsequently, the patient underwent 6 cycles of immunotherapy (nivolumab, 160 mg) and 5 cycles of chemotherapy based on the XELOX regimen (oxaliplatin + capecitabine). Following this, the patient received the final cycles of nivolumab and XELOX; however, the patient then succumbed. Further biopsy of the metastatic collarbone lymph nodes indicated NEC. Overall, the progression-free survival was ~3.5 months, and overall survival (OS) was ~6 months. The case presented the possibility of concurrent gastric adenocarcinoma and NEC in the clinic. In addition, the efficacy of a combined regimen such as immunotherapy and chemotherapy for such disorders still requires further validation in the future.

Background: The optimal Chinese herbal injections (CHIs) combined with XELOX regimen for patients with gastric cancer remains elusive. The aim of our network meta-analysis (NMA) is to explore the best options among different CHIs for gastric cancer. Methods: PubMed, Embase, the Cochrane Library, the China National Knowledge Infrastructure Database (CNKI), Wan-fang Database, Cqvip Database (VIP), China Biology Medicine disc (CBMdisc) were searched to identify RCTs which focused on CHIs against gastric cancer. The quality assessment of included randomized controlled trials (RCTs) was conducted by the Cochrane risk of bias tool. Standard pair-wise and Bayesian NMAs were performed to compare the efficacy and safety of different CHIs combined with the XELOX regimen via Stata 13.0 and WinBUGS1.4 software. Results: A total of 2316 records were searched, the network of evidence included 26 eligible RCTs involving 13 types of CHIs and 2154 patients. The results suggested that Shenqifuzheng+ XELOX, Huachansu+ XELOX, Kangai+ XELOX, Javanica oil emulsion+ XELOX, Aidi injection+ XELOX might be the optimal treatment for gastric cancer in improving the performance status than using XELOX regimen single, with odds ratios (OR) and 95% confidence intervals (CIs) of 2.74 (1.24, 6.17), 8.27 (1.74, 42.43), 4.28 (1.80, 10.48), 5.14 (1.87, 16.28), 0.20 (0.090, 0.44). At the aspects of ADRs (adverse reactions), Compound Kushen+ XELOX, Lentinan+ XELOX, Xiaoaiping injection+ XELOX could obviously relieve leukopenia than only receiving XELOX regimen, and their ORs and 95% CIs were 5.62 (1.41, 36.24), 8.16 (2.25, 29.43), 5.69 (1.85, 15.77). Furthermore, Disodium cantharidinate and vitamin B6+ XELOX, Shenqifuzheng+ XELOX, Kangai+ XELOX, Lentinan+ XELOX could obviously relieve the nausea and vomiting than receiving the XELOX regimen alone, with ORs and 95% CIs of 5.29 (1.30, 23.96), 2.50 (1.16, 5.26), 2.42 (1.06, 5.63), 9.04 (3.24, 26.73). Nevertheless, CHIs combined with XELOX regimen did not confer higher better clinical effectiveness rate over receiving XELOX regimen alone, with nonstatistically significant between-group differences. Conclusions: As the available evidence suggested that CHIs combined with XELOX regimen could provide treatment benefits for patients with gastric cancer. Among 13 types of CHIs, Javanica oil emulsion and Compound Kushen injection is the optimal treatment in improving the clinical effectiveness rate and performance status, and Lentinan injection was superior in relieving ADRs.

