Chemotherapy Regimen For Gastric Cancer Research Articles

Impact of Laparoscopic Gastrectomy on the Completion Rate of the Perioperative Chemotherapy Regimen in Gastric Cancer: A Swedish Nationwide Study

BackgroundOmission of prescheduled chemotherapy following surgery for gastric cancer is a frequent clinical problem. This study examined whether laparoscopic gastrectomy (LG) had a positive impact on compliance with adjuvant chemotherapy compared with open (OG).MethodsPatients with cT2-4aN0-3M0 adenocarcinoma treated with gastrectomy and perioperative chemotherapy between 2015 and 2020 were identified in the Swedish national register. Additional information regarding chemotherapy was retrieved from medical records. Regression models were used to investigate the association between surgical approach and the following outcomes: initiation of adjuvant chemotherapy, modification, and time interval from surgery to start of treatment.ResultsA total of 247 patients were included (121 OG and 126 LG, conversion rate 11%), of which 71.3% had performance status ECOG 0 and 77.7% clinical stage II/III. In total, 86.2% of patients started adjuvant chemotherapy, with no significant difference between the groups (LG 88.1% vs OG 84.3%, p = 0.5). Reduction of chemotherapy occurred in 37.4% of patients and was similar between groups (LG 39.4% vs OG 35.1%, p = 0.6), as was the time interval from surgery. In multivariable analysis, LG was not associated with the probability of starting adjuvant chemotherapy (OR 1.36, p = 0.4) or the need for reduction (OR 1.29, p = 0.4). Conversely, major complications had a significant, negative impact on both outcomes.ConclusionsThis nationwide study demonstrated a high rate of adjuvant chemotherapy initiation after curative intended surgery for gastric cancer. A beneficial effect of LG compared with OG on the completion rate was not evident.

Analysis of the efficacy and influencing factors of preoperative P-SOX neoadjuvant chemotherapy regimen for progressive gastric cancer-construction of a clinical prediction model.

Preoperative neoadjuvant chemotherapy is one of the most common treatments for patients with advanced gastric cancer that cannot be completely removed by surgery. Nab-paclitaxel is a nano-formulation of paclitaxel that has been shown to be effective in treating stomach cancer. In addition, oxaliplatin + S-1 (SOX) has been a first-line chemotherapy regimen for gastric cancer, and it has the effect of tumor downstaging, improving the R0 resection rate, and reducing the postoperative recurrence rate, but the side effects are significant. During the application of oxaliplatin, obvious gastrointestinal reactions such as nausea and vomiting can be observed. There may also be blood system side effects such as leukopenia and thrombocytopenia, as well as serious adverse reactions such as peripheral neuropathy. Therefore, we reduced the amount of oxaliplatin in SOX and added nab-paclitaxel on the basis of this, in order to increase the efficacy while reducing the side effects of SOX regimen. We selected 192 patients with advanced gastric cancer admitted to the Department of Gastrointestinal Oncology of Qinghai University Hospital from July 2019 to February 2022, and all were treated with nab-paclitaxel plus oxaliplatin + S-1 neoadjuvant chemotherapy regimen, and underwent further surgery after chemotherapy. The tumor regression grade (TRG grade) and response evaluation criteria of solid tumor 1.1 (RECIST1.1) were taken as the dependent variables. According to TRG classification, 120 patients were effective (grade 0, 1, 2 = 62.50%, age: 55.63 ± 9.02 years), 72 patients were ineffective (grade 3 = 37.50%, 55.82 ± 9.21 years), and the effective rate of chemotherapy was 62.50%. According to RECIST1.1, 116 patients were effective (CR + PR = 60.42%, mean age 55.84 ± 9.02 years), 76 patients were ineffective (SD + PD = 39.58%, 55.47 ± 9.19 years), and the effective rate was 60.42%. The factors p < 0.2 in univariate logistic regression analysis were included in multivariate logistic regression analysis, and p < 0.05 was the statistical difference, and statistically significant factors were screened out for modeling and plotted the nomogram. Among them, in the tumor regression grade, the final factors related to effective chemotherapy are the degree of differentiation, cT. stage, tumor diameter, chemotherapy cycle, and the final factors related to effective chemotherapy in the solid tumor response evaluation criteria are the degree of differentiation, cT. stage, tumor diameter. Therefore, we conclude that the regimen of nab-paclitaxel combined with oxaliplatin and S-1 has certain positive significance in the treatment of advanced gastric cancer.

