Should be considered in patients with stage IV disease that can improve survival compared with best supportive care alone

• Co-morbidities, organ function & performance status must always be taken into consideration

Chemotherapy

• Combination regimens based upon a platinum-fluoropyrimidine doublet are generally used
  • Eg fluoropyrimidine (Fluorouracil [5-FU] or Capecitabine) & Cisplatin or Oxaliplatin
• Taxane-based regimens (eg Paclitaxel, Docetaxel) or Irinotecan plus Fluorouracil (5-FU) or platinum-based agents (Carboplatin, Cisplatin, Oxaliplatin) are alternative first-line chemotherapy option
  • Other preferred first-line therapies include Epirubicin, Cisplatin & Fluorouracil (ECF), Epirubicin, Cisplatin or Oxaliplatin, & Fluorouracil (5-FU) or Capecitabine (ECF modifications), Fluorouracil (ECF) Fluoropyrimidine (5-FU or Capecitabine) & Cisplatin or Oxaliplatin

• In patients of adequate performance status, second-line chemotherapy is associated with proven improvements in overall survival & quality of life compared with best supportive care
  • Preferred treatment options include Irinotecan, Docetaxel, Paclitaxel, Ramucirumab, or Ramucirumab & Paclitaxel
  • Other regimens include: Irinotecan & Cisplatin, Fluoropyrimidine (5-FU or Capecitabine) & Irinotecan, Docetaxel & Irinotecan

• Docetaxel, Cisplatin & 5-fluorouracil (DCF) regimen has been recommended for the treatment of patients with advanced gastric cancer, including esophagogastric-junction cancers, in patients who have not received prior chemotherapy
  • However, it was associated with increased myelosuppression & infectious complications

Interventional Radiotherapy

• Angiographic embolization may be considered in patients with acute bleeding not relieved by endoscopy

Radiotherapy

• Hypofractionated radiotherapy is an effective & well-tolerated treatment modality which may palliate bleeding, obstructive symptoms or pain in patients with symptomatic locally advanced or recurrent disease
• External beam radiotherapy may be considered for patients with malignant obstruction causing pain, & gastrointestinal bleeding

Surgery

• Although resection of the primary tumor is not generally recommended in the palliative setting, a small number of advanced disease patients may be deemed to be operable following a good response in systemic therapy
• Gastric resections should be reserved for palliation of symptoms in patients with incurable disease
  • Lymph node dissection is not required

Targeted therapies

• Human epidermal growth factor receptor-2 (HER-2) testing is recommended for all patients with inoperable, locally advanced, recurrent & metastatic disease at the time of diagnosis
• In human epidermal growth factor receptor-2 (HER-2)-positive gastric cancer, addition of Trastuzumab to a Cisplatin-Fluoropyrimidine doublet showed clinically & statistically significant improvements in response rate, progression-free survival & overall survival
• Trastuzumab in combination with Ciplatin & Fluoropyrimidine (first-line) or with other chemotherapy agents (eg Capecitabine or 5-fluorouracil & Cisplatin) is the standard care regimen
• Trastuzumab was limited only in patients with an immunohistochemistry score of 3+ or 2+ &  fluorescence in situ hybridization (FISH)-positive
• Targeting vascular endothelial growth factor receptors (VEGFR) with the anti-vascular endothelial growth factor receptors 2 (VEGFR-2) monoclonal antibody Ramucirumab showed promising results in patients with advanced gastric or EGJ adenocarcinoma positive for disease progression despite treatment with platinum-/fluoropyrimidine-based doublet/triplet chemotherapy
• Ramucirumab may be given alone or in combination with Paclitaxel