What are treatment options for advanced unresectable gastric cancer?

Updated: May 21, 2019
  • Author: Elwyn C Cabebe, MD; Chief Editor: N Joseph Espat, MD, MS, FACS  more...
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Answer

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.

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%.

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. [47] (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. [48]  However, studies of S-1 have largely been limited to Japan, China, and Korea.

For metastatic gastric cancer, the NCCN recommends palliative chemotherapy or entry into a clinical trial. In April 2014, the FDA approved the angiogenesis inhibitor ramucirumab (Cyramza) for the treatment of advanced stomach cancer or gastroesophageal junction adenocarcinoma in patients with unresectable or metastatic disease following therapy with a fluoropyrimidine- or platinum-containing regimen. [49] This agent has also been designated as an orphan product.

Approval was based on two clinical trials. A study of 355 patients showed that those treated with ramucirumab (two thirds of patients) had better median overall survival (5.2 vs 3.8 mo) and better progression-free survival compared with patients who received placebo. A second study that compared the efficacy of ramucirumab plus paclitaxel with that of paclitaxel alone also showed improved overall survival in the group that received ramucirumab. The most common adverse events associated with ramucirumab included diarrhea and hypertension. [49]


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