I. Overview
Survival in gastric cancer has been reported to be higher in Asian countries than in the U.S. Initially, this survival difference was thought to be due to differences in surgical technique, pathologic staging and/or tumor biology. 2008ASCO (abstr 4540) Artinyan et al. found that overall survival was significantly better in Asian Americans than in white Americans among patients with stage I-III resectable gastric adenocarcinoma in the U.S. population, and this result was related to disease stage This outcome was not related to disease stage and the number of lymph node metastases or surgical technique, and the difference in survival between East and West seems to be influenced by other factors such as tumor biology (1). Not coincidentally, Husain et al. (2008abstr 15511) studied polymorphisms of prothrombin receptor 1 (PAR1), endothelial inhibitory hormone (ES), and interleukin-8 (IL-8) in Asians, Caucasians, and Hispanics to investigate whether the frequency of these genetic polymorphisms contributed to the variability in time to tumor recurrence (TTR) in postoperative gastric cancer patients by race. CONCLUSION: Allele frequencies were statistically different between races only for PAR1 and ES, with a median TTR of 7.0 years for Asians, 3.7 years for Hispanics, and 1.7 years for Caucasians. Gastroesophageal junction tumors (GEJC) had shorter TTR compared to tumors in other locations (2.1 years vs. 3.1 years, p= 0.021) (2). Ma Ning, Department of Medical Oncology, Henan Provincial People’s Hospital
II. Relationship between ethnic variability and differences in 1st and 2nd line chemotherapy drug selection
It is possible that the geographical variability in the site of disease onset and the racial variability of the Eastern and Western populations contribute to the variability in the propensity to choose 1st and 2nd line treatment. Despite the extensive efforts of scholars in the East and West for the treatment of advanced gastric cancer, the globally accepted standard regimen has not been determined so far, and the 2009 NCCN 2- and 3-linked regimens based on fluorouracil + cisplatin +/- anthracyclines or doxorubicin remain the most widely accepted 1st-line standard regimens worldwide (ECF, DCF regimens – -NCCN Evidence Level 1), where FU can be replaced by S – 1 or capecitabine and cisplatin by oxaliplatin. Irinotecan (V306) based 1st line regimen (combined with cisplatin or fluorouracil-based) has a level of evidence grade 2, but because its combination with fluorouracil-based (FU or XELODA) avoids the severe gastrointestinal response of cisplatin, it becomes the best 1st line option for patients who cannot tolerate the gastrointestinal response to cisplatin.JCOG9912, SPIRITS trial makes S-1+DDP the the most reasonable 1st-line treatment option in Japan and a strong challenge to capecitabine, but there is still a lack of robust phase III trial data for S-1 in Western countries (3-7). Although the worldwide FLAGS trial concluded no statistical difference in overall survival and only quality of life improvement in CS (DDP+S-1) was superior to CF (DDP+FU), the cisplatin dose in the CS regimen was 75% of that in the control CF regimen and the S-1 dose was at least 37.5% lower than that in the SPIRITS Japan study (8).
Throughout the world, the internationalization of oncology trials is progressing at an increasing pace, with more than half of Japanese and Korean patients enrolled in trials, and East Asian countries are playing an increasingly important role in this field (9). As early as 2006 Park, Korea conducted a European Organization for Research and Treatment of Cancer (EORTC) QLQ- C30 and Hospital Anxiety Depression Scale (HADS) study in patients with advanced gastric cancer undergoing 2 lines of treatment, showing that 2 lines of chemotherapy improved baseline quality of life and HADS scores (10). 2007 A study from Japan showed that 1 line CPT-11+S-1 patients (n=33) with metastatic or progressive gastric cancer who failed treatment received 2 lines of chemotherapy and compared the OS of best supportive care was 444 days vs 230 days (p = 0.013) ,with no difference in overall survival with or without 2 lines containing S-1 (11). 2008 Catalano from the Italian Department of Medical Oncology proposed 5 risk factors, PS=2, HB ≤11.5 g/l, serum CEA >50 ng/ ml, metastases ≥3, and TTP ≤6mos, containing 0, 1-2, and 3-5 risk factors OS of 12.7, 7.1, and 3.3 months, respectively, with patients with fewer risk factors benefiting more from 2nd-line chemotherapy (12). Although there is still much controversy about the standard regimen for 1st-line therapy, let us set aside the controversy for a moment and perform a retrospective analysis of patients who failed 1st-line therapy. 2009 Lee in Korea analyzed 1455 patients treated and concluded that PS status, baseline HBG levels determined which patients were more likely to benefit from 2nd-line chemotherapy. This also suggests to us that the physical status of the patient rather than age is the key factor in deciding whether to treat in 2nd line or not (13).
III. Common drug therapy options for advanced relapsed gastric cancer
IV. Ethnic variability leads to a preference for drug selection for first- and second-line gastric cancer treatment, but whatever order is chosen does not seem to make much difference in overall efficacy and survival in gastric cancer, and although two triple regimens have demonstrated a survival prolongation advantage in Western studies, the gold standard for advanced gastric cancer treatment is still vainly awaited. The improvement of third-generation chemotherapeutic drugs, bound paclitaxel in non-gastric cancers offers the possibility of high dose high efficiency and low toxicity in the treatment of advanced gastric cancer; the earlier proposed double platinum regimen combined with teniposide (with or without fluorouracil) is highly efficient and low toxicity, with both basic and clinical validation, and is a model worthy of further exploration; the improvement of drug construction (albumin-bound paclitaxel) offers the possibility of cytotoxic chemotherapy In Japan, S-1+DDP is the standard regimen for 1st-line treatment, and CPT-11 and paclitaxel have become the superior choice for 2nd-line gastric cancer treatment; the combination with biological agents such as P53 adenovirus, tumor necrosis factor, Endo (vascular endothelial inhibitor) and thalidomide is expected to overcome the first-line resistance of patients and re-increase the drug sensitivity; some small molecule targeted drugs (trastuzumab, bevacizumab and lapatinib) are in large international clinical trials; tyrosine kinase inhibitors of rapamycin and C-Met, which are also in early clinical studies with biological performance evaluation, show high responsiveness in combination with cytotoxic chemotherapeutic drugs; according to different biological status and Due to the high incidence of gastric cancer in Asia and the widespread use of endoscopy, it is easier to obtain tumor pathology tissue for research, so many large clinical and basic trials conducted may greatly benefit the treatment of advanced gastric cancer, especially the frontiers of targeted and biological 1st and 2nd line therapy! The joint efforts of scholars from the East and the West will not only advance the clinical treatment of advanced relapsed refractory gastric cancer, but also promote the rapid advancement of biopharmaceuticals. The joint development of clinical medicine and biomedicine brings new hope to break the bottleneck of gastric cancer treatment!