Standard treatment options:
- Palliative chemotherapy with:
- Fluorouracil (5-FU).[1,2,3]
- Epirubicin, cisplatin, and 5-FU (ECF).[4,5]
- Epirubicin, oxaliplatin, and capecitabine (EOX).
- Cisplatin and 5-FU (CF).[7,3]
- Docetaxel, cisplatin, and 5-FU.
- Etoposide, leucovorin, and 5-FU (ELF).
- 5-FU, doxorubicin, and methotrexate (FAMTX).
- Trastuzumab, cisplatin, and either 5-FU or capecitabine in patients with HER2-positive tumors (3+ on immunohistochemistry [IHC] or fluorescence in situ hybridization [FISH]-positive).
- Endoluminal laser therapy, endoluminal stent placement, or gastrojejunostomy, may be helpful to patients with gastric obstruction.
- Palliative radiation therapy may alleviate bleeding, pain, and obstruction.
- Palliative resection should be reserved for patients with continued bleeding or obstruction.
Standard chemotherapy versus best supportive care for patients with metastatic gastric cancer has been tested in several clinical trials, and there is general agreement that patients who receive chemotherapy live for several months longer on average than patients who receive supportive care.[11,12,13][Level of evidence: 1iiA] During the last 20 years, multiple randomized studies evaluating different treatment regimens (monotherapy vs. combination chemotherapy) have been performed in patients with metastatic gastric cancer with no clear consensus emerging as to the best management approach. A meta-analysis of these studies demonstrated an hazard ratio (HR) of 0.83 for overall survival (OS) (95% confidence interval [CI], 0.74–0.93) in favor of combination chemotherapy.
Of all the combination regimens, ECF is often considered the reference standard in the United States and Europe. In one European trial, 274 patients with metastatic esophagogastric cancer were randomly assigned to receive either ECF or FAMTX. The group who received ECF had a significantly longer median survival (8.9 vs. 5.7 months, P = .0009) than the FAMTX group.[Level of evidence: 1iiA] In a second trial that compared ECF with mitomycin, cisplatin, and 5-FU (MCF), there was no statistically significant difference in median survival (9.4 vs. 8.7 months, P = .315).[Level of evidence: 1iiA]
Oxaliplatin and capecitabine are often substituted for cisplatin and 5-FU within the ECF regimen as a result of data from the REAL-2 trial (ISRCTN51678883). This randomized trial of 1,002 patients with advanced esophageal, gastroesophageal junction, or gastric cancer utilized a 2 × 2 design to demonstrate noninferior median OS in patients treated with capecitabine rather than 5-FU (HRdeath = 0.86; 95% CI, 0.82–0.99) and in patients treated with oxaliplatin in place of cisplatin (HRdeath = 0.92; 95% CI, 0.80–1.10).
An international collaboration of investigators randomly assigned 445 patients with metastatic gastric cancer to receive docetaxel, cisplatin, and 5-FU (DCF) or CF. Time-to-treatment progression (TTP) was the primary endpoint. Patients who received DCF experienced a significantly longer TTP (5.6 months; 95% CI, 4.9–5.9; vs. 3.7 months; 95% CI, 3.4–4.5; HR, 1.47; 95% CI, 1.19–1.82; log-rank P < .001; risk reduction 32%). The median OS was significantly longer for patients who received DCF versus patients who received CF (9.2 months; 95% CI, 8.4–10.6; vs. 8.6 months; 95% CI, 7.2–9.5; HR, 1.29; 95% CI, 1.0–1.6; log-rank P = .02; risk reduction = 23%).[Level of evidence: 1iiA] There were high toxicity rates in both arms. Febrile neutropenia was more common in patients who received DCF (29% vs. 12%), and the death rate on the study was 10.4% for patients on the DCF arm and 9.4% for patients on the CF arm.