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A case-control study of a combination of single nucleotide polymorphisms and clinical parameters to predict clinically relevant toxicity associated with fluoropyrimidine and platinum-based chemotherapy in gastric cancer.
Cordova-Delgado, M, Bravo, ML, Cumsille, E, Hill, CN, Muñoz-Medel, M, Pinto, MP, Retamal, IN, Lavanderos, MA, Miquel, JF, Rodriguez-Fernandez, M, et al
BMC cancer. 2021;(1):1030
Abstract
BACKGROUND Fluoropyrimidine plus platinum chemotherapy remains the standard first line treatment for gastric cancer (GC). Guidelines exist for the clinical interpretation of four DPYD genotypes related to severe fluoropyrimidine toxicity within European populations. However, the frequency of these single nucleotide polymorphisms (SNPs) in the Latin American population is low (< 0.7%). No guidelines have been development for platinum. Herein, we present association between clinical factors and common SNPs in the development of grade 3-4 toxicity. METHODS Retrospectively, 224 clinical records of GC patient were screened, of which 93 patients were incorporated into the study. Eleven SNPs with minor allelic frequency above 5% in GSTP1, ERCC2, ERCC1, TP53, UMPS, SHMT1, MTHFR, ABCC2 and DPYD were assessed. Association between patient clinical characteristics and toxicity was estimated using logistic regression models and classification algorithms. RESULTS Reported grade ≤ 2 and 3-4 toxicities were 64.6% (61/93) and 34.4% (32/93) respectively. Selected DPYD SNPs were associated with higher toxicity (rs1801265; OR = 4.20; 95% CI = 1.70-10.95, p = 0.002), while others displayed a trend towards lower toxicity (rs1801159; OR = 0.45; 95% CI = 0.19-1.08; p = 0.071). Combination of paired SNPs demonstrated significant associations in DPYD (rs1801265), UMPS (rs1801019), ABCC2 (rs717620) and SHMT1 (rs1979277). Using multivariate logistic regression that combined age, sex, peri-operative chemotherapy, 5-FU regimen, the binary combination of the SNPs DPYD (rs1801265) + ABCC2 (rs717620), and DPYD (rs1801159) displayed the best predictive performance. A nomogram was constructed to assess the risk of developing overall toxicity. CONCLUSION Pending further validation, this model could predict chemotherapy associated toxicity and improve GC patient quality of life.
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Efficacy of Chinese herbal injections combined with fluoropyrimidine and oxaliplatin-based chemotherapy for advanced colorectal cancer: A protocol for systematic review and meta-analysis of randomized controlled trials.
Wang, S, Wang, X, Zhang, Y, Zhou, T, Hu, S, Tian, P, Li, Z, Li, Y, Gui, Y, Dong, J, et al
Medicine. 2020;(52):e23550
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Abstract
BACKGROUND Fluoropyrimidine combined with oxaliplatin-based chemotherapy have become the first-line treatment for advanced colorectal cancer (CRC). Chinese herbal injections (CHIs), as an important part of TCM, have been widely applied as adjunctive treatments to chemotherapy in patients with advanced CRC. However, the efficacy of this combination therapy has not been evaluated comprehensively. METHODS We will conduct this systematic review and meta-analysis in accordance with the Preferred Reported Items for Systematic Review and Meta-analysis (PRISMA) guidelines. 7 databases will be searched for related randomized controlled trials (RCTs) from their inception to August 31, 2020: PubMed, Cochrane Library, EMBASE, China National Knowledge Infrastructure (CNKI), VIP Database for Chinese Technical Periodicals (VIP), SinoMED and Wanfang Database. Two researchers will perform study selection, data extraction, and assessment of risk of bias independently. The primary outcomes are the disease control rate (DCR) and the objective response rate (ORR), the secondary outcomes are progression-free survival (PFS), survival rate, quality of life (QoL) and adverse effects. Cochrane Review Manager (RevMan 5.3) software will be used to analyze the outcomes. RESULTS AND CONCLUSION This systematic review will evaluate the efficacy of CHIs and fluoropyrimidine and oxaliplatin-based chemotherapy for advanced CRC so as to provide valuable evidence to the application of CHIs in advanced CRC. SYSTEMATIC REVIEW REGISTRATION INPLASY registration number: INPLASY2020100050.
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The clinical value and usage of inflammatory and nutritional markers in survival prediction for gastric cancer patients with neoadjuvant chemotherapy and D2 lymphadenectomy.
Li, Z, Li, S, Ying, X, Zhang, L, Shan, F, Jia, Y, Ji, J
Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association. 2020;(3):540-549
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BACKGROUND The clinical values of inflammatory and nutritional markers remained unclear for gastric cancer with neoadjuvant chemotherapy (NACT). METHODS The inflammatory, nutritional markers and their changes were analyzed for locally advanced gastric cancer with NACT. The predictive value was evaluated by the Cox proportional hazards regressions under three hypothesized scenarios. The nomograms including independent prognostic factors were plotted for survival prediction. RESULTS A total of 225 patients were included in the study. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index, and hemoglobin (Hgb) were significantly reduced, and the body mass index was significantly increased after NACT (all P < 0.05). The pre-NACT NLR [hazard ratio (HR) = 1.176, P = 0.059] showed a trend to correlate with the overall survival (OS) when only pre-NACT markers available; The post-NACT Hgb (HR = 0.982, P = 0.015) was the independent prognostic factor when only post-NACT markers available; The post-NACT Hgb (HR = 0.984, P = 0.025) and the change value of LMR (HR = 1.183, P = 0.036) were the independent prognostic factors when both pre- and post-NACT markers available. The nomogram had a similar Harrell's C-statistic compared to ypTNM stage (0.719 vs. 0.706). CONCLUSION For locally advanced gastric cancer, the NACT could significantly decrease some inflammatory markers. The pre-NACT NLR, the post-NACT Hgb and the change value of LMR had some values in survival prediction combined with age, sex, tumor location and the clinical stages under different clinical scenarios. The elevated initial NLR, the preoperative anemia and the greater change value of LMR implied a poor prognosis.
