From the Guidelines
For unresectable gastric cancer, the recommended first-line chemotherapy regimens include a fluoropyrimidine combined with a platinum agent, such as the FOLFOX regimen or the XELOX/CAPOX regimen, with the addition of trastuzumab for HER2-positive tumors, as stated in the 2022 NCCN clinical practice guidelines in oncology 1. The treatment of unresectable gastric cancer involves a multidisciplinary approach, with systemic therapy playing a crucial role in providing palliation, improved survival, and enhanced quality of life.
- The FOLFOX regimen consists of oxaliplatin at 85 mg/m² on day 1, leucovorin 400 mg/m² on day 1, and 5-FU as a 400 mg/m² bolus followed by 2400 mg/m² over 46 hours, repeated every 2 weeks.
- The XELOX/CAPOX regimen includes capecitabine 1000 mg/m² twice daily for 14 days and oxaliplatin 130 mg/m² on day 1, repeated every 3 weeks.
- For patients with HER2-positive tumors, trastuzumab is added to chemotherapy, as recommended by the NCCN guidelines 1. The selection of chemotherapy regimens depends on patient performance status, comorbidities, and prior therapy response, with dose adjustments needed for renal or hepatic impairment.
- Second-line treatment options include paclitaxel with ramucirumab, irinotecan, or docetaxel, which have shown efficacy in clinical trials 1. The implementation of biomarker testing, including HER2 status, microsatellite instability (MSI) status, and the expression of programmed death-ligand 1 (PD-L1), has had a significant impact on clinical practice and patient care, as stated in the 2022 NCCN guidelines 1.
From the FDA Drug Label
GC: 75 mg/m2 followed by cisplatin 75 mg/m2 (both on day 1 only) followed by fluorouracil 750 mg/m2 per day as a 24-hr IV (days 1-5), starting at end of cisplatin infusion (2.4) The chemotherapy regimen for unresectable gastric cancer is:
- Docetaxel: 75 mg/m2
- Cisplatin: 75 mg/m2
- Fluorouracil: 750 mg/m2 per day as a 24-hr IV (days 1-5) 2
From the Research
Chemotherapy Regimens for Unresectable Gastric Cancer
The following chemotherapy regimens are used for unresectable gastric cancer:
- Biweekly docetaxel, fluorouracil, leucovorin, oxaliplatin (TEF) regimen, which has shown an objective response rate of 66% and median progression-free survival of 6.3 months 3
- Modified FOLFOX-4 (mFOLFOX-4) regimen, which has shown an overall response rate of 41.1% and median overall survival of 11.9 months in elderly patients and 11.2 months in nonelderly patients 4
- Docetaxel, oxaliplatin, and 5-fluorouracilo (DOF) regimen, which has shown an overall response rate of 73.2% and median overall survival of 10.3 months 5
- Regimens including oral 5-FU agents such as S1/Xeloda and platinum preparations, as well as Trastuzumab for HER2-positive cases 6
First-Line Chemotherapy
First-line chemotherapy for unresectable gastric cancer typically consists of multidrug regimens, including:
- Oral 5-FU agents such as S1/Xeloda
- Platinum preparations
- Trastuzumab for HER2-positive cases 6
Second- and Third-Line Chemotherapy
Second- and third-line chemotherapy regimens include:
- Taxanes
- Ramucirumab (R-mab)
- Nivolumab (N-mab) 6