Modern Oncological Approaches to Gastric Adenocarcinoma

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Key points

  • Gastric cancer (GC) is the fourth most common cancer in men and the fifth most common cancer in women worldwide.

  • Surgery is the key for curing patients with localized GC. However, surgery alone is insufficient to achieve the highest possible cure rate, which can be obtained by the addition of adjunctive therapies.

  • Advanced GC is an incurable condition; however, it is now possible to prolong survival with oncologic therapies.

  • Patients with advanced GC with Her2-neu protein overexpression can

Localized gastric cancer (LGC)

Baseline clinical stage should be established meticulously.3 Although baseline clinical stage is not as highly associated with long-term outcome as the surgical pathology stage,4 the baseline clinical stage does help to define the short-term therapeutic strategy. It is important to emphasize that physician(s) from one discipline (eg, a gastroenterologist or a surgeon) should not decide the initial therapeutic strategy of LGC but that a consensus decision, derived from a multidisciplinary

Postoperative Adjuvant Chemoradiation

The most important study that established this strategy firmly in the West is the Intergroup 0116 trial, headed by the Southwest Oncology Group.7 This trial was based on prior nonrandomized observations in patients with LGC who received chemoradiation therapy. This trial was a phase 3 study that compared observation after surgery (control) with chemoradiation adjuvant after following surgery (experimental arm).7

Key points about the INT0116 trial

  • Recruitment duration: 1991–1998

  • Total number of

Advanced GC (AGC)

There are only a few agents that are associated with level 1 evidence for an overall survival advantage in AGC. These are docetaxel,20 cisplatin,21 and trastuzumab.22

It is also clear that giving 2 cytotoxic agents together is better than giving one alone.21 Whether there is an additional advantage from combining 3 cytotoxic agents is often debated, but it is likely minor. From a drug development perspective, most regulatory agencies currently accept a 2-cytotoxic-agent combination of a platinum

Important genes and pathways in GC

Alterations in the following pathways seem important in the pathobiology of GC: ERBB2 (Her-2), angiogenesis, phosphatidyl inositol-3-kinase (PI3K)-AKT-mammalian target of rapamycin (mTOR), c-MET, and fibroblast growth factor receptor 2 (FGFR2). However, further research is expected to uncover more targets.

Summary

When evaluating newly diagnosed patients with GC, one must first establish whether a patient has AGC or LGC. Patients with LGC must undergo multidisciplinary evaluation and discussion before starting therapy. Surgery alone is inadequate in most patients with LGC, and adjunctive therapies should be considered. Surgery should be performed by an experienced high-volume surgeon, and at least 15 nodes must be evaluated.

For patients with AGC, much more research focusing on the molecular biology of GC

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References (37)

  • J.S. Macdonald et al.

    Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction

    N Engl J Med

    (2001)
  • S.R. Smalley et al.

    Updated analysis of SWOG-directed intergroup study 0116: a phase III trial of adjuvant radiochemotherapy versus observation after curative gastric cancer resection

    J Clin Oncol

    (2012)
  • C.S. Fuchs et al.

    Postoperative adjuvant chemoradiation for gastric or gastroesophageal junction adenocarcinoma using epirubicin, cisplatin, infusional fluourouracil before and after infusional fluorouracil and radiotherapy compared with bolus fluorouracil/leucovorin before and after chemoradiation. Intergroup trial CALGC 80101

    J Clin Oncol

    (2011)
  • J. Lee et al.

    Phase III trial comparing capecitabine plus cisplatin versus capecitabine plus cisplatin with concurrent capecitabine radiotherapy in completely resected gastric cancer with D2 lymph node dissection: the ARTIST rial

    J Clin Oncol

    (2012)
  • J.C. Yao et al.

    Gastric cancer

    Curr Opin Gastroenterol

    (2000)
  • S. Sakuramoto et al.

    Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine

    N Engl J Med

    (2007)
  • M. Sasako et al.

    Five-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 versus surgery alone in stage II or III gastric cancer

    J Clin Oncol

    (2011)
  • Y.J. Bang et al.

    Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial

    Lancet

    (2012)
  • Cited by (0)

    This work was supported in part by The Park Family, Caporella Family, Bikoff Family, Cantu Family, Fairman Family, Dallas Family, Oaks Family, Sultan Family, Dio Family, Frazier Family, the Kevin Fund, the Schecter Private Foundation, and the Rivercreek Foundation.

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