What is the treatment for stage 4 gastric cancer?

Treatment for Stage 4 Gastric Cancer

Patients with stage 4 gastric cancer should receive palliative combination chemotherapy with a platinum-fluoropyrimidine doublet or triplet regimen, as this improves survival by approximately 6.7 months compared to best supportive care alone. 1

Primary Treatment Approach

First-Line Palliative Chemotherapy

Combination chemotherapy is the standard of care for stage IV gastric cancer with adequate performance status. 1

Preferred Regimens (Platinum-Fluoropyrimidine Based)

The most established first-line options include:

• EOX (epirubicin, oxaliplatin, capecitabine) is the preferred triplet regimen, demonstrating median overall survival of 11.2 months versus 9.9 months with ECF (HR 0.80, P=0.02), with reduced thromboembolism rates (7.6% vs 15.1%) and no need for indwelling venous access 1

• ECF (epirubicin 50 mg/m², cisplatin 60 mg/m², continuous 5-FU 200 mg/m²/day) remains among the most active and well-tolerated regimens 1

• ECX (epirubicin, cisplatin, capecitabine) is an acceptable alternative with comparable efficacy to ECF 1, 2

• Platinum-fluoropyrimidine doublets (cisplatin or oxaliplatin combined with 5-FU or capecitabine) are generally used and appropriate for most patients 1

Triplet vs Doublet Considerations

Meta-analyses demonstrate that three-drug regimens including both an anthracycline and platinum with fluoropyrimidine provide survival benefit over two-drug combinations, but at the cost of increased toxicity. 1

• Triplet regimens should be reserved for fit patients with high tumor burden or potential for secondary resectability 1, 3
• Doublet regimens are preferred for the majority of patients based on balanced benefit-to-risk ratio 3

Alternative First-Line Options

• Docetaxel-containing regimens: DCF (docetaxel 75 mg/m², cisplatin 75 mg/m², 5-FU 750 mg/m²/day × 5 days every 3 weeks) increases activity but significantly increases toxicity including febrile neutropenia 1, 4

• Irinotecan plus 5-FU/leucovorin has similar activity to 5-FU/cisplatin and can be considered in selected patients 1

• Oxaliplatin-containing regimens may extend survival by less than one month compared to cisplatin-containing regimens (HR 0.81) with potentially better tolerability 1, 5

• Capecitabine can substitute for 5-FU with superior overall survival in meta-analysis within doublet and triplet regimens 1

HER2-Positive Disease

All patients with stage IV gastric cancer must be tested for HER2 status. 2, 6

• For HER2-positive tumors, add trastuzumab to cisplatin and fluoropyrimidine (5-FU or capecitabine), as this has demonstrated prolonged survival 3, 5

Second-Line Chemotherapy

Second-line chemotherapy is recommended for patients with adequate performance status after first-line failure, as it provides proven survival benefit. 1, 5

• Taxane-based regimens (docetaxel or paclitaxel) and irinotecan-containing regimens have shown responses in phase II trials 1
• Ramucirumab (anti-VEGFR2 antibody) alone or combined with paclitaxel is an established second-line option 3, 7
• For patients relapsing >3 months after first-line chemotherapy, consider re-challenging with the same regimen 1

Considerations for Patient Selection

Co-morbidities, organ function, and performance status must always be taken into consideration before initiating chemotherapy. 1

• Elderly and infirm patients should be considered for monotherapy and early dose modifications 3
• Patients with poor performance status may be better served with best supportive care alone 1

Role of Surgery in Stage IV Disease

Resection of the primary tumor is not generally recommended in the palliative setting. 1

• A small number of patients may be deemed operable following good response to systemic therapy (conversion surgery) 1, 7
• Response should be assessed with interval CT imaging of chest, abdomen, and pelvis 1

Critical Pitfalls to Avoid

• Do not use docetaxel 100 mg/m² monotherapy in previously treated patients, as this dose was associated with increased hematologic toxicity, infection, and treatment-related mortality 4

• Do not omit HER2 testing in metastatic disease, as this identifies patients who benefit from trastuzumab addition 2, 6

• Do not administer chemotherapy to patients with neutrophil counts <1500 cells/mm³ or significant hepatic dysfunction (bilirubin >ULN) 4

• Do not use intensive routine follow-up surveillance, as there is no evidence this improves outcomes; symptom-driven visits are recommended 1