A phase III trial comparing oral S-1/cisplatin and intravenous 5-fluorouracil/cisplatin in patients with untreated diffuse gastric cancer

Ajani, Jaffer A.; Abramov, Mikhail; Bondarenko, Igor; Shparyk, Y.; Gorbunova, Vera; Hontsa, A.; Otchenash, N. M.; Alsina, María; Lazarev, Sergey; Feliú, Jaime; Elme, Anneli; Esko, V.; Abdalla, Kathia Cristina; Verma, Udit; Benedetti, Fabio; Aoyama, Takafumi; Mizuguchi, Hirokazu; Makris, Lukas; Rosati, Gerardo

doi:10.1093/annonc/mdx275

Cited by 35 publications

(39 citation statements)

References 12 publications

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“…The FLAGCS [8,10], a multicenter randomized phase 3 clinical trial, also showed no difference between the 2 chemotherapies in terms of PFS (95% CI: 0.86-1.14, p = 0.92) and OS (95% CI: 0.80-1.05, p = 0.20). The other 2 RCTs (Li et al [11], Ajani et al [12]) also reported the same outcomes. Accordingly, we concluded that PS was comparable to PF in terms of OS and PFS.…”

Section: Discussionmentioning

confidence: 70%

“…After selection, 6 RCTs containing 1,736 participants (PS group: 935 participants; PF group: 801 participants) were ultimately included in our analysis ( Fig. 1) [8,[10][11][12][13][14]. Although both Ajani et al [8] and Ajani et al [10] were analyzed for the FLAGCS trial, Ajani et al [8] uniquely included outcomes of PFS, ORR, and TTF, and several AEs were provided by Ajani et al [10]; thus, both articles were included in our analysis.…”

Section: Search Resultsmentioning

confidence: 99%

“…However, which regimen is best remains controversial. We analyzed 6 high-quality RCTs, and PS and PF were compared for their anticancer effects and toxicity in the treatment of AGC [8,[10][11][12][13][14]. As the first meta-analysis comparing PS and PF, our results provided the most up-to-date medical evidence and showed that there was no significant difference between PS and PF in terms of OS, PFS, ORR, DCR, total all-grade AEs, and grade 3-4 AEs.…”

Section: Discussionmentioning

confidence: 99%

“…The First-Line Advanced Gastric Cancer Study (FLAGCS) showed no difference in efficacy between the 2 therapies (OS, p = 0.2; progression-free survival [PFS], p = 0.92; objective response rate [ORR], p = 0.40) [8] and a lower incidence of grade ≥3 adverse effects (AEs) in PS (PS vs. PF, 76.0 vs. 86.6%; p < 0.0001). However, Ajani et al [12] reported that PS has a better ORR than PF (PS vs. PF, 34.7 vs. 19.8%; p = 0.0122) but similar toxicity. Meanwhile, the study by Li et al [11] showed a lower incidence of grade ≥3 AEs in PF (PS vs. PF, 60 vs. 36%; p = 0.0015) and comparable antitumor efficacy.…”

Section: Introductionmentioning

confidence: 98%

“…However, which regimen is optimal remains unclear. To date, accumulating studies have assessed the difference between the platinum/S-1 (PS) regimen and the platinum/5-fluorouracil (PF) regimen in terms of their effect and safety in AGC [8][9][10][11][12][13][14]. The First-Line Advanced Gastric Cancer Study (FLAGCS) showed no difference in efficacy between the 2 therapies (OS, p = 0.2; progression-free survival [PFS], p = 0.92; objective response rate [ORR], p = 0.40) [8] and a lower incidence of grade ≥3 adverse effects (AEs) in PS (PS vs. PF, 76.0 vs. 86.6%; p < 0.0001).…”

Section: Introductionmentioning

confidence: 99%

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Comparison of Platinum/S-1 and Platinum/5-Fluorouracil as First-Line Chemotherapy for Advanced Gastric or Gastroesophageal Junction Cancer: A Meta-Analysis Based on Randomized Controlled Trials