Correlation between mismatch repair and survival of patients with gastric cancer after 5-FU-based adjuvant chemotherapy.

Almost all adjuvant chemotherapy regimens for gastric cancer recommended by guidelines are fluorouracil (5-FU) based, and 5-FU-based adjuvant chemotherapy plays an important role in reducing the recurrence of gastric cancer after surgery. However, the effect of mismatch repair (MMR) status on survival after 5-FU-based adjuvant chemotherapy in patients with gastric cancer remains controversial. We prospectively included patients with gastric cancer who underwent radical gastrectomy between March 14, 2017 and September 30, 2021. The included patients received 5-FU-based adjuvant chemotherapy or surgery alone. The MMR status of patients was divided into MMR proficient (pMMR) and MMR defective (dMMR) according to four MMR proteins. Peripheral blood was collected for systemic inflammation analysis. The main purpose of this study was to analyze the effect of MMR status on survival after 5-FU-based adjuvant chemotherapy in patients with gastric cancer. We also analyzed the differences in systemic inflammation levels in different MMR status and their impact on survival. A total of 479 patients were enrolled, with a median follow-up period of time was 36months. In the surgery alone group, dMMR gastric cancer had better disease-free survival (DFS) (hazard ratio [HR] = 4.33, 95% confidence interval [CI] 1.25-15.02, p = 0.02) than pMMR, and in the adjuvant chemotherapy group, there was no significant difference in DFS (HR = 1.16, 95% CI 0.65-2.07, p = 0.61) between dMMR and pMMR gastric cancer. The same results were seen for overall survival (OS). In addition, the result show that in the dMMR group, there was no difference in DFS (HR = 1.62, 95% CI 0.46-5.77, p = 0.45) between patients receiving adjuvant chemotherapy and those receiving surgery alone. In the pMMR group, the DFS values (HR = 0.59, 95%CI 0.35-0.99, p = 0.04) of patients receiving adjuvant chemotherapy were better than those of patients receiving surgery alone, and the same results were observed for OS. In addition, among pMMR patients, patients with a low platelet lymphocyte ratio (PLR) who received 5-FU adjuvant chemotherapy and those with a low neutrophil lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) who received surgery alone had better DFS and OS. To our knowledge, this is the first prospective study to specifically explore the correlation between MMR and survival of patients with gastric cancer after 5-FU-based adjuvant chemotherapy. The results showed that gastric cancer patients with pMMR can benefit from 5-FU-based adjuvant chemotherapy, but those with dMMR cannot. Among pMMR patients, lower PLR and SII values with surgery alone and lower NLRs in those receiving 5-FU-based adjuvant chemotherapy were associated with higher DFS and OS.

Decitabine and Cisplatin are Synergistic to Exert Anti-Tumor Effect on Gastric Cancer via Inducing Sox2 DNA Demethylation.

