Progress of Individualized Chemotherapy for Gastric Carcinoma Under the Guidance of Genetic Testing

Background: Gastric cancer is a major malignancy that has high incidence rates worldwide. Approximately 30% of patients with gastric cancer have progressed into advanced stages at the time of diagnosis. Chemotherapy is the standard-of-care for most advanced gastric cancer and elicits variable responses among patients. Personalized chemotherapy based on genetic information of individual patients with gastric cancer has gained increasing attention among oncologists for guiding chemotherapeutic regimens. Methods: This review summarizes recent progress of individualized chemotherapy in gastric cancer guided by pharmacogenomics. Variable medical research search engines, such as PubMed, Google Scholar, SpringerLink and ScienceDirect, were used to retrieve related literature. Only peerreviewed journal articles were selected for further analyses. Results and Conclusion: The efficiency of chemotherapy in patients with gastric cancer is not only determined by chemotherapeutic drugs but is also directly and indirectly influenced by functionally correlative genes. Individual gene alteration or polymorphism remarkably affects patients’ responses to particular chemotherapy. Most studies have focused on the influence of single-gene alteration on a selected drug, and only a few works explored the interaction between therapeutics and a panel of genes. Individualized chemotherapy regimens guided by a genetic survey of a multiple-gene panel are expected to remarkably improve the treatment efficacy in patients with advanced gastric cancer and may become the new standard for personalizing chemotherapy for gastric cancer in the near future.

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Correlation between MEK signature and Ras gene alteration in advanced gastric cancer

Oncotarget ◽

10.18632/oncotarget.18182 ◽

2017 ◽

Vol 8 (64) ◽

pp. 107492-107499 ◽

Cited By ~ 4

Author(s):

Soomin Ahn ◽

Roz Brant ◽

Alan Sharpe ◽

Jonathan R. Dry ◽

Darren R. Hodgson ◽

...

Keyword(s):

Gastric Cancer ◽

Advanced Gastric Cancer ◽

Ras Gene ◽

Gene Alteration

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Recent Advances in the Diagnosis, Staging, Treatment, and Prognosis of Advanced Gastric Cancer: A Literature Review

Frontiers in Medicine ◽

10.3389/fmed.2021.744839 ◽

2021 ◽

Vol 8 ◽

Author(s):

Zhi-da Chen ◽

Peng-fei Zhang ◽

Hong-qing Xi ◽

Bo Wei ◽

Lin Chen ◽

...

Keyword(s):

Gastric Cancer ◽

Neoadjuvant Chemotherapy ◽

Advanced Gastric Cancer ◽

Malignant Tumors ◽

Treatment Options ◽

Survival Rates ◽

Radical Resection ◽

Recent Advances ◽

Drug Choice ◽

Advanced Stages

Gastric cancer is one of the most common cause of cancer related deaths worldwide which results in malignant tumors in the digestive tract. The only radical treatment option available is surgical resection. Recently, the implementation of neoadjuvant chemotherapy resulted in 5-year survival rates of 95% for early gastric cancer. The main reason of treatment failure is that early diagnosis is minimal, with many patients presenting advanced stages. Hence, the greatest benefit of radical resection is missed. Consequently, the main therapeutic approach for advanced gastric cancer is combined surgery with neoadjuvant chemotherapy, targeted therapy, or immunotherapy. In this review, we will discuss the various treatment options for advanced gastric cancer. Clinical practice and clinical research is the most practical way of reaching new advents in terms of patients' characteristics, optimum drug choice, and better prognosis. With the recent advances in gastric cancer diagnosis, staging, treatment, and prognosis, we are evident that the improvement of survival in this patient population is just a matter of time.