et al. 2020

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Background: Platinum/S-1 (PS) and platinum/5-fluorouracil (PF) as first-line chemotherapies are extensively used for the treatment of advanced gastric or gastroesophageal junction cancer (AGC); however, there is no definite consensus on which regimen is best. In our meta-analysis, we compared PS with PF in terms of their efficacy and safety in AGC patients. Methods: PubMed, ScienceDirect, Web of Science, Scopus, Ovid MEDLINE, EMBASE, The Cochrane Library, Google Scholar, and CNKI were systematically searched for pertinent literature. We analyzed overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse effects (AEs) as major end points. Results: A total of 3,225 studies were identified, among which 6 randomized controlled trials, including 1,736 participants, were ultimately included in our analysis. Our results showed that PS and PF were comparable in terms of OS (p = 0.33, 95% confidence interval [CI]: 0.84-1.06), PFS (p = 0.63, 95% CI: 0.87-1.09), ORR (p = 0.38, 95% CI: 0.91-1.28), DCR (p = 0.41, 95% CI: 0.86-1.43), total AEs (p = 0.41, 95% CI: 0.98-1.01), and grade ≥3 AEs (p = 0.58, 95% CI: 0.82-1.41). However, those who received PF had a shorter time to failure (TTF) (p = 0.01, 95% CI: 0.77-0.97), and a significantly higher rate and more severe cases of stomatitis, nausea, and hypokalemia were reported in the PF group. Conclusions: PF and PS show similar antitumor efficacy (OS, PFS, ORR, and DCR), but patients receiving PS exhibit longer TTF and fewer AEs (stomatitis, nausea, and hypokalemia) than those receiving PF.

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Section: Discussionmentioning

confidence: 70%

Section: Search Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Comparison of Platinum/S-1 and Platinum/5-Fluorouracil as First-Line Chemotherapy for Advanced Gastric or Gastroesophageal Junction Cancer: A Meta-Analysis Based on Randomized Controlled Trials

et al. 2020

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Palliative chemotherapy and targeted therapies for esophageal and gastroesophageal junction cancer

Janmaat

Steyerberg

Gaast

et al. 2017

Cochrane Database of Systematic Reviews

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People who receive more chemotherapeutic or targeted therapeutic agents have an increased overall survival compared to people who receive less. These agents, administered as both first-line or second-line treatments, also led to better overall survival than best supportive care. With the exception of ramucirumab, it remains unclear which other individual agents cause the survival benefit. Although treatment-associated toxicities of grade 3 or more occurred more frequently in arms with an additional chemotherapy or targeted therapy agent, there is no evidence that palliative chemotherapy and/or targeted therapy decrease quality of life. Based on this meta-analysis, palliative chemotherapy and/or targeted therapy can be considered standard care for esophageal and gastroesophageal junction carcinoma.

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Histological and mutational profile of diffuse gastric cancer: current knowledge and future challenges

et al. 2021

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Gastric cancer (GC) pathogenesis is complex and heterogeneous, reflecting morphological, molecular, and genetic diversity. Diffuse gastric cancer (DGC) and intestinal gastric cancer (IGC) are the major histological types. GC may be sporadic or hereditary; sporadic GC is related to environmental and genetic low-risk factors and hereditary GC is caused by inherited high-risk mutations, so far identified only for the diffuse histotype.DGC phenotypic heterogeneity challenges the current understanding of molecular mechanisms underlying carcinogenesis. The definition of a DGC-specific mutational profile remains controversial, possibly reflecting the heterogeneity of DGC-related histological subtypes (Signet-Ring Cell Carcinoma (SRCC) and Poorly Cohesive Carcinoma not otherwise specified (PCC-NOS)). Indeed, DGC and DGC-related subtypes may present specific mutational profiles underlying the particularly aggressive behaviour and dismal prognosis of DGC vs IGC and PCC-NOS vs SRCC.In this systematic review, we revised the histological presentations, molecular classifications, and approved therapies for gastric cancer, with a focus on DGC. We then analysed results from the most relevant studies, reporting mutational analysis data specifying mutational frequencies, and their relationship with DGC and IGC histological types, and with specific DGC subtypes (SRCC and PCC-NOS). We aimed at identifying histology-associated mutational profiles with an emphasis in DGC and its subtypes (DGC vs IGC; sporadic vs hereditary DGC; and SRCC vs PCC-NOS). We further used these mutational profiles to identify the most commonly affected molecular pathways and biological functions, and explored the clinical trials directed specifically to patients with DGC. This systematic analysis is expected to expose a DGC-specific molecular profile and shed light into potential targets for therapeutic intervention, which are currently missing.

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A phase III trial comparing oral S-1/cisplatin and intravenous 5-fluorouracil/cisplatin in patients with untreated diffuse gastric cancer

Abstract: NCT01285557.

Cited by 35 publications

References 12 publications

Comparison of Platinum/S-1 and Platinum/5-Fluorouracil as First-Line Chemotherapy for Advanced Gastric or Gastroesophageal Junction Cancer: A Meta-Analysis Based on Randomized Controlled Trials

Comparison of Platinum/S-1 and Platinum/5-Fluorouracil as First-Line Chemotherapy for Advanced Gastric or Gastroesophageal Junction Cancer: A Meta-Analysis Based on Randomized Controlled Trials

Palliative chemotherapy and targeted therapies for esophageal and gastroesophageal junction cancer

Histological and mutational profile of diffuse gastric cancer: current knowledge and future challenges

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