BackgroundCisplatin is a vital chemotherapy regimen for gastric cancer (GC), while partial response is observed (approximately 40%) because of drug resistance. Thus, it is urgent to improve drug sensitivity to improve the therapeutic effect of cisplatin on GC.PurposeThe study was performed to explore the synergistic effect of decitabine and cisplatin in GC.Materials and MethodsCancer and matched adjacent tissues from patients with GC were obtained and quantitative real-time PCR (qRT-PCR), Western blot and immunohistochemistry were performed to evaluate Sox2 expression level. Methylation-specific PCR (MSP) was performed to assess the effect of 5-aza-2ʹ-deoxycytidine (5-Aza-CdR) on Sox2 promoter. Cell proliferation assay, scratch-wound migration assay and Transwell invasion ability were performed to assess the effect of 5-Aza-CdR on proliferation, migration and invasion ability. Meantime, the effect of 5-Aza-CdR was also investigated in gastric cell lines BGC-823 and nude mouse xenograft tumor model. Finally, the anti-cancer effect of decitabine, cisplatin and their combination treatment were investigated in a BGC-823 and nude mouse xenograft tumor model, Sox2 methylation level, Sox2 expression of BGC-823 and xenograft tumors were analyzed by MSP, qRT-PCR and Western blot.ResultsSox2 expression was significantly associated with different differentiated degrees, depth of invasion (0.0011), lymph node metastasis (0.0013), and TNM stage (0.0002). Next, methylation inhibitor 5-Aza-CdR restored Sox2 expression to promote proliferation, migration and invasion in vitro and in vivo. Finally, cisplatin and decitabine was found to be synergistic to inhibit proliferation of xenograft tumors. Likewise, cisplatin and decitabine were also synergistic to induce Sox2 DNA demethylation to promote Sox2 mRNA and protein expression in BGC-823 and xenograft tumors.ConclusionCisplatin and decitabine could be synergistic to induce Sox2 DNA demethylation to promote expression of the Sox2 gene, which exerted an anti-tumor effect on GC. It may suggest an insight for innovative therapeutics of GC.

BRD9 controls the oxytocin signaling pathway in gastric cancer via CANA2D4, CALML6, GNAO1, and KCNJ5.

BackgroundFirst-line chemotherapeutic agents lead to remarkable activation treatment in cancers, but the side effects of these drugs also damage healthy cells. In some cases, drug resistance to chemotherapeutic agents is induced in cancer cells. The molecular mechanisms underlying such a side effect have been studied in a range of cancer types, yet little is known about how the adverse effects of chemotherapeutic drugs can be diminished by targeting bromodomain-containing protein 9 (BRD9) in gastric cancers.MethodsWe used two gastric cancer cell lines (MGC-803 and AGS) for comparison. We applied molecular and cellular techniques to measure cell survival and mRNA expression, investigated clinical data in the consensus of The Cancer Genome Atlas, and utilized high-throughput sequencing in MGC-803 cells and AGS cells for global gene expression analysis in inhibiting BRD9 conditions.ResultsOur studies showed that cancer cells with BRD9 overexpression, MGC-803 cells, were more sensitive to BRD9 inhibitors (i.e., BI9564 or BI7273) than AGS cells. The mechanism of BRD9 was related to the regulation of calcium voltage-gated channel auxiliary subunit alpha2 delta 4 (CANA2D4), calmodulin-like 6 (CALML6), guanine nucleotide binding protein (G protein), alpha activating activity polypeptide O (GNAO1) and Potassium Inwardly Rectifying Channel Subfamily J, Member 5 (KCNJ5) oncogenes in the oxytocin signaling pathway. BRD9 inhibitors could enhance the sensitivity of gastric cancer MGC-803 cells to adriamycin and cisplatin, so we may reduce the dosage of chemotherapeutic agents in curing gastric cancers with BRD9 over expression by combining BI9564 or BI7273 with adriamycin or cisplatin.ConclusionsOur study elucidated the feasibility and effectiveness of inhibiting BRD9 to reduce the adverse effects of first-line chemotherapeutic agents in treating gastric cancer with BRD9 overexpression. This study provides a scientific theoretical basis for a chemotherapy regimen in gastric cancer with BRD9 overexpression.

Tumor Treating Fields (150 kHz) combined with FOLFOX inhibits gastric cancer in vitro