Oxaliplatin is part of pancreatic cancer therapy in the FOLFIRINOX or GEMOX/XELOX regimen. DNA damage repair is one of the factors responsible for oxaliplatin resistance that eventually develops in this cancer. Triptolide/Minnelide has been shown to be effective against pancreatic cancer in preclinical trials. In this study, we evaluated the efficacy of combination of triptolide and oxaliplatin against pancreatic cancer. Highly aggressive pancreatic cancer cells (MIA PaCa-2 and PANC-1) were treated with oxaliplatin (0–10 μM), low-dose triptolide (50 nM), or a combination of both for 24–48 h. Cell viability, apoptosis, and DNA damage were evaluated by appropriate methods. Nucleotide excision repair pathway components were quantitated using qPCR and Western blot. Combination of low doses of Minnelide and oxaliplatin was tested in an orthotopic murine model of pancreatic cancer. Proliferation of pancreatic cancer cells was markedly inhibited by combination treatment. Triptolide potentiated apoptotic cell death induced by oxaliplatin and sensitized cancer cells towards oxaliplatin-induced DNA damage by suppressing the oxaliplatin-induced DNA damage repair pathway. Combination of low doses of Minnelide and oxaliplatin inhibited tumor progression by inducing significant apoptotic cell death in these tumors. Combination of low doses of Minnelide and oxaliplatin has immense potential to emerge as a novel therapeutic strategy against pancreatic cancer.

The XELOX regimen (capecitabine plus oxaliplatin) has been demonstrated as first-line chemotherapy for gastric cancer in China. However, the efficacy of XELOX varies in individuals. Some evidences indicate that the variable efficacy might be related to the distinct immune status not only in the tumor site but also in the systemic immune system, and further investigation is required. In this study, we collected 32 PBMC samples from 16 XELOX-treated patients with gastric cancer and analyzed the patterns of immune cells. At the end point, the proportion of CD24(hi)CD27(+)CD19(+) B cells in patients without progression revealed a significant decrease compared with that in patients with progression, but not other immune cells, such as T cells and NK cells. Furthermore, CD19(+) B cells were more sensitive to capecitabine plus oxaliplatin stimulation in vitro than other immune cells, displaying higher frequency of apoptosis in a dose-dependent way. Thus, our results suggested that the outcomes of XELOX chemotherapy were inversely correlated with peripheral B cell subsets, which might provide a more convenient method to predict gastric cancer progression of XELOX-treated patients.

Objective: This study was conducted to investigate the efficacy and safety of using a concurrent neoadjuvant chemoradiotherapy (a XELOX regimen) to treat adenocarcinoma of the gastroesophageal junction. Methods: Seventy-six patients having resectable adenocarcinoma at the gastroesophageal junction (T3/4, N+, M0) were recruited to participate and randomly assigned to either a chemoradiotherapy group or a surgery group. Patients in the chemoradiotherapy group were orally given capecitabine (1,000 mg/m2, twice daily for 14 days, days 1–14) and intravenous oxaliplatin (130 mg/m2 on day 1) for 2 cycles. Radiotherapy was performed with a total of 45 Gy administered in 25 sessions for 5 weeks. Patients in the surgery group received only surgical intervention. Results: In the concurrent chemoradiotherapy group, the overall response rate was 55.6% (20/36), tumor control rate was 100% and a pathological complete response was achieved in 16.7% (6/36). The entire chemoradiotherapy group had R0 resections as did 80% of the surgery group (32/40) (P < 0.05). In the concurrent chemoradiotherapy group, 6 patients developed grade 3 side effects. Treatment was either discontinued or the dose adjusted. Major hematological side effects in the chemoradiotherapy group included leukopenia, neutropenia, anemia and thrombocytopenia. Nonhematological side effects included nausea, vomiting and appetite loss. Chemoradiotherapy-related death was not observed. Conclusions: Concurrent neoadjuvant chemoradiotherapy administration increased the rate of R0 resection and demonstrated favorable safety in patients with Siewert II or III adenocarcinoma at the gastroesophageal junction. These results support the use of neoadjunctive chemoradiotherapy in the treatment of adenocarcinoma of the gastroesophageal junction.