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A Rare Case of Severe Lactic Acidosis from 5-Fluorouracil after mFOLFOX6 Treatment in a Patient with Advanced Gastric Cancer

Case Reports in Oncology ◽

10.1159/000514296 ◽

2021 ◽

pp. 545-549

Author(s):

Tae Hoon Lee ◽

Dan Le

Keyword(s):

Gastric Cancer ◽

Lactic Acidosis ◽

Advanced Gastric Cancer ◽

Palliative Chemotherapy ◽

Standard Of Care ◽

Type B ◽

Chemotherapy Treatment ◽

Life Threatening ◽

First Time ◽

Therapy Treatment

Gastric cancer is one of the most common cancers worldwide and is one of the deadliest types of neoplasm. Many patients present with an advanced stage where palliative chemotherapy is the standard of care. 5-Fluorouracil (5-FU) remains the backbone of systemic therapy treatment in advanced gastric cancer, although is associated with many side effects. While cases of encephalopathy caused by hyperammonemia have been reported, lactic acidosis after systemic 5-FU exposure is exceedingly rare. We present here for the first time a case of type B lactic acidosis secondary to mFOLFOX6 therapy in advanced gastric cancer. This patient presented with acute delirium, dystonia, and a lactate of 11.7 mmol/L, which peaked to 18.7 mmol/L, within 48 h of chemotherapy treatment. Routine clinical monitoring of lactate may be beneficial to avoid this potentially life-threatening adverse event.

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Chemotherapy for advanced gastric cancer: across the years for a standard of care

Expert Opinion on Pharmacotherapy ◽

10.1517/14656566.8.6.797 ◽

2007 ◽

Vol 8 (6) ◽

pp. 797-808 ◽

Cited By ~ 32

Author(s):

Mario Scartozzi ◽

Eva Galizia ◽

Lorena Verdecchia ◽

Rossana Berardi ◽

Stefania Antognoli ◽

...

Keyword(s):

Gastric Cancer ◽

Advanced Gastric Cancer ◽

Standard Of Care

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Retrospective analysis for efficacy and safety of nivolumab in advanced gastric cancer patients (pts) with malignant ascites.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.392 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 392-392

Author(s):

Akinori Sugaya ◽

Shunsuke Ueyama ◽

Hirosumi Suzuki ◽

Takeshi Yamada ◽

Yoshiyuki Yamamoto ◽

...

Keyword(s):

Gastric Cancer ◽

Advanced Gastric Cancer ◽

Performance Status ◽

Progression Free Survival ◽

Poor Performance ◽

Standard Of Care ◽

Malignant Ascites ◽

Poor Performance Status ◽

Efficacy And Safety ◽

Neutrophil Lymphocyte Ratio

392 Background: Nivolumab is a standard of care as the later-line therapy for advanced gastric cancer. However, there are few data about efficacy and safety of nivolumab for pts with malignant ascites. Methods: We conducted a multicenter retrospective study for pts with advanced gastric cancer who received nivolumab alone from Oct. 2017 to Feb. 2019. Pts were divided into two groups; high ascites burden (HAB) with moderate or massive ascites and non-HAB with none or a small amount of localized ascites at pelvis and/or liver surface. Results: A total of 72 pts (23 pts with HAB and 49 pts with non-HAB) were evaluable. The HAB group had more pts with young (median 62 vs 70 years), female (35 vs 14 %), no prior gastrectomy (63 vs 35 %) and poor performance status (PS > 1; 26 vs 10 %), compared to the non-HAB group. Disease control rate was 44% (95% CI 23-64%) in the HAB group and 57% (95% CI 43-71%) in the non-HAB group. Ascites decreased in 4 pts (17%) and completely disappeared in 2 pts (8.7%) in the HAB group. These 6 pts were all male and had prior ramucirumab treatment with a mean neutrophil-lymphocyte ratio 2.1 (from 0.85 to 3.7) at the initiation of nivolumab. After 5 months of follow up period, disease progression or death events for progression-free survival (PFS) occurred in 74% of the HAB group and 53% of the non-HAB group. Median PFS was 1.0 (95%CI 0.5-1.5) and 2.6 (95%CI 0.9-7.4) months in pts with HAB and non-HAB, respectively. PFS rates at 6 months were 31% in the HAB group and 33% in the non-HAB group. Immune-related adverse events occurred in 26% of the HAB group and 16% of the non-HAB group including one and two pts with grade 3 or 4 events, respectively. There was no treatment-related death in both groups. Conclusions: Although pts with HAB showed trends of worse outcomes compared with those with non-HAB, nivolumab was suggested to provide a survival benefit to some pts with HAB, and was tolerable in the HAB group.