Introduction: Gastric cancer is the fourth most common cancer and the second most common cause of cancer death worldwide. Despite recent improvements in systemic therapies, long‐term survival rates for patients with advanced gastric cancer remains poor. Tumor Treating Fields (TTFields) therapy is an approved anti-neoplastic treatment modality delivered via noninvasive application of low intensity, intermediate frequency, alternating electric fields. TTFields is a loco-regional treatment that targets rapidly dividing cells by disrupting microtubules leading to mitotic catastrophe, abnormal chromosome segregation and the induction of various forms of cancer cell death. FOLFOX (Oxaliplatin, 5-FU and Leucovorin) is an approved chemotherapy regimen for gastric cancer. We investigated the potential use of TTFields alone and in combination with FOLFOX for gastric carcinomas. Methods: AGS and KATO III gastric cells were treated for 72 hours with TTFields (1.1 and 1.7 V/cm, respectively) at various frequencies using the in-vitro system. Efficacy of the combined treatment of TTFields and FOLFOX and its individual components was tested by applying TTFields at the optimal frequency in combination with various drug concentrations. Cell counts, induction of apoptosis, clonogenic potential and overall effect were determined at the end of treatment. Results: The optimal TTFields frequency leading to the highest reduction in cell counts was 150 kHz for both cell lines: 55% and 52% reduction in cell counts for AGS and KATO III, respectively. The clonogenic potential of both cell lines was reduced by more than 70%. The combined treatment of TTFields with each FOLFOX component (Oxaliplatin, 5-FU or Leucovorin) led to a significant reduction in the survival of AGS and KATO III cells (2-way ANOVA, p < 0.001 for both cell lines) as compared to each treatment alone. The combined treatment of TTFields with FOLFOX led to further reduction in the overall effect (cytotoxic and clonogenic) of AGS (79%) compared to TTFields alone (65%) and FOLFOX alone (34%). Similar results were observed for the combined treatment of TTFields and FOLFOX in KATO III cells. Conclusion: These results presented demonstrate that TTFields can be an effective treatment against gastric cancer. The combination of TTFields with FOLFOX may further enhance treatment efficacy. There is a strong rationale to continue exploring the potential use of TTFields in combination with standard of care for the treatment of gastric cancer in the clinical settings.

Adjuvant chemotherapy with S-1 plus oxaliplatin improves survival of patients with gastric cancer after D2 gastrectomy: A multicenter propensity score-matched study.

AIMTo investigate the safety and efficacy of S-1 plus oxaliplatin (SOX) as an adjuvant chemotherapy regimen in gastric cancer (GC) after D2 dissection.METHODSGC Patients who underwent D2 gastrectomy from September 2009 to December 2011 in four Chinese institutions were enrolled. Patients with stage IB-IIIC GC, who received adjuvant SOX treatment were matched by propensity scores with those who underwent surgery alone and those who conducted capecitabine plus oxaliplatin (XELOX) regimen. Disease-free survival (DFS) and overall survival (OS) were compared among the groups. In addition, adverse events in SOX patients were analyzed.RESULTSOf 1944 GC patients who underwent D2 dissection, 867 were included for analysis. One hundred and seventeen patients treated with SOX were matched to 234 patients who conducted surgery alone. Fifty-seven patients treated with SOX were matched to 57 patients who received XELOX. The estimated five-year DFS was 57.5% in the adjuvant SOX group which was higher than that (44.6%) in the surgery alone group (P = 0.001); and the estimated five-year OS was 68.3% which was higher than that (45.8%) of surgery alone group (P < 0.001). Survival benefit was also revealed in stage III and > 60 years old subgroups (P < 0.001 and P = 0.015, respectively). Compared with XELOX regimen, SOX showed no significant difference in DFS (P = 0.340) and OS (P = 0.361). The most common ≥ 3 grade adverse events of SOX regimen were neutropenia (22.6%), leukopenia (8.9%) and thrombocytopenia (5.6%).CONCLUSIONCompared with surgery alone, SOX regimen significantly improves the long-term survival and has acceptable toxicity in patients with stage IB-IIIC GC after D2 dissection. It may be a novel adjuvant chemotherapy regimen in GC patients.

Original article: role of adjuvant chemotherapy in a perioperative chemotherapy regimen for gastric cancer.

BackgroundMultimodal treatment strategies – perioperative chemotherapy (CTx) and radical surgery – are currently accepted as treatment standard for locally advanced gastric cancer. However, the role of adjuvant postoperative CTx (postCTx) in addition to neoadjuvant preoperative CTx (preCTx) in this setting remains controversial.MethodsBetween 4/2006 and 12/2013, 116 patients with locally advanced gastric cancer were treated with preCTx. 72 patients (62 %), in whom complete tumor resection (R0, subtotal/total gastrectomy with D2-lymphadenectomy) was achieved, were divided into two groups, one of which receiving adjuvant therapy (n = 52) and one without (n = 20). These groups were analyzed with regard to survival and exclusion criteria for adjuvant therapy.ResultsPostoperative complications, as well as their severity grade, did not correlate with fewer postCTx cycles administered (p = n.s.). Long-term survival was shorter in patients receiving postCTx in comparison to patients without postCTx, but did not show statistical significance. In per protocol analysis by excluding two patients with perioperative death, a shorter 3-year survival rate was observed in patients receiving postCTx compared to patients without postCTx (3-year survival: 71.2 % postCTx group vs. 90.0 % non-postCTx group; p = 0.038).ConclusionThese results appear contradicting to the anticipated outcome. While speculative, they question the value of post-CTx. Prospectively randomized studies are needed to elucidate the role of postCTx.