Background The necessity for adjuvant chemotherapy (ACT) in locally advanced rectal cancer (LARC) patients who achieve pathological complete response (pCR) after pre-operative chemoradiotherapy (CRT) is still not identified. We aimed to investigate the therapeutic value of ACT in these patients. Methods Clinical data were retrospectively collected from 105 consecutive LARC patients who achieved pCR after pre-operative CRT and underwent radical tumor resection between December 2008 and April 2014 in a comprehensive cancer center. Perioperative chemotherapy (CT) was administered by combining oxaliplatin with capecitabine (XELOX regimen). Disease-free survival (DFS) and overall survival (OS) rates of patients with or without ACT were compared. Results Eighty-three (79.0%) patients received ACT and 22 (21.0%) did not. With a median follow-up of 49 months, the ACT group had a significantly higher 3-year DFS rate (92.8 vs 86.4%, p = 0.029) and 3-year OS rate (95.1 vs 86.1%, p = 0.026) than the non-ACT group. In multivariable analyses, the presence of ACT was an independent prognostic factor for DFS (hazard ratio [HR]: 0.271; 95% confidence interval (CI): 0.080–0.916; p = 0.036) but not for OS. This benefit was more obvious in patients younger than 60 years via subgroup analysis (adjusted HR: 0.106; 95% CI: 0.019–0.606; p = 0.012). Conclusions Oxaliplatin-containing ACT may confer survival benefits to patients with pCR, particularly younger patients. However, the routine use of ACT in patients with pCR needs further validation.

Background The aim of this study was to compare the efficacies of the XELOX and DOS regimens as preoperative chemotherapy in patients with locally advanced gastric cancer. Methods All cases of locally advanced gastric cancer treated with the XELOX or DOS regimen were reviewed retrospectively. Propensity score matching (PSM) was carried out to reduce selection bias based on age, gender, location, Lauren type, carcinoembryonic antigen level, clinical tumor stage, and clinical node stage. Results From January 2010 to December 2016, 248 patients were matched; 159 of them received the XELOX regimen and 89 the DOS regimen. The response rates in the XELOX and DOS groups were 34.5 and 38.1%, respectively (P = 0.823). After four cycles of chemotherapy, 111 patients (69.8%) in the XELOX group and 65 patients (73.0%) in the DOS group underwent radical surgery (P = 0.485). The median progression-free survival (33.0 months vs. 18.7 months, P = 0.0356) and the median overall survival (43.8 months vs. 29.1 months, P = 0.0003) were longer for patients who received the DOS regimen than for those who received the XELOX regimen. The occurrence of grade 3 to 4 toxicity was similar in the two groups. Conclusions For locally advanced gastric cancer patients, the DOS regimen showed more benefit than the XELOX regimen as preoperative chemotherapy, without any added toxicity effects.

Background DPYD has a key role in fluoropyrimidines metabolism. The relationship between enzyme activity and drug efficacy and toxicity has been widely studied, but the predictive value of the most accepted variants is still poor. Hence the search for new biomarkers is needed. Purpose To analyse if single nucleotide polymorphisms (SNPs) in the DPYD exon regions have an influence on disease free survival (DFS) in colorectal cancer patients treated with capecitabine based adjuvant chemotherapy. Material and methods The study design was observational, ambispective and multicentric. The study population included 138 adult patients with stages II and III colorectal cancer that received capecitabine based adjuvant chemotherapy. DNA was isolated from peripheral blood samples and seven polymorphisms (rs12119882, rs1801158, rs1801159, rs291592, rs291593, rs44221623, rs6668296) in the DPYD exon regions were genotyped through OpenArray technology. DFS was estimated by the Kaplan–Meier method. The relationship between polymorphisms and DFS was explored using the Cox regression model with tumour stage, treatment and hospital as co-variables. Results 76.8% of patients received capecitabine in combination with oxaliplatin (XELOX regimen), and the remaining 23.2% monotherapy. Median follow-up time was 30.1 months (range 7–171.9). At the cut-off date, 35 patients had relapsed (25.4%). Patients harbouring the DPYD rs291593 GG genotype had a worse DFS than those carriers of the GA/AA variants (HR 2.15; 95% CI 1.10–4.23; p=0.026). Patients with the TT homozygous genotype in DPYD rs1801159 also showed a trend to shorter DFS than heterozygous or homozygous carriers of the C allele when analysed by Kaplan–Meier (p=0.019). In multivariate analysis, differences remained in the limit of the statistical significance (HR 2.16; 95% CI 1.00–4.67; p=0.051). No statistically significant association was found between DFS and the other polymorphisms that were studied. Conclusion Genotyping of exonic genetic variants in DPYD are related to DFS after capecitabine based adjuvant chemotherapy in CRC patients and could be a successful approach to find new pharmacogenetic predictors of tumour relapse. However, more studies in larger cohorts with a longer follow-up are needed. No conflict of interest

