What are treatment options for advanced unresectable gastric cancer?

Updated: Feb 23, 2021
  • Author: Elwyn C Cabebe, MD; Chief Editor: N Joseph Espat, MD, MS, FACS  more...
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Many patients present with distant metastases, carcinomatosis, unresectable hepatic metastases, pulmonary metastases, or direct infiltration into organs that cannot be resected completely.

In the palliative setting, radiotherapy provides relief from bleeding, obstruction, and pain in 50-75% of patients. The median duration of palliation is 4-18 months.

Surgical procedures such as wide local excision, partial gastrectomy, total gastrectomy, simple laparotomy, gastrointestinal anastomosis, and bypass also are performed with palliative intent, with a goal of allowing oral intake of food and alleviating pain.

Chemotherapy and biologic therapy

Platinum-based chemotherapy, in combinations such as epirubicin/cisplatin/5-FU or docetaxel/cisplatin/5-FU, represents the current first-line regimen. Other active regimens include irinotecan and cisplatin and other combinations with oxaliplatin and irinotecan. Results of cisplatin-based chemotherapy have been largely discouraging, with median time to progression of 3-4 months and overall survival of approximately 6-9 months despite reported response rates of up to 45%. For metastatic gastric cancer, the NCCN recommends palliative chemotherapy or entry into a clinical trial. [4]

Early results reported in 2007 by Japanese clinicians suggest some improvement in both response rates and survival with the oral fluoropyrimidine S-1 used alone or in combination with cisplatin. [51] (S-1 combines three investigational drugs: tegafur, a prodrug of 5-FU; gimeracil, an inhibitor of fluorouracil degradation; and oteracil or potassium oxanate, a GI tract adverse-effect modulator.) A 2017 systematic review and meta-analysis found evidence of a modest survival benefit with S-1 compared with 5-FU-containing regimens. [52]  However, studies of S-1 have largely been limited to Japan, China, and Korea.

Novel treatment strategies may be guided by the use of gene signatures. [53]  Kim et al reported that combined overexpression of MYCEGFR, and FGFR2 predicts a poor response of metastatic gastric cancer to treatment with cisplatin and 5-FU. [54]

Ishido et al reported that in patients receiving S-1 chemotherapy after gastrectomy for advanced gastric cancer, intratumoral mRNA expression of thymidylate synthase (TS) is an independent prognostic factor for response to chemotherapy. In 39 patients who received postoperative S-1, recurrence-free survival and overall survival were significantly longer in patients with low TS expression than in those with high TS expression (P=0.021 and 0.016, respectively), whereas in 40 patients treated with surgery only, TS expression did not correlate with survival. [55]

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