Inter-institutional heterogeneity in outcomes of chemotherapy for metastatic gastric cancer: correlative study in the JCOG9912 phase III trial

BackgroundThe standard chemotherapy regimen for gastric cancer has been established by several phase III trials. However, few studies have evaluated inter-institutional heterogeneity in randomised trials; such research may assure the generalisability of the results and also the reliability of the study group itself.Patients and methodsThe Japan Clinical Oncology Group (JCOG)9912 phase III trial compared irinotecan plus cisplatin and S-1 alone with fluorouracil alone for metastatic gastric cancer, and finally demonstrated the non-inferiority of S-1 alone with respect to overall survival (OS). Mixed effects models were used to evaluate outcomes of 658 patients from 22 hospitals. After adjustment for nine background factors, the heterogeneity in OS, progression-free survival (PFS), and incidences of grade 3–4 adverse events among hospitals was estimated. We also estimated the correlation between outcomes and either hospital volume or medical oncology clinical experience.ResultsA large degree of heterogeneity in median OS was observed for fluorouracil alone (range, 8.3–13.3 months), while the difference in median PFS between hospitals was small (range, 2.4–3.4 months). Although some heterogeneity in the treatment effect of irinotecan plus cisplatin or S-1 alone was observed in OS and PFS, the HRs did not exceed 1.00 in any hospital for either regimen. There was minimal heterogeneity in the incidences of grade 3–4 adverse events. There was a trend towards correlation between greater medical oncology clinical experience and both better OS after fluorouracil alone and a lower HR for OS after irinotecan plus cisplatin, but it was not statistically significant.ConclusionsLarge inter-institutional heterogeneity was observed in OS, but not in PFS, after the standard regimen, but there was little heterogeneity in the treatment effects of irinotecan plus cisplatin or S-1 alone, indicating that the final results of the JCOG9912 trial can be generalised to the target population.Trial registration numberNCT00142350.

A phase I/II study of S-1 plus cisplatin in patients with advanced gastric cancer: 2-week S-1 administration regimen

The combination of a new oral dihydropyrimidine dehydrogenase-inhibitory fluoropyrimidine (S-1) and cisplatin (CDDP) is one of the most active chemotherapy regimens for gastric cancer. However, the optimum schedule for this combination has not yet been determined. This study was conducted to establish the maximum tolerated dose (MTD) and the recommended dose of CDDP when combined with 2-week S-1 administration, and to observe the safety and efficacy of the regimen as treatment for patients with advanced gastric cancer. S-1 was administered orally at a dose of 80 mg/m2 per day for 2 weeks, followed by a 2-week rest. CDDP was administered intravenously on day 8 of each course; the initial dose of CDDP was 60 mg/m2 and it was increased in 10-mg/m2 increments. Treatment was repeated every 4 weeks unless disease progression was observed. Eleven patients were enrolled. The main toxicities were leucopenia, neutropenia, nausea, and anorexia. These toxicities were not severe, and were reversible and manageable. The MTD for CDDP was established as 80 mg/m2, as 2 of 5 (40%) patients developed dose-limiting toxicity (DLT) at this level. Therefore, the recommended dose of CDDP was determined to be 70 mg/m2. All 11 patients were evaluable for a response: 8 achieved a partial response and 1 had stable disease. The overall response rate was 73%. This regimen is considered to be generally well-tolerated and has substantial antitumor activity.

Which chemotherapy regimen for gastric cancer?

Which chemotherapy regimen for gastric cancer?