Background: Gastric cancer is one of the most common malignant tumors worldwide, and the 2nd most common in China. The development of new agents for the treatment of advanced gastric cancer is stagnant. Immunotherapy which inhibits the programmed death 1 (PD-1)/ programmed death ligand 1 (PD-L1) interaction is becoming a new option for treatment of late-stage gastric cancer (GC). Several trials suggest patients with PD-L1 positive expression (Combined Positive Score: CPS ≥ 1) population, especially CPS ≥ 10 population, are most likely to benefit from anti-PD-1 antibody treatment. Emerging data show encouraging efficacy signals of anti-PD-1 antibody in combination with chemotherapy in GC. Sintilimab, a highly selective, fully human, anti-PD-1 monoclonal antibody, was approved for relapsed or refractory Hodgkin Lymphoma in China in 2008. Based on the efficacy signals and the safety profile from a phase 1b trial of sintilimab plus XELOX regimen (oxaliplatin and capecitabine) as first line treatment for unresectable advanced gastric and GEJ adenocarcinoma, we aim to verify the therapeutic potential of sintilimab in combination with chemotherapy in patients with advanced GC/gastroesophageal junction (GEJ) cancer . Methods: The ORIENT-16 study (NCT: 03745170) is a randomized, double-blind, multi-center, phase III trial conducted in China to evaluate the efficacy and safety of sintilimab or placebo in combination with XELOX as first-line treatment in subjects with recurrent unresectable locally advanced or metastatic GC or GEJ adenocarcinoma. The study will enroll 650 patients. Patients will be randomly assigned in a 1:1 ratio to receive sintilimab every 3 weeks plus XELOX (capecitabine, 1000mg/m2 orally twice daily for 14 days followed by 7 days off; oxaliplatin, 130mg/m2 intravenously on day1 every 3 weeks) or placebo plus XELOX for up to six cycles. Thereafter, the patients will receive maintenance therapy with sintilimab every 3 weeks plus capecitabine (1000mg/m2 orally twice daily for 14 days followed by 7 days off) or placebo plus capecitabine every 3 weeks. Sintilimab will be dosed according to the subject’s bodyweight ( < 60kg, 3mg/kg; ≥ 60kg, 200mg). Stratification factors are ECOG Performance status (0 or 1), liver metastasis (yes or no) and PD-L1 expression score in tumor cells and immune cells (DAKO 22C3: CPS < 10 or ≥ 10). Major eligibility criteria include age between 18 and 75 years; newly diagnosed, recurrent unresectable locally advanced or metastatic G or GEJ adenocarcinoma; at least one evaluable tumor lesion according to RECIST v1.1 criteria; and patients must have fresh tumor tissue or archival tumor tissue for PD-L1 assessment from within 6 months of entrance. Patients with known HER2 positive G or GEJ cancer are excluded. Treatment will be discontinued for disease progression, unacceptable toxicity, patient / physician decision to withdraw or after 24-months of treatment. The primary endpoint is median overall survival assessed in both entire population and in PD-L1 positive (CPS ≥ 10) population of patients. Secondary endpoints include progression free survival, objective response rate, disease control rate,duration of response and safety. Recruitment is currently ongoing in multiple sites in China. Citation Format: Jianming Xu, Yongshuai Jin, Ying Liu, Hui Zhou, Yan Wang. ORIENT-16: Sintilimab plus XELOX vs placebo plus XELOX as 1st line treatment for unresectable advanced gastric and GEJ adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT213.