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Gastric cancer with pregnancy: two case reports

Obstetric Medicine ◽

10.1258/om.2011.110035 ◽

2011 ◽

Vol 4 (3) ◽

pp. 125-126 ◽

Cited By ~ 1

Author(s):

Sahar Mohamed ◽

Seema Chakravarti

Keyword(s):

Gastric Cancer ◽

Rare Disease ◽

Advanced Gastric Cancer ◽

Poor Prognosis ◽

Case Reports ◽

Early Endoscopy ◽

Advanced Stages

Gastric cancer with pregnancy is quite rare, and is often diagnosed at advanced stages with poor prognosis. This highlights the need to improve diagnosis by means of early endoscopy. We herein report two cases of advanced gastric cancer during pregnancy who sadly died within five weeks of diagnosis, to alert clinicians to this rare disease.

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A phase II study (KSCC/HGCSG/CCOG/PerSeUS1501B) of trastuzumab plus S-1 and oxaliplatin for HER2-positive advanced gastric cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.4059 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 4059-4059 ◽

Cited By ~ 2

Author(s):

Katsunori Shinozaki ◽

Satoshi Yuki ◽

Tomomi Kashiwada ◽

Tetsuya Kusumoto ◽

Masaaki Iwatsuki ◽

...

Keyword(s):

Gastric Cancer ◽

Adverse Events ◽

Advanced Gastric Cancer ◽

Phase Ii ◽

Response Rate ◽

Incidence Rates ◽

Phase Iii ◽

Efficacy And Safety ◽

Her2 Positive ◽

Standard Regimen

4059 Background: A combination of S-1 and cisplatin (SP) has been the standard regimen for advanced gastric cancer (AGC) in East Asia. The combination of S-1 and oxaliplatin (SOX100) was demonstrated to be non-inferior to SP in the randomized phase III study. The ToGA study demonstrated that trastuzumab (T-mab) combination therapies with cisplatin and fluoropyrimidines improved the overall survival of patients with HER2-positive AGC. This multicenter study is the first phase II trial to assess the efficacy and safety of T-mab in combination with S-1 and oxaliplatin (HER-SOX130) in HER2-positive AGC. Methods: Patients with HER2-positive AGC or recurrent gastric cancer defined to be IHC 3+ or IHC 2+/FISH positive received 80 mg/m2 S-1 per day orally on days 1–14, 130 mg/m2 oxaliplatin intravenously on day 1, and T-mab (8-mg/kg loading dose and 6 mg/kg thereafter) intravenously on day 1 of a 21-day cycle until one of the criteria for withdrawal of the study treatment occurred. The primary end-point was the response rate (RR). Adverse events were recorded based on the NCI-CTCAE Vers.4.0. The threshold response rate was defined as 50%, and the expected rate was set at 70%, with an 80% power and a 1-sided alpha value of 0.05. The calculated sample size was 37 patients. Results: For this study, 42 patients (median age, 66 years) were enrolled from June 2015 to May 2016. Three patients were excluded owing to ineligibility. Efficacy and safety analyses were conducted in the full analysis set of 39 patients. The proportion of patients with IHC 3+ was 87%. The confirmed RR assessed by the independent review committee was 82.1(32/39) % (95% confidence interval [CI]: 67.3–91.0), and the disease control rate was 87.2(34/39) % (95% CI: 73.3–94.4). The incidence rates of grade 3 or 4 adverse events were as follows: neutropenia, 12.8%; thrombocytopenia, 17.9%; anemia, 10.3%; sensory neuropathy, 5.1%; anorexia, 17.9%; diarrhea, 7.7%; and teary eyes, 2.6%. Conclusions: HER-SOX130 demonstrated encouraging efficacy with a favorable safety profile. The survival benefit of this regimen needs to be validated by conducting further follow-up of patients. Clinical trial information: 000017552.

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