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      News & Perspective Drugs & Diseases CME & Education Academy Video Decision Point
      Drugs & Diseases > Oncology

      Gastric Cancer Medication

      Updated: Apr 20, 2021
      • Author: Elwyn C Cabebe, MD; Chief Editor: N Joseph Espat, MD, MS, FACS  more...
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      Medication

      Medication Summary

      The goals of pharmacotherapy are to induce remission, reduce morbidity, and prevent complications.

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      Antineoplastics, Antimetabolite

      Class Summary

      Antineoplastic agents inhibit cell growth and proliferation.

      Fluorouracil (Adrucil)

      Fluoropyrimidine analog. Cell cycle-specific with activity in the S-phase as single agent and has for many years been combined with biochemical modulator leucovorin.Has activity as single agent that inhibits DNA replication and transcription. Cytotoxicity is cell-cycle nonspecific. Shown to be effective in adjuvant setting. Classic antimetabolite anticancer drug with chemical structure similar to endogenous intermediates or building blocks of DNA or RNA synthesis. 5-FU inhibits tumor cell growth through at least 3 different mechanisms that ultimately disrupt DNA synthesis or cellular viability. These effects depend on intracellular conversion of 5-FU into 5-FdUMP, 5-FUTP, and 5-FdUTP. 5-FdUMP inhibits thymidylate synthase (key enzyme in DNA synthesis), which leads to accumulation of dUMP, which then gets misincorporated into the DNA in the form of 5-FdUTP resulting in inhibition of DNA synthesis and function with cytotoxic DNA strandbreaks. 5-FUTP is incorporated into RNA and interferes with RNA processing.

      Capecitabine (Xeloda)

      Fluoropyrimidine carbamate prodrug of 5-fluorouracil (5-FU). Capecitabine itself is inactive. Undergoes hydrolysis in liver and tissues to form the active moiety (fluorouracil), inhibiting thymidylate synthetase, which in turn blocks methylation of deoxyuridylic acid to thymidylic acid. This step interferes with DNA and to a lesser degree with RNA synthesis.

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      Antineoplastics, Platinum Analog

      Class Summary

      Platinum compounds inhibit cell growth and proliferation.

      Carboplatin

      Analog of cisplatin. This is a heavy metal coordination complex that exerts its cytotoxic effect by platination of DNA, a mechanism analogous to alkylation, leading to interstrand and intrastrand DNA crosslinks and inhibition of DNA replication. Binds to protein and other compounds containing SH group. Cytotoxicity can occur at any stage of the cell cycle, but cell is most vulnerable to action of these drugs in G1 and S phase.

      Cisplatin

      Cisplatin is a platinum-containing compound that exerts an antineoplastic effect by covalently binding to DNA, with preferential binding to N-7 position of guanine and adenosine. It can react with 2 different sites on DNA to produce cross-links. The platinum complex also can bind to nucleus and cytoplasmic protein.

      Oxaliplatin (Eloxatin)

      Cisplatin is a platinum-containing compound that exerts an antineoplastic effect by covalently binding to DNA, with preferential binding to N-7 position of guanine and adenosine. It can react with 2 different sites on DNA to produce cross-links. The platinum complex also can bind to nucleus and cytoplasmic protein.

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      Antineoplastics, Anthracycline

      Class Summary

      Anthracyclines inhibit cell growth and proliferation.

      Epirubicin (Ellence)

      Doxorubicin is an anthracycline antibiotic that inhibits DNA and RNA synthesis. It acts throughout the entire cell cycle and by direct intercalating into DNA triggers DNA breakage by topoisomerase II, causing subsequent cytocydal activity.

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      Antineoplastics, Topoisomerase Inhibitors

      Class Summary

      Topoisomerase inhibitors inhibit cell growth and proliferation.

      Irinotecan (Camptosar)

      Semisynthetic derivative of camptothecin, an alkaloid extract from the Camptotheca acuminate tree. Inactive in its parent form. Converted by the carboxylesterase enzyme to its active metabolite from, SN-38. SN-38 binds to and stabilizes the topoisomerase I-DNA complex and prevents the relegation of DNA after it has been cleaved by topoisomerase I, inhibiting DNA replication.

