A phase II study of a modified FOLFOX6 regimen as neoadjuvant chemotherapy for locally advanced gastric cancer

Wang, Xiang; Zhao, Lin; Liu, Hongfeng; Zhong, Dingrong; Liu, Wei; Shan, Guangliang; Dong, Fen; Gao, Wenjing; Bai, Chunmei; Li, Xiaohua

doi:10.1038/bjc.2016.126

Cited by 34 publications

(46 citation statements)

References 42 publications

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“…GC is the most common malignancy of the digestive system with high incidence and high mortality. [ 19 ] Although a combination of neoadjuvant chemoradiotherapy, [ 20,21 ] molecular‐targeted therapy, [ 22 ] and immunotherapy [ 23 ] has been developed for the diagnosis of advanced‐stage disease, there is still no effective approach to monitor and treat GC fundamentally. CircHIAT1 is an important circRNA with potential antitumor function, which has been proved to work as a tumor suppressor in renal cell carcinoma.…”

Section: Discussionmentioning

confidence: 99%

Circular RNA circHIAT1 inhibits proliferation and epithelial‐mesenchymal transition of gastric cancer cell lines through downregulation of miR‐21

Quan

Dong

Lun

et al. 2020

J Biochem & Molecular Tox

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Gastric cancer (GC) is the third leading cause of cancer‐related death worldwide. Circular RNA circHIAT1 has been proved to play an antitumor role. We aimed to explore the function and mechanism of circHIAT1 in GC. MKN28 and MKN45 cells were transfected with PLCDH‐circHIAT1, miR‐21 mimic, and relative control. Cell viability and apoptosis were examined through Cell Counting Kit‐8 and flow cytometry, respectively. CircHIAT1 expression and other relative factors were tested through quantitative reverse transcription‐polymerase chain reaction and Western blot analysis, respectively. Our findings demonstrated that circHIAT1 was lowly expressed in GC tissues. After transfection with PLCDH‐circHIAT1 in MKN28 and MKN45 cells, cell viability was decreased, while the expression levels of p53 and p21 were raised, as well as apoptosis. Besides this, the epithelial‐mesenchymal transition process was inhibited by PLCDH‐circHIAT1 transfection. Mechanistically, miR‐21 expression was upregulated in GC tissues and could be negatively regulated by circHIAT1. Further experiments showed that the addition of miR‐21 mimic reversed the growth inhibition effects of circHIAT1 overexpression. Moreover, circHIAT1 inhibited the activation of phosphatase and tensin homolog/phosphatidylinositol 3 kinase/protein kinase B and extracellular signal‐regulated kinase signal pathways via downregulating miR‐21. CircHIAT1 functioned as a tumor inhibitor in GC cells through downregulating miR‐21, and could be a novel target for GC treatment.

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Section: Discussionmentioning

confidence: 99%

Circular RNA circHIAT1 inhibits proliferation and epithelial‐mesenchymal transition of gastric cancer cell lines through downregulation of miR‐21

Quan

Dong

Lun

et al. 2020

J Biochem & Molecular Tox

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“…Neoadjuvant treatment has been effective in the treatment of several malignant tumors and is part of the standard treatment for breast, esophageal, and gastric cancers (11-14,21). In locally advanced disease, preoperative chemotherapy might reduce tumor size, eradicate micrometastases, and improve operability and surgical downstaging (14-17).…”

Section: Discussionmentioning

confidence: 99%

“…In locally advanced disease, preoperative chemotherapy might reduce tumor size, eradicate micrometastases, and improve operability and surgical downstaging (14-17). …”

Section: Discussionmentioning

confidence: 99%

“…Recently several studies showed that neoadjuvant chemotherapy (NAC) is an effective treatment option for aggressive solid tumors including resectable and unre-sectable tumors, such as gastroesophageal cancer, gastric cancer and breast cancer (11-14). It is thought to confer an advantage over other treatment regiments through the eradication of potential micrometastases or circulating tumor cells; reduction of surgical tumor cell shedding; improvement of complete resection rate owing to primary tumor regression; maintenance of chemotherapy intensity; evaluation of chemotherapy safety and chemosensitivity, thereby contributing to the assessment of the need for postoperative chemotherapy or selection of the appropriate chemotherapy regimen; and the circumvention of delayed postoperative chemotherapy owing to surgical compli-cations (14-17).…”

Section: Introductionmentioning

confidence: 99%

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CapOX as neoadjuvant chemotherapy for locally advanced operable colon cancer patients: a prospective single-arm phase II trial