Background: Inflammation plays an important role in tumor progression. Predicting survival is remarkably difficult in patients with gastric cancer receiving neoadjuvant chemotherapy. The aim of the present study is to investigate the potential prognostic significance of the platelet-to-lymphocyte ratio in patients with gastric cancer receiving S-1 plus oxaliplatin or oxaliplatin and capecitabine regimen. Methods: Ninety-one patients with gastric cancer treated with neoadjuvant chemotherapy were enrolled in this study and then underwent operation. The optimal cutoff value was calculated using receiver-operating characteristic curve analyses. The optimal cutoff value of platelet-to-lymphocyte ratio was divided into low platelet-to-lymphocyte ratio Results: Kaplan-Meier analyses revealed that patients with low platelet-to-lymphocyte ratio correlated remarkably with better mean disease-free survival and mean overall survival than those with high platelet-to-lymphocyte ratio (mean disease-free survival 47.33 and 33.62 months, respectively; mean overall survival 51.21 and 36.80 months, respectively). The results demonstrated that platelet-to-lymphocyte ratio had prognostic significance using the cutoff value of 162 on disease-free survival and overall survival, and the mean disease-free survival and overall survival time for patients with low platelet-to-lymphocyte ratio were longer than those with high platelet-to-lymphocyte ratio. Meanwhile, patients with gastric cancer who had lower platelet-to-lymphocyte ratio had longer 1-, 3-, and 5-year rates of disease-free survival and overall survival. Moreover, patients with low platelet-to-lymphocyte ratio had longer mean disease-free survival and overall survival than those with high platelet-to-lymphocyte ratio in receiving S-1 plus oxaliplatin or oxaliplatin and capecitabine regimen. Conclusions: The preoperative platelet-to-lymphocyte ratio may be a promising and convenient prognostic biomarker for patients gastric cancer receiving S-1 plus oxaliplatin or oxaliplatin and capecitabine regimen neoadjuvant chemotherapy. It may be useful to help the doctors identify the high-risk patients for taking efficient treatment strategy decisions.

Background and Objectives Systemic failure remains a predominant issue in locally advanced rectal cancer (LARC). A new strategy using capecitabine and oxaliplatin (XELOX regimen) administered prior to and then concomitant to radiotherapy for high risk LARC is developed in our practice. The aim of the present study was to evaluate the short-term efficacy and toxicities of this strategy. Methods Patients were treated with one cycle XELOX regimen (oxaliplatin 130 mg/m2 on day 1 with capecitabine 1,000 mg/m2 twice daily for 14 days every 3 weeks), followed by chemoradiation (50 Gy over 5 weeks) with modified XELOX regimen (oxaliplatin dose reduction to 100 mg/m2), and total mesorectal excision. Tumor response, toxicities, and surgical complications were recorded. Results Forty-two patients treated with the strategy were identified. All patients completed planned dose of induction chemotherapy and concurrent chemoradiotherapy. Grade 3 toxicities were thrombocytopenia (4.8%), diarrhea (7.1%), proctitis (4.8%), and radiation dermatitis (7.1%). Five patients (12.5%) developed postoperative complications. Pathologic complete response (pCR) and nearly pCR were achieved in 7 (15.0%) and 13 patients (35.0%). Conclusions The preliminary results suggest that induction chemotherapy followed by chemoradiotherapy with capecitabine and oxaliplatin in LARC is well tolerated. The strategy achieves favorable short term outcome in terms of pCR and nearly pCR rate, which warrants further investigation. J. Surg. Oncol. 2014 109:478–482. © 2013 Wiley Periodicals, Inc.

