Chemotherapy for gastric cancer is divided into preoperative neoadjuvant chemotherapy, postoperative adjuvant chemotherapy, and palliative chemotherapy. The neoadjuvant and adjuvant chemotherapy regimens are relatively consistent, and those with effective neoadjuvant chemotherapy can continue to use the original regimen for adjuvant chemotherapy after surgery. The palliative chemotherapy for gastric cancer can be expressed as “chemotherapy for recurrent or metastatic gastric cancer”, and the specific plan is somewhat different from the above.
Different chemotherapy regimens
Neoadjuvant and adjuvant chemotherapy
For preoperative neoadjuvant chemotherapy for gastric cancer, the National Comprehensive Cancer Network (NCCN) guidelines for gastric cancer and the Chinese guidelines for gastric cancer recommend the following regimens:
- Oxaliplatin in combination with capecitabine, the XELOX regimen
- Docetaxel in combination with oxaliplatin and fluorouracil, i.e., the FLOT regimen
- Fluorouracil in combination with cisplatin (Cisplatin), the FP regimen
- Oxaliplatin in combination with fluorouracil, the FLOFOX regimen
- Oxaliplatin in combination with S-1 (SOX)
- Epirubicin in combination with cisplatin and fluorouracil (ECF) and its modifications
For patients in complete pathological remission confirmed by surgical resection of the specimen after neoadjuvant therapy, there are no studies to confirm the impact of postoperative changes to the original chemotherapy regimen or no postoperative adjuvant therapy on disease outcome, therefore, the Chinese gastric cancer guidelines still recommend postoperative adjuvant chemotherapy according to the original chemotherapy regimen.
For postoperative chemotherapy for gastric cancer, the NCCN gastric cancer guidelines and the Chinese gastric cancer guidelines recommend oxaliplatin in combination with capecitabine (XELOX) or S-1 monotherapy. The following regimens are also available as postoperative adjuvant chemotherapy options for gastric cancer:
- Oxaliplatin in combination with fluorouracil regimen (FLOFOX)
- Oxaliplatin in combination with the S-1 regimen (SOX)
- Capecitabine in combination with cisplatin (XP)
Palliative chemotherapy
For patients with gastric cancer who are unable to undergo radical gastric cancer surgery or have recurrent metastases after radical surgery, the main treatment goals are to relieve clinical symptoms, improve quality of life, and prolong survival.
Fluorouracil, platinum and paclitaxel are the main chemotherapy drugs for advanced gastric cancer. Most advanced gastric cancers are treated with combination regimens, and although the literature reports that combination chemotherapy regimens are more effective than single-agent chemotherapy, single-agent chemotherapy can still be considered for patients who cannot tolerate combination chemotherapy.
Priority of different chemotherapy regimens
First-line chemotherapy
HER2 (i.e., human epidermal growth factor receptor 2)-positive gastric cancer
The NCCN Guidelines for Gastric Cancer and the Chinese Gastric Cancer Guidelines recommend trastuzumab in combination with fluorouracil / capecitabine + cisplatin, taking into account the patient’s physical condition, age, and underlying disease, or trastuzumab in combination with the following chemotherapy regimens:
- Oxaliplatin + capecitabine
- S-1 + cisplatin
- docetaxel + oxaliplatin + capecitabine
- docetaxel + cisplatin + S-1
- Single agent (e.g., capecitabine)
HER2-negative gastric cancer
The NCCN Guidelines for Gastric Cancer and the Chinese Gastric Cancer Guidelines recommend the following two-drug combination regimen, taking into account the patient’s physical condition, age, and underlying disease:
- Platinum-based chemotherapy
- Platinum-based chemotherapy, i.e., cisplatin + fluorouracil-based (5-fluorouracil / capecitabine / S-1)
- Oxaliplatin as the base chemotherapy, i.e. oxaliplatin + fluorouracil-based (5- fluorouracil / capecitabine /S-1)
- Paclitaxel as the base chemotherapy, i.e. paclitaxel / docetaxel + 5- fluorouracil / capecitabine / S-1
The following three-drug combination regimen is indicated for patients with good physical status and a large tumor load:
- Epirubicin in combination with cisplatin and fluorouracil regimen (ECF)
- Paclitaxel/docetaxel combined with cisplatin and fluorouracil regimen (DCF)
Patients with gastric cancer in average physical condition or in combination with other underlying diseases may opt for single-agent chemotherapy after full consideration of the pros and cons, for example:
- Iritecan (Irinotecan)
- Fluorouracil
- Paclitaxel
Second-line and beyond chemotherapy
Patients with gastric cancer who have failed first-line chemotherapy are treated with chemotherapy regimens based on single agents, such as docetaxel, irinotecan, and paclitaxel, but the choice of second-line and beyond chemotherapy agents for gastric cancer is limited, the efficacy is poor, and there is heterogeneity in gastric cancer, such as race and site, so patients may be able to participate in clinical trials with newer agents that may have better efficacy, as long as conditions allow.
In conclusion, the choice of chemotherapy regimens for gastric cancer is complex and varied, and the exact choice of regimen requires individualized decision making by the physician based on the patient’s tumor stage, physical condition, and other specific circumstances. (Contributed by Xiaoyu Guo, Department of Gastrointestinal Oncology, The First Hospital of China Medical University)