Liu

et al. 2016

Chinese Journal of Cancer Research

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ObjectiveThe aim of this prospective, single-arm phase II trial was to confirm the safety and efficacy of neoadjuvant chemotherapy (NAC) using oxaliplatin plus capecitabine (CapOX) for patients with operable locally advanced colon cancer (CC).MethodsPatients with computed tomography-defined T4 or lymph node-positive CCs were enrolled. After radiological staging, patients were treated with at least 2 cycles of NAC consisting of 130 mg/m2 oxaliplatin on d 1, plus 1,000 mg/m2 capecitabine twice daily for 14 d every 3 weeks, followed by surgery, and then with the rest cycles of adjuvant chemotherapy. Radiological response was evaluated after 2 cycles of NAC. Tumor response, treatment toxicity, and surgical complications were recorded. The pathological response to therapy was evaluated according to the tumor regression grade (TRG) score. The primary endpoint was pathologic tumor response. This trial is registered in ClinicalTrials.gov (No: NCT02415829).ResultsForty-seven patients were enrolled in the study. Forty-two patients completed the planned treatments. The total radiological response rate was 68% (32/47), including complete and partial response rates of 2% (1/47) and 66% (31/47), respectively. Stable disease was observed in 32% (15/47) and progressive disease was observed in none. Complete pathologic response, major regression, and at least moderate regression were achieved in 1 (2%), 2 (4%), and 29 (62%) patients, respectively. Four patients developed grade 3 treatment toxicities. One patient with wound infection occurred after operation (1/47, 2%). There was no treatment-related death.ConclusionsOur results suggest that NAC with CapOX is an effective and safe treatment option for patients with locally advanced CCs.

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“…The clinicopathological factors that predict prognosis have been discussed in several studies, and histological response and ypTNM stage after neoadjuvant therapy are generally considered effective predictors (15)(16)(17)(18)(19)(20)(21)(22)(23)..Yukinori compared the prognostic value of evaluation criteria, the Response Evaluation Criteria in Solid Tumors (RECIST) standard, the Japanese Classification of Gastric Cancer (JCGC) standard and the histological response. A total of 100 patients were included in the JCOG0210 and JCOG0405 studies.…”

Section: Discussionmentioning

confidence: 99%

Downstaging depth score as a better surrogate endpoint than pCR, histological response and ypN0 for long-term outcomes in locally advanced gastric cancer patients after preoperative chemo-radiotherapy

Li¹,

Wang²,

Tang³

et al. 2020

Preprint

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Background: The prediction effect of preoperative chemo-radiotherapy(CRT) is not high and difficult to guide individualized treatment. We explored a surrogate endpoint for long-term outcomes in locally advanced gastric cancer patients after preoperative CRT. Methods: From April 2012 to April 2019, 95 patients enrolled in 4 prospective studies with locally advanced gastric cancer who received preoperative concurrent radio-chemotherapy were included. All patients were stage T3/4, N+. Local control (LC), distant metastasis-free survival (DMFS), disease-free survival (DFS) and overall survival (OS) were evaluated. The clinicopathological factors related to the long-term prognosis were analysed by uni- and multivariant analyses. The downstaging depth score (DDS), a novel method of evaluating the CRT response, was used to predict long-term outcomes. Results: The median follow-up period for survivors was 30 months. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve predicted by the DDS was 0.728, which was better than that of pathological complete response (pCR), histological response and ypN0 (AUC= 0.634, 0.640 and 0.643, respectively). The DDS cut-off value was 4. pCR and ypN0 were associated with OS (p = 0.026, 0.049). Surgery and the DDS were correlated with DMFS, DFS and OS (p = 0.001, 0.000, and 0.000 and 0.009, 0.013, and 0.032, respectively). The multivariate analysis showed that the DDS was an independent prognostic factor of DFS (p = 0.021). Conclusion: The DDS, a simple, short-term indicator, seems to be a better surrogate endpoint than pCR, histological response and ypN0 for DFS.

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A phase II study of a modified FOLFOX6 regimen as neoadjuvant chemotherapy for locally advanced gastric cancer

Abstract: Background: We evaluated the efficacy and safety of the modified FOLFOX6 (mFOLFOX6) regimen as a neoadjuvant chemotherapy in gastric cancer patients.

Cited by 34 publications

References 42 publications

Circular RNA circHIAT1 inhibits proliferation and epithelial‐mesenchymal transition of gastric cancer cell lines through downregulation of miR‐21

Circular RNA circHIAT1 inhibits proliferation and epithelial‐mesenchymal transition of gastric cancer cell lines through downregulation of miR‐21

CapOX as neoadjuvant chemotherapy for locally advanced operable colon cancer patients: a prospective single-arm phase II trial

Downstaging depth score as a better surrogate endpoint than pCR, histological response and ypN0 for long-term outcomes in locally advanced gastric cancer patients after preoperative chemo-radiotherapy

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