Adenocarcinoma arising from the ampulla of Vater is a rare disease and has limited data regarding outcome of chemotherapy. The ampulla of Vater is a heterogeneous junctional structure located at the union of the common bile duct, the pancreatic duct, and the small intestine. Thus, ampullary adenocarcinoma is classified as either intestinal type or pancreatobiliary type. We investigated the efficacy of the XELOX (capecitabine plus oxaliplatin) chemotherapy in patients with recurrent or metastatic ampullary adenocarcinoma, and analyzed the histopathologic features and outcomes. From November 2009 to December 2011, 21 patients were treated with XELOX regimen. XELOX was administered in outpatient clinic every 3 weeks according to the following protocol: oral administration of capecitabine 750 mg/m² twice a day on days 1-14 and intravenous injection of oxaliplatin 130 mg/m² on day 1. With follow-up of median 16.6 months, median time to progression (TTP) was 7.6 months (95% confidence interval [CI], 6.7-8.5), and median overall survival was 19.7 months (95% CI, 14.8-23.6). Two patients (9%) achieved complete response and 6 patients (29%) showed partial response. In subgroup analysis with tissue specimens obtained from 17 patients, median TTP was longer among patients with the intestinal-type adenocarcinoma (n = 7), compared to those with the pancreatobiliary type (n = 10) (13.1 vs. 6.4 months, P = 0.038). The most common grade 3-4 adverse event was neutropenia (27%), and most events were mild. XELOX chemotherapy shows favorable efficacy with manageable toxicity for advanced intestinal-type ampullary adenocarcinoma.

The incidence of the para-aortic lymph node metastasis (PALM) in patients with advanced gastric cancer is 6 to 33 %. The prognosis is poor and the 5-year survival rate is only 12 to 23 % after gastrectomy with super-extended lymph node dissection. We applied an individualized comprehensive treatment for affected patients including neoadjuvant chemotherapy via intra-arterial and intravenous administration, surgery and radiotherapy, to investigate the safety and prognostic value. Between January 2005 and December 2010, 47 advanced gastric cancer patients with PALM received 5-Fu (370 mg/m2) and leucovorin (200 mg/m2) intravenously on days 1–5, and intra-arterial infusion of etoposide (80 mg/m2) and oxaliplatin (80 mg/m2) on days 6 and 20, repeated 2 cycles. Patients achieved PR or CR of the para-aortic lymph node (PAL) were performed D2 dissection, followed by 6 cycles chemotherapy with XELOX regimen, oxaliplatin (130 mg/m2) on day 1 and xeloda (1000 mg/m2) on days 1 to 14 of a 28-day cycle, and radiotherapy to the region of PALM. Forty-six patients completed 2 cycles of neoadjuvant chemotherapy. The overall response rate of the primary tumor was 80.4 % (37/46). The response rate of PAL was 76.1 % (35/46). Thirty-two patients underwent D2 dissection and six cases achieved pathological complete response (pCR). The toxicity profile was well tolerable and there was no treatment-related death. The median survival time for all patients was 23 months, and for nonsurgical and surgical patients were 12 and 29 months (p

Objective: This study aimed at assessing the efficacy and safety of oxaliplatin plus oral capecitabine (XELOX regimen) as first-line chemotherapy in elderly patients with advanced gastric cancer (AGC). Patients and Methods: Forty-six eligible patients aged ≧70 years with previously untreated AGC received oxaliplatin 130 mg/m2 intravenously over a 2-hour period on day 1 plus oral capecitabine 850 mg/m2 twice daily on days 1–14, every 3 weeks. Results: All patients were evaluable for toxicity and 45 patients for efficacy. A median of 6 cycles (range 1–8) was administered. The overall response rate was 48.9% (95% CI 34–64) with 1 complete response, 21 partial responses, 15 stable diseases and 8 progressions. Median time to progression was 6.0 months (95% CI 3.9–8.1), and the median overall survival was 10.0 months (95% CI 8.6–11.4). Toxicity was fairly mild. Grade 3 toxicities included neutropenia (6.5%), thrombocytopenia (2.2%), nausea (2.2%), vomiting (4.3%), diarrhea (4.3%) as well as peripheral neuropathy (2.2%); grade 4 toxicities occurred in none of the patients. Conclusion: The XELOX regimen with capecitabine at a lower dose of 850 mg/m2 is active, fairly tolerable and conveniently delivered as first-line chemotherapy for elderly AGC patients.

