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Chemotherapy in Advanced Gastric Cancer: A Systematic Review and Meta-Analysis Based on Aggregate Data
Open accessAbstract
Purpose: This systematic review and meta-analysis were performed to assess the efficacy and tolerability of chemotherapy in patients with advanced gastric cancer. Methods: Randomized phase II and III clinical trials on first-line chemotherapy in advanced gastric cancer were identified by electronic searches of Medline, Embase, the Cochrane Controlled Trials Register, and Cancerlit; hand searches of relevant abstract books and reference lists; and contact to experts. Meta-analysis was performed using the fixed-effect model. Overall survival, reported as hazard ratio (HR) with 95% CI, was the primary outcome measure. Results: Analysis of chemotherapy versus best supportive care (HR = 0.39; 95% CI, 0.28 to 0.52) and combination versus single agent, mainly fluorouracil (FU) -based chemotherapy (HR = 0.83; 95% CI = 0.74 to 0.93) showed significant overall survival benefits in favor of chemotherapy and combination chemotherapy, respectively. In addition, comparisons of FU/cisplatin-containing regimens with versus without anthracyclines (HR = 0.77; 95% CI, 0.62 to 0.95) and FU/anthracycline-containing combinations with versus without cisplatin (HR = 0.83; 95% CI, 0.76 to 0.91) both demonstrated a significant survival benefit for the three-drug combination. Comparing irinotecan-containing versus nonirinotecan-containing combinations (mainly FU/cisplatin) resulted in a nonsignificant survival benefit in favor of the irinotecan-containing regimens (HR = 0.88; 95% CI, 0.73 to 1.06), but they have never been compared against a three-drug combination. Conclusion: Best survival results are achieved with three-drug regimens containing FU, an anthracycline, and cisplatin. Among these, regimens including FU as bolus exhibit a higher rate of toxic deaths than regimens using a continuous infusion of FU, such as epirubicin, cisplatin, and continuous-infusion FU.
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“The pyrimidine analogue 5-fluorouracil (5-FU) is a synthetic analogue of uracil that inhibits thymidylate synthase, limiting the availability of thymidine nucleotides for DNA synthesis (Figure 1b, Figure 2c). 5-FU and the related 5-FU-prodrug capecitabine remain widely used chemotherapies today and are an important treatment for gastrointestinal cancers (Heidelberger et al., 1957; Wagner et al., 2”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Wagner et al., 2006
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“Randomized trials in Western countries have demonstrated higher response rates and survival benefi ts with a regimen of epirubicin, cisplatin, and infused fl uorouracil (ECF) [63, 64], and the effi cacy of this regimen has also been confi rmed by a meta-analysis [65].”
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“Development of treatment strategies to prevent locoregional and systemic recurrences is the main goal of current research [13, 16, 17].”
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“Fluoropyrimidines are essential in the treatment of gastric and colorectal cancer in advanced stages and have shown survival benefit compared with the best supportive care (1, 2).”
Manu, K. A., Shanmugam, M. K., Ramachandran, L., Li, F., Fong, C. W., Kumar, A. P., Tan, P. B. O., & Sethi, G. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-2470 · Cited by 146
“Chemotherapy constitutes an important treatment regimen for gastric cancers besides surgical resection (3).”
BackgroundPinto, C., Fabio, F. D., Barone, C. A., Siena, S., Falcone, A., Cascinu, S., Llimpe, F. L. R., Stella, G. M., Schinzari, G., Artale, S. A., et al. (2009) · British Journal of Cancer · doi:10.1038/sj.bjc.6605319 · Cited by 141
“In addition, combination chemotherapy regimens containing 5-fluorouracil, anthracycline, and cisplatin were associated with a significant survival benefit when compared with 5-fluorouracil and anthracycline regimens without cisplatin (HR, 0.83; 95% CI, 0.76–0.91) (Wagner et al, 2006).”
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“Systemic chemotherapy is the only effective treatment available in these situations, but it has extremely poor results and the median survival time is invariably shorter than 1 year [4–6].”
