Efficacy of adjuvant chemotherapy in the treatment of gastric cancer

Written by doctors of Internal Oncology - Radiation Oncology Center, Vinmec Times City International Hospital

The effectiveness of adjuvant chemotherapy after radical gastrectomy in patients with gastric cancer is increasingly clear, although there is no consensus on the best approach, but in many places around the world. In the world, adjuvant chemotherapy is the preferred treatment strategy.

Stomach cancer is one of the most common cancers in the world. In Vietnam, according to Globocan 2016, stomach cancer ranks 3rd in both sexes after lung cancer and liver cancer with an age-standardized incidence rate of 23.7/100,000 population. In the world, the incidence of stomach cancer has decreased since the 1930s, but it is still the main cause of cancer death in the United States. The high mortality rate is related to the advanced stage of the disease at the time of diagnosis. In the West, the 5-year survival rate for surgically resected stage I gastric cancer is about 70 to 75%, while it drops to less than 35% in the stage I group. II and up. Studies have shown that adjuvant (postoperative) and neoadjuvant (preoperative) treatment have shown improved outcomes.
Efficacy of adjuvant chemotherapy after radical gastrectomy in gastric cancer patients is increasingly clear, although there is no consensus on a best approach, but in many places Worldwide, adjuvant chemotherapy is the preferred treatment strategy. On the other hand, a large trial in the US (INT0116) showed a significant benefit of adjuvant chemoradiotherapy.
This article will provide you with the results of some studies on adjuvant regimens, chemotherapy or radiotherapy for early gastric cancer after radical surgery.

The role of adjuvant radiation therapy stems from the observation that over 80% of patients die from recurrent gastric cancer. Although there are data showing the benefit of postoperative and intraoperative radiotherapy in patients with operable gastric cancer, 3 randomized trials incorporating postoperative chemotherapy and radiotherapy have shown a survival benefit. significantly compared with surgery alone.
2.1. Study INT 0116 The largest trial in the US with code number INT 0116 gave the most convincing data for chemoradiotherapy after radical surgery, especially since modern radiotherapy techniques are used and concurrently with 5FU to help increase radiation sensitivity.
The study was performed on 556 patients after radical gastrectomy (T1-4, N0-1), patients were randomly assigned to 2 groups, one for observation alone, one for adjuvant therapy. combination chemotherapy and radiotherapy. The majority of patients had T3, T4 tumors (68 and 69%) and 85% had lymph node metastases. 3-year disease-free survival (48% >< 31%) and 3-year survival (50% >< 41%) and median survival were significantly longer (36 >< 27 months). This benefit was maintained with longer follow-up (5-year survival 43% >< 28%).
In the chemoradiotherapy group, grade 3 and 4 toxicity occurred in 41% and 32% of patients, while 3 patients (accounting for 1%) died from treatment-related toxicity. The most common grade 3 or higher adverse events were hematologic (54%), gastrointestinal (33%), infectious (6%), neurological (4%). In study INT0116, chemoradiotherapy was administered with intravenous 5FU bolus or continuous infusion. Therefore, daily oral capecitabine is also often chosen because of its convenience for patients.
Patient selection
The selection of adjuvant patients after radical surgery for gastric cancer is not clear. There is particular controversy in the group of patients with stage IB (T2N0). The authors suggested that patients with gastric adenocarcinoma stage IB-IIA and have ≥2 risk factors (>60 years, size tumor size >5 cm, tumor in high position, high histology) prognosis will have 5-year survival rate of < 76% and this group is also recommended to receive adjuvant chemotherapy and radiotherapy.

Adjuvant chemotherapy:
A meta-analysis of 34 trials comparing adjuvant chemotherapy with surgery alone conducted in both Asia and the West, mortality risk in patients receiving adjuvant chemotherapy 15% off.
The regimens include epirubicin, cisplatin and FU (ECF); capecitabine in combination with oxalipatin (Xelox regimen) or TS-1
TS-1 is an oral 5FU drug, in the pill includes 3 different ingredients: florafur (tegafur), gimeracil (5-chloro-2,4 dihydropyridine , a potent inhibitor of DPD (dihydropyrimidine dehydrogenase) and oteracil (inhibits phosphorylation of FU in the intestine).
The benefit of TS-1 treatment was demonstrated in the Japanese ACTS-GC trial, of which 1059 Patients with stage II or III gastric cancer who had undergone D2 lymph node dissection were randomly assigned to 2 groups, 1 TS-1 treatment group (80 to 120 mg/day for 4 weeks, 6-week cycle, treatment for 1 year) and 1 group for follow-up only.5-year overall survival was significantly increased in the TS-1 treatment group (72% vs. 61%). 5 years in the INT0116 and MAGIC trials were only 43% vs 28% and 36% vs 28%
These results suggest that TS-1 treatment one year after surgery is the standard adjuvant therapy for the disease. gastric cancer in East Asia. It is difficult to know whether adjuvant TS-1 treatment (as demonstrated in the ACTS-GC trial) can be inferred to populations other than Japanese. In addition to Japan, European countries also approved the treatment for advanced stomach cancer. Currently, this drug is also licensed for circulation in Vietnam.
2.2. CLASSIC Trial The CLASSIC multicenter trial was conducted in Korea, China and Taiwan. A total of 1035 patients with stage II, IIIA, IIIB gastric cancer were randomly assigned to 2 groups: one group received postoperative 8 cycles of capecitabine (1000mg/m2 x 2 times/day from day 1 to day) 14, 21-day cycle) in combination with oxaliplatin (130mg/m2 day 1) and the other group had only D2 lymphadenectomy alone. 67% of patients completed 8 cycles of chemotherapy as planned and side effects (most commonly leukopenia, nausea, vomiting, thrombocytopenia and anorexia) changed the course of treatment. in 90% of patients. Despite this, at a median follow-up of 34 months, the chemotherapy group significantly improved 3-year disease-free survival (74% vs 59%), and overall survival (83% vs. with 69%. Currently, the results of the study and the Xelox regimen are also applied by many centers, including Vietnam.
Summary
For patients diagnosed at an early stage, after radical gastrectomy, chemotherapy or adjuvant chemotherapy should be given. Depending on the condition of the disease, general health, accompanying diseases... the doctor will choose the most suitable option, which may be chemotherapy alone or concurrent chemoradiotherapy.
Currently at Vinmec International General Hospital, both options are possible. In addition, patients can also combine with autologous immunotherapy and thermotherapy to improve treatment results.