XELOX (oxaliplatin 130 mg/m(2) iv, capecitabine 1000 mg/m(2) bid oral d1-14, q3w) chemotherapy has never been used in children. In this report, we present a case of a 12-year-old girl with colon adenocarcinoma, treated with surgery and XELOX chemotherapy.On admission, the girl complained of abdominal pain and intestinal obstruction. Physical examination revealed a distended abdomen with tenderness on the left upper quadrant. Barium enema revealed a stenotic lesion at the distal end of the transverse colon, and abdominal computed tomography showed acute obstruction and a colonic mass. Laparotomy was performed after the failure of conservative treatment.The mass was originated from the transverse colon. Frozen sections of the specimens revealed an adenocarcinoma. Transverse colectomy was performed and regional lymph nodes were removed. Pathological examination confirmed that the mass was a poorly differentiated adenocarcinoma, and XELOX chemotherapy was used. No evidence of recurrent or metastatic tumor was found after 18 months.Although complete resection is the most effective treatment, XELOX chemotherapy is beneficial to the improvement of clinical outcome of patients with colon adenocarcinoma.

Either cetuximab or bevacizumab can improve the survival of patients with metastastic colorectal cancer (mCRC) if administered combided with cytotoxic agents. However, the effect of two or more target agents in combination is uncertain in these patients. Here, we reported a patient with mCRC successfully treated by a combination of target agents after the failure of chemotherapy. The patient received palliative resection of primary tumor followed by 9 cycles of postoperative XELOX regimen, cytokine-induced killer cell (CIK)-based biotherapy, traditional Chinese medicine, particle implantation in the lung metastatic lesions. The tumor progressed 20 months after the standard treatments. Then, the regimen cetuximab, bevacizumab and cefitinib was applied. During the treatment with targeted agents, grade IV acne-like rash and relatively severe parionychia of the toes occurred. Both of them recovered smoothly. The PET-CT reexamination at 40 days after the target treatment showed that the metabolism of mediastinal lymph nodes basically recovered to a normal level. The combination of multiple targeted agents obtained a progression-free survival(PFS) of 11 months and the patient with a good quality of life during this period.

Background There is no single standard chemotherapy regimen for elderly patients with advanced gastric cancer (AGC). A phase III trial has confirmed that both capecitabine monotherapy and capecitabine plus oxaliplatin are well tolerated for elderly patients with AGC, but their economic influence in China is unknown. Objective The purpose of this cost-effectiveness analysis was to estimate the effects of capecitabine monotherapy and capecitabine plus oxaliplatin in elderly patients with AGC on health and economic outcomes in China. Methods We created a Markov model based on data from a Korean clinical phase III trial to analyze the cost-effectiveness of the treatment of elderly patients in the capecitabine monotherapy (X) group and capecitabine plus oxaliplatin (XELOX) group. The costs were obtained from published reports and the local health system. The utilities were assumed on the basis of the published literature. Costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICER) were estimated. One-way and probabilistic sensitivity analyses (Monte Carlo simulations) were performed. Results In the cost-effectiveness analysis, X had a lower total cost ($45,731.68) and cost-effectiveness ratio ($65,918.93/QALY). The one-way sensitivity analysis suggested that the most influential parameter was the risk of requiring second-line chemotherapy in XELOX group. The probabilistic sensitivity analysis predicted that the X regimen was cost-effective 100% of the time, given a willingness-to-pay threshold of $26,598. Conclusions Our findings show that the XELOX regimen is less cost-effective compared to the X regimen for elderly patients with AGC in China from a Chinese healthcare perspective.