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Transcriptome Alterations in Liver Metastases of Colorectal Cancer After Acquired Resistance to Cetuximab.
Li, Z, Chen, Y, Ren, WU, Hu, S, Tan, Z, Wang, Y, Chen, Y, Zhang, J, Wu, J, Li, T, et al
Cancer genomics & proteomics. 2019;(3):207-219
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BACKGROUND/AIM: Cetuximab in combination with chemotherapy is recommended as first-line therapy for metastatic colorectal cancer (mCRC) with wild-type RAS. However, drug resistance to cetuximab exists widely in mCRC and reduces the prognosis of patients. Although some genomic alterations have been demonstrated to drive acquired resistance to cetuximab, the overall compendium of inherent molecular mechanisms is still incomplete. MATERIALS AND METHODS Four liver metastasis biopsies were collected from two mCRC patients who were treated with cetuximab in combination with 5-fluororacil plus leucovorin and oxaliplatin (FOLFOX) regimen. RESULTS Transcriptomic analysis revealed global gene expression alterations between paired samples prior to treatment and after acquired resistance. Further bioinformatics analysis discovered differentially expressed protein-coding genes/lncRNAs/miRNAs, potential miRNA-mRNA regulatory networks and lncRNA-mRNA competing endogenous RNA network, which may be potential biomarkers or play roles during the process of acquired resistance to cetuximab. CONCLUSION Our study contributes to deciphering the molecular mechanisms of acquired resistance to cetuximab.
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Effects of sequential chemotherapy of FOLFIRI/FOLFOX on the endocrine axes of ACTH-cortisol and renin-angiotensin-aldosterone.
Huang, C, Jiang, Y, Duan, G, Li, Z, Chen, L, Wang, X
Journal of neuro-oncology. 2012;(3):485-90
Abstract
The chemotherapies of FOLFOX (leucovorin + 5-fluorouracil + oxaliplatin) and FOLFIRI (folinic acid + 5-fluorouracil + irinotecan) are effective for a variety of malignant tumors. In particular, the sequential chemotherapy of FOLFOX/FOLFIRI has become the preferred post-operational treatment approach for gastrointestinal cancer and an important palliative care program for advanced cancer. However, the sequential chemotherapy of FOLFOX/FOLFIRI showed severe side effects due to the fact that the toxicity of the drugs can be enhanced by each other. Here, we report the dynamic changes in the activities of serum ACTH, cortisol, renin, angiotensin, and aldosterone in patients following multiple cycles of FOLFOX/FOLFIRI sequential chemotherapy. We found that the sequential chemotherapy might cause damage to the activities of the endocrine cells and/or the sympathetic nerve, and alter endocrine function, specifically the ACTH-cortisol and renin-angiotensin-aldosterone axes.
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Thalidomide improves prevention of chemotherapy-induced gastrointestinal side effects following a modified FOLFOX7 regimen: results of a prospective randomized crossover study.
Liu, Y, Zhang, J, Teng, Y, Zhang, L, Yu, P, Jin, B, Zhao, M, Shi, J, Liu, S, Song, N, et al
Tumori. 2009;(6):691-6
Abstract
AIMS AND BACKGROUND Thalidomide was firstly evaluated for the control of chemotherapy-induced gastrointestinal side effects following a modified FOLFOX7 (mFOLFOX7) regimen. METHODS AND STUDY DESIGN Chemotherapy-naive patients with malignant tumors were randomized into two groups: A-B group (A, 0.3 mg of ramosetron plus 10 mg of dexamethasone on day 1, was given intravenously in the first cycle, and B, 0.3 mg of ramosetron plus 10 mg of dexamethasone on day 1 intravenously plus 150 mg orally twice daily of thalidomide on days 2 through 5, in the second cycle) and B-A group (those drugs were given in the reverse sequence). The primary end point was the efficacy of thalidomide in controlling delayed (days 2 through 5) chemotherapy-induced nausea and vomiting (CINV). The secondary end point was the safety of thalidomide. RESULTS Of 52 patients enrolled, 50 patients (96%) were assessable. Complete response rates of delayed nausea (no nausea) were higher with group B than group A (52% vs 24%, P = 0.004 on day 2; 58% vs 24%, P = 0.001 on day 3; and 60% vs 36%, P = 0.016 on day 4). Complete response rates of delayed emesis (no emetic episodes, no rescue therapy) for group B and A also showed significance (86% vs 66%, P = 0.019 on day 2 and 76% vs 56%, P = 0.035 on day 3). Complete response rates on anorexia for group B were higher than those for group A on days 2 through 5. More patients in group B reported sedation or dizziness than in group A (42% vs 9.6%; P = 0.000). CONCLUSIONS Thalidomide improves prevention of chemotherapy-induced gastrointestinal side effects following the mFOLFOX7 regimen. It is a safe, effective antiemetic.