Palliative chemotherapy with or without immunotherapy

Of all the combination regimens, epirubicin, cisplatin, and 5-FU (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 5-FU, doxorubicin, and methotrexate (FAMTX).[18]

Of all the combination regimens, epirubicin, cisplatin, and 5-FU (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 5-FU, doxorubicin, and methotrexate (FAMTX).[18]

The group who received ECF had a significantly longer median survival (8.9 vs. 5.7 months, P = .0009) than the FAMTX group.[18][Level of evidence A1]

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).[4][Level of evidence A1]

Oxaliplatin or capecitabine are often substituted for cisplatin and 5-FU within the ECF regimen on the basis of results from the REAL-2 trial (ISRCTN51678883).[10] This randomized trial of 1,002 patients with advanced esophageal, gastroesophageal junction, or gastric cancer utilized a 2 × 2 design.

Oxaliplatin or capecitabine are often substituted for cisplatin and 5-FU within the ECF regimen on the basis of results from the REAL-2 trial (ISRCTN51678883).[10] This randomized trial of 1,002 patients with advanced esophageal, gastroesophageal junction, or gastric cancer utilized a 2 × 2 design.

The trial demonstrated 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 cisplatin and 5-FU.[19] Time-to-treatment progression (TTP) was the primary end point.

An international collaboration of investigators randomly assigned 445 patients with metastatic gastric cancer to receive docetaxel, cisplatin, and 5-FU (DCF) or cisplatin and 5-FU.[19] Time-to-treatment progression (TTP) was the primary end point.

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%).

An international collaboration of investigators randomly assigned 445 patients with metastatic gastric cancer to receive docetaxel, cisplatin, and 5-FU (DCF) or cisplatin and 5-FU.[19] Time-to-treatment progression (TTP) was the primary end point.

The median OS was significantly longer for patients who received DCF compared with patients who received cisplatin and 5-FU (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%).[19][Level of evidence A1]

An international collaboration of investigators randomly assigned 445 patients with metastatic gastric cancer to receive docetaxel, cisplatin, and 5-FU (DCF) or cisplatin and 5-FU.[19] Time-to-treatment progression (TTP) was the primary end point.

The toxicity rates were high in both arms.[20]

An international collaboration of investigators randomly assigned 445 patients with metastatic gastric cancer to receive docetaxel, cisplatin, and 5-FU (DCF) or cisplatin and 5-FU.[19] Time-to-treatment progression (TTP) was the primary end point.

Febrile neutropenia was more common in patients who received DCF (29% vs. 12%). The death rate was 10.4% in patients who received DCF and 9.4% in patients who received cisplatin and 5-FU.

It is unclear if cisplatin and 5-FU should be considered as an index regimen for the treatment of patients with metastatic gastric cancer.[20] The results of a study that randomly assigned 245 patients with metastatic gastric cancer to receive cisplatin and 5-FU, FAMTX, or etoposide, leucovorin, and 5-FU (ELF) demonstrated no significant difference in response rate, progression-free survival (PFS), or OS between the arms.[5]

It is unclear if cisplatin and 5-FU should be considered as an index regimen for the treatment of patients with metastatic gastric cancer.[20] The results of a study that randomly assigned 245 patients with metastatic gastric cancer to receive cisplatin and 5-FU, FAMTX, or etoposide, leucovorin, and 5-FU (ELF) demonstrated no significant difference in response rate, progression-free survival (PFS), or OS between the arms.[5]

Grades 3 and 4 neutropenia occurred in 35% to 43% of patients on all arms, but severe nausea and vomiting was more common in patients in the cisplatin-and-5-FU arm and occurred in 26% of those patients.[5][Level of evidence B3]