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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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“The median survival of patients with advanced gastric cancer (AGC) is 7–10 months in a majority of large clinical studies [2].”
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Increased survival associated with surgery and radiation therapy in metastatic gastric cancer
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“However, most gastric cancers are diagnosed at advanced or metastatic stages when the tumor is considered unresectable.(3) Several phase 3 randomized control trials of various chemotherapy regimens in metastatic gastric cancer have shownmedian survivals ranging from 7.”
BackgroundAggressive Locoregional Surgical Therapy for Gastric Peritoneal Carcinomatosis
Magge, D. R., Zenati, M. S., Mavanur, A. A., Winer, J. H., Ramalingam, L., Jones, H., Zureikat, A. H., Holtzman, M. P., Lee, K., Ahrendt, S. A., et al. (2013) · Annals of Surgical Oncology · doi:10.1245/s10434-013-3327-5 · Cited by 58
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Docetaxel, Cisplatin, and Fluorouracil in Gastric Cancer: Does the Punishment Fit the Crime?
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Dihydropyrimidinase-like 3 facilitates malignant behavior of gastric cancer
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“For patients with metastatic disease, systemic chemotherapy is the most effective treatment modality and could adequately palliate the symptoms of gastric cancer [2].”
BackgroundPredictive Biomarkers of Immune Checkpoint Inhibition in Gastroesophageal Cancers
Sundar, R., Smyth, E. C., Peng, S., Yeong, J. P.-S., & Tan, P. B. O. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.00763 · Cited by 55
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“Although meta-analysis of the results in gastric and gastroesophageal junction cancer suggests the possibility of a modest survival advantage from the addition of chemotherapy to best supportive care, the overall treatment results remain disappointing [8].”
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“Furthermore, a recent meta-analysis concluded that the best survival results are achieved with regimens containing anthracyclines, cisplatin and 5FU and among these ECF was the most well-tolerated (Wagner et al, 2006).”
Polysaccharides from Rhizopus nigricans mycelia induced apoptosis and G2/M arrest in BGC-823 cells
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“However, GC usually shows resistance to chemotherapeutics which exhibit a relatively short control of this disease and correlated symptoms, and the survival of most of these patients is less than one year [9, 10].”
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“The average five‐year survival rate for gastric cancer is <10% (3).”
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“However, since cisplatin-containing regimens are associated with high rates of toxicity in gastric cancer [4], platinum-free frontline treatment alternatives are sought.”
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“Several combination chemotherapy regimens have been developed as fi rst-line therapies over the past decade, with responses ranging from 20% to 40%; nevertheless, median OS remains very poor, being just 7–10 months [4].”
BackgroundTargeted therapies in gastroesophageal cancer
Kasper, S., & Schüler, M. (2014) · European Journal of Cancer · doi:10.1016/j.ejca.2014.01.009 · Cited by 53
“Palliative chemotherapy prolongs survival and improves cancer-related symptoms in these patients as well as in patients with primary metastatic disease [86].”
BackgroundIdentification of prognostic factors and surgical indications for metastatic gastric cancer
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“therapy over best supportive care in patients with metastatic or inoperable disease, 5-year survival remains at 5–20% [3].”
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Gastric cancer: current and evolving treatment landscape
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“Unfortunately, the disease often exhibits and develops resistance to chemotherapeutic agents with a relatively short period of disease and symptom control, and most patients would die within 1 year [5, 6].”
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“Triplet chemotherapy is more active than singlet or doublet chemotherapy in terms of response rates, but is not routinely used in a palliative setting because of its higher toxicities [14].”
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“A number of trials have justified the use of palliative chemotherapy as compared to best supportive care to improve patient survival [4].”
BackgroundMethodmiR-21 Is a Promising Novel Biomarker for Lymph Node Metastasis in Patients with Gastric Cancer
Xu, Y., Sun, J., Xu, J., Li, Q., Guo, Y.-W., & Zhang, Q. (2012) · Gastroenterology Research and Practice · doi:10.1155/2012/640168 · Cited by 54
“Five-year survival rate for advanced or metastatic gastric cancer is nearly 5–20%, with median overall survival being less than 1 year [3, 4].”
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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