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      Antineoplastics, Antimicrotubular (Taxanes)

      Class Summary

      Antimicrotubular agents inhibit cell growth and proliferation.

      Paclitaxel

      Taxanes alone or in combination with other agents have demonstrated efficacy in the treatment of hormone-refractory prostate cancer. Mechanisms of action are tubulin polymerization and microtubule stabilization.

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      Antineoplastics, Anti-HER2

      Class Summary

      Monoclonal antibodies are a form of drug delivery that specifically targets the tumor cells, thus reducing the systemic side effects of chemotherapy and at the same time being more effective than routine forms of chemotherapy agents.

      Trastuzumab (Herceptin)

      Trastuzumab is a monoclonal antibody that binds to the human epidermal growth factor receptor 2 protein (HER-2) extracellular domain. It inhibits the proliferation of cells overexpressing HER-2 protein.

      Trastuzumab deruxtecan (Enhertu, Fam-trastuzumab deruxtecan-nxki)

      This conjugate comprises trastuzumab, a humanized anti-HER2 monoclonal antibody, attached to deruxteca, which is composed of a cleavable linker and topoisomerase inhibitor (DXd). The drug binds to HER2 on tumors and undergoes internalization and intracellular linker cleavage by lysosomal enzymes. Upon release, DXd causes DNA damage and apoptotic cell death. It is approved for locally advanced and metastatic HER2-positive gastric or GE junction adenocarcinoma in patients who were previously treated with a trastuzumab-based regimen.

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      Antineoplastics, VEGF Inhibitor

      Class Summary

      Vascular endothelial growth factor inhibitors reduce tumor vascularity and growth.

      Ramucirumab (Cyramza)

      Ramucirumab is a monoclonal antibody that inhibits activation of vascular endothelial growth factor receptor 2 (VEGFR2). Has high affinity for VEGFR2 binding and blocks binding of VEFGR ligands, VEGF-A, VEGF-C and VEGF-D.  

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      PD-1/PD-L1 Inhibitors

      Class Summary

      PD-1 and related target PD-ligand 1 (PD-L1) are expressed on the surface of activated T cells under normal conditions. PD-L1/PD-1 interaction inhibits immune activation and reduces T-cell cytotoxic activity when bound.

      Nivolumab (Opdivo)

      Indicated in combination with fluoropyrimidine- and platinum-containing chemotherapy as first-line treatment for advanced or metastatic gastric cancer, gastroesophageal junction cancer, or esophageal adenocarcinoma. 

      Pembrolizumab (Keytruda)

      Indicated in combination with fluoropyrimidine- and platinum-containing chemotherapy as first-line treatment for advanced or metastatic gastric cancer, gastroesophageal junction cancer, or esophageal adenocarcinoma that is not amenable to surgical resection or definitive chemoradiation. Also indicated as a single agent for recurrent, locally advanced or metastatic, squamous cell carcinoma of the esophagus (ESCC) whose tumors express programmed death ligand 1 (PD-L1) with a Combined Positive Score (CPS) 10 or greater, as determined by an FDA-approved test, with disease progression after 1 or more prior lines of systemic therapy.

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      Thymidine Analog

      Class Summary

      Following uptake into cancer cells, trifluridine is incorporated into DNA, interferes with DNA synthesis and inhibits cell proliferation.

      Tipiracil/trifluridine (Lonsurf)

      Tipiracil is a thymidine phosphorylase inhibitor that increases trifluridine exposure by inhibiting its metabolism. Trifluridine is a thymidine-based nucleoside analog that incorporates into DNA, interferes with DNA synthesis, and inhibits cell proliferation. It is indicated for metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma previously treated with at least 2 prior lines of chemotherapy that included a fluoropyrimidine, a platinum, either a taxane or irinotecan, and if appropriate, HER2/neu-targeted therapy.

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