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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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BackgroundGastric Cancer: Advanced/Metastatic Disease
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Nishikawa, K., Kawakami, H., Shimokawa, T., Fujitani, K., Tamura, S., Endo, S., Kobayashi, M., Kawada, J., Kurokawa, Y., Tsuburaya, A., et al. (2023) · International Journal of Clinical Oncology · doi:10.1007/s10147-023-02402-1 · Cited by 1
“Combination chemotherapy regimens provide better response rates (RRs) and modest survival benefits compared with single-agent therapies [2].”
BackgroundChemotherapy Efficacy and Tolerability in Metastatic Gastric Cancer Patients Aged 75 Years and Older
Sezigin, Y. (2023) · Eurasian Journal of Medical Investigation · doi:10.14744/ejmi.2023.71797 · Cited by 1
“[13] In our study, OS was 8.6 months in those receiving combination therapy and 7.9 months in those receiving monotherapy, and there was no statistically significant difference.”
InfluentialApplication of Artificial Intelligence in Gastric Cancer
Lee, J.-I. (2023) · Journal of Digestive Cancer Research · doi:10.52927/jdcr.2023.11.3.130 · Cited by 1
Ikejiri, F., Yokomizo, K., & Tamura, K. (2024) · Oncology Letters · doi:10.3892/ol.2024.14404 · Cited by 1
Chaudhuri, T., Bankira, J., Upadhyay, A. K., Panda, R., Pandey, V., Mitra, S., & Mukherjee, S. (2024) · South Asian Journal of Cancer · doi:10.1055/s-0044-1791524 · Cited by 1
“14 But later on, in a randomized phase II study including Asian patients, the addition ofepirubicin to a PF combination failed to improve response rate or survival.”
Clinical Use of Cisplatin Liposomes for Patients With Refractory Advanced Cancer
Komura, Y., Kimura, S., Katagiri, T., Hirasawa, Y., Hirayama, M., Okuda, T., Muranishi, H., & Homma, K. (2024) · Cureus · doi:10.7759/cureus.73181
Shah, M., Prasad, A., Rajan, D., Tan, C. B., Shah, M. R., Raghavan, P., & Mustacchia, P. J. (2012) · Case Reports in Medicine · doi:10.1155/2012/651232 · Cited by 1
“Randomized trials on combined chemotherapy agents, such as, cisplatin along with bleomycin or etoposide have demonstrated statistically significant improved survival rates over single chemotherapy agents [8, 9].”
Systemic therapy for advanced gastric cancer: a review
Kelsen, D. P. (2007) · Hematology/Oncology Clinics of North America · doi:10.1016/s0889-8588(07)80006-2 · Cited by 1
Giuliani, F., Romito, S., Maiello, E., Capobianco, A. M. L., Carrozza, F., Nugnes, I., Misino, A., Valerio, M. R., Manzione, L., & Colucci, G. (2008) · European Journal of Cancer Supplements · doi:10.1016/j.ejcsup.2008.06.017 · Cited by 1
Pharmacology of Aging and Cancer: How Useful Are Pharmacokinetic Tests?
Lichtman, S. M. (2013) · Interdisciplinary topics in gerontology and geriatrics · doi:10.1159/000343618 · Cited by 1
Brown, J., Liepa, A. M., Bapat, B., Madhwani, S., Lorenzen, S., García‐Foncillas, J., Candrilli, S. D., & Kaye, J. A. (2019) · European Journal of Cancer Care · doi:10.1111/ecc.13213 · Cited by 1
Impact of Oxaliplatin-Induced Neuropathy on Subsequent Paclitaxel for Advanced Gastric Cancer
Sato, J., Iwasa, S., Honma, Y., Takashima, A., Okita, N. T., Kato, K., Hamaguchi, T., Yamada, Y., & Boku, N. (2020) · International Journal of Clinical Medicine · doi:10.4236/ijcm.2020.119045 · Cited by 1
Role of Specific Phytochemicals Against Gastrointestinal Malignancies
Dariya, B., Merchant, N., & Nagaraju, G. P. (2020) · Springer eBooks · doi:10.1007/978-3-030-48405-7_1 · Cited by 1
Mamdani, H. M., & Jalal, S. I. (2021) · American Society of Clinical Oncology Educational Book · doi:10.1200/edbk_321243 · Cited by 2
Li, W., Tang, Y., Wang, D., & Li, J. (2023) · All Life · doi:10.1080/26895293.2023.2288532 · Cited by 1
Multimodality Therapy in Gastric Cancer
Malhotra, U., & Fong, M. K. (2014) · Springer eBooks · doi:10.1007/978-3-319-09342-0_9 · Cited by 1
“conducted a meta-analysis regarding the effects of chemotherapy on advanced gastric cancer and showed that the combination of chemotherapy agents improved overall survival by 17 % [ 24 ].”
BackgroundInfluentialMöglichkeiten der systemischen Therapie in metastasierten Stadien des Magenkarzinoms
Wagner, D., & Stahl, M. (2008) · Der Onkologe · doi:10.1007/s00761-008-1338-9 · Cited by 1
New horizons for gastric cancer: commentary
Macdonald, J. S., & Cervantes, A. M. R. (2006) · European Journal of Cancer Supplements · doi:10.1016/s1359-6349(06)70001-5 · Cited by 1
Upper Gastrointestinal Malignancies: A New Era in Clinical Colorectal Cancer
Hawkes, E. A., Chau, I., Ilson, D. H., & Cunningham, D. (2009) · Clinical Colorectal Cancer · doi:10.3816/ccc.2009.n.030 · Cited by 1
Phase II study of oxaliplatin, UFT, and leucovorin in patients with metastatic gastric cancer
Siemerink, E., Drenth, A. F. J., Mulder, N. H., Plukker, J. T. M., & Hospers, G. A. P. (2010) · Gastric Cancer · doi:10.1007/s10120-010-0545-4 · Cited by 1
Drug Development in Advanced Esophagogastric Cancer: The Art of Extrapolation
Punt, C. J. A. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2010.30.4923 · Cited by 1
Analytics for Improved Cancer Screening and Treatment
Silberholz, J. (2015) · DSpace@MIT (Massachusetts Institute of Technology) · Cited by 1
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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