BackgroundChemotherapy of advanced gastric cancer
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Ginger ingredients reduce viability of gastric cancer cells via distinct mechanisms
Ishiguro, K., Ando, T., Maeda, O., Ohmiya, N., Niwa, Y., Kadomatsu, K., & Goto, H. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.08.012 · Cited by 138
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“…limitations: (1) a small, approximately 1-month, survival advantage observed in the meta-analysis was achieved at the expense of increased toxicity (Wagner et al, 2006); (2) chemotherapy-related toxicities, such as neutropenia, anaemia, stomatitis and diarrhoea, occurred more frequently in the…”
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“While current fluorouracil- and cisplatin-based combination chemotherapy regimens confer a survival benefit when compared to best supportive care [2], outcomes remain suboptimal.”
Moehler, M. H., Mueller, A., Trarbach, T., Lordick, F., Seufferlein, T. T. W., Kubicka, S., Geißler, M., Schwarz, S., Galle, P. R., & Kanzler, S. (2010) · Annals of Oncology · doi:10.1093/annonc/mdq591 · Cited by 124
“Many chemotherapeutic agents have shown activity in advanced GC and, currently, cisplatin/ 5-fluorouracil (5-FU)-based chemotherapeutic regimens are the mainstay of treatment of patients with metastatic disease [3].”
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Surgical treatment for peritoneal carcinomatosis from gastric cancer
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“In terms of first-line regimens, a combination of fluoropyrimidine and platinum is regarded as a standard option as this combination has shown superior clinical outcomes in phase III trials when compared with fluoropyrimidine monotherapy and other combinations (Wagner et al, 2006).”
ResultMicroRNAs as potential biomarkers for gastric cancer
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“In the metastatic disease setting, palliative chemotherapy improves survival compared with supportive care alone, with combined drug therapy yielding the best results [1–3].”
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Exosome-Delivered c-Met siRNA Could Reverse Chemoresistance to Cisplatin in Gastric Cancer
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“The five-year survival rate for advanced or metastatic gastric cancer is only 5–20%, with a median overall survival of less than 1 year [3, 4].”
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“At this advanced stage, gastric cancer is largely incurable [2,3].”
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“In these patients, a combination chemotherapy exhibits improved overall survival compared with a single-agent chemotherapy or best supportive care [5].”
Second-line chemotherapy for patients with advanced gastric cancer: who may benefit?
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“Unfortunately, the benefits of combination chemotherapy have been modest (Wagner et al, 2006).”
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“Many clinical trials have shown the effectiveness of chemotherapy in unresectable gastric cancer (Wöhrer et al. 2004; Wagner et al. 2006; Rivera et al. 2007).”
BackgroundAn Analytics Approach to Designing Combination Chemotherapy Regimens for Cancer
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“…for a number of cancers have demonstrated efficacy gains of combination chemotherapy regimens over single-agent treatments (Delbaldo et al. 2004, Wagner 2006), and in this work we found that 80% of all chemotherapy clinical trials for advanced gastric cancer have tested multidrug treatments.”
Background
Metadata
- Authors
- Wagner, A. D., Grothe, W., Haerting, J., Kleber, G., Grothey, A., & Fleig, W. E.
- Affiliations
- From the First Department of Medicine, Coordinating Centre for Clinical Trials, Department of Medicine IV, and Institute of Medical Epidemiology, Biostatistics and Informatics, Martin-Luther-University Halle-Wittenberg, Halle/Saale, Germany; and Mayo Clinic College of Medicine, Rochester, MN
- Mayo Clinic (US)
- Venue
- Journal of Clinical Oncology
- Published
- 2006-06-20
- Volume
- 24
- Issue
- 18
- Pages
- 2903-2909
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2145390243
- Cited by
- 1,171
- References
- 51
- Citations by year
- 2026: 7 · 2025: 15 · 2024: 26 · 2023: 28 · 2022: 34 · 2021: 64 · 2020: 55 · 2019: 54 · 2018: 69 · 2017: 89 · 2016: 72 · 2015: 84 · 2014: 105 · 2013: 92 · 2012: 77
- FWCI
- 9.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Society of Clinical Oncology
- Bundesministerium für Bildung und Forschung (01GH0105)
- Topics
- Health Sciences › Medicine › Oncology › Gastric Cancer Management and Outcomes
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Surgery › Intraperitoneal and Appendiceal Malignancies
- Keywords
- advanced gastric cancer, first-line chemotherapy, 5-fluorouracil, cisplatin, anthracyclines, irinotecan, combination chemotherapy, overall survival, best supportive care, epirubicin, chemotherapy toxicity
- MeSH terms
- Antineoplastic Combined Chemotherapy Protocols, Humans, Stomach Neoplasms
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