Efficacy and Safety of Apatinib for Elderly Patients with Advanced or Metastatic Gastric Cancer After Failure of at Least First-Line Chemotherapy: A Multi-Center, Single-Arm, Phase II Study.

BACKGROUND: Apatinib improves progression-free survival and overall survival with an acceptable safety profile in Chinese patients with chemotherapy-refractory advanced or metastatic gastric cancer. However, the efficacy and safety of apatinib are unclear for elderly patients. This study was undertaken to prospectively investigate the efficacy and safety of apatinib for elderly patients with unresectable advanced or metastatic gastric cancer, who experienced progression to at least one lines of chemotherapy. METHODS: This open-label, single-arm, phase II study enrolled patients aged ≥60 years with advanced gastric cancer, who experienced progression to one or more lines of chemotherapy at five centers in China. Patients received apatinib in an oral dose of 500mg or 250mg daily according to the research physicians' decision. The primary end point was progression-free survival, and the secondary end points were objective response rate, disease control rate, overall survival, and safety. RESULTS: Forty-eight patients were enrolled between June 2017 and September 2019. The median age was 65.5 years (range 60-80 years). Twenty-seven patients (56.3%) started treatment with an initial dose of 500 mg and 21 patients (43.7%) with 250 mg. The median progression-free survival and overall survival were 3.00 months (95% confidence interval, 2.17-3.84) and 8.10 months (95% confidence interval, 4.35-11.85), respectively. The objective response rate and disease control rate assessed by the investigators were 16.7% and 72.9%, respectively. The common side effects were fatigue (58.3%), hypertension (47.9%), abdominal pain (33.3%), proteinuria (29.2%), leukopenia (22.9%), and neutropenia (20.8%). Hypertension (22.9%) was the major grade 3/4 toxicity. CONCLUSION: These data suggest that apatinib is effective and relatively tolerable for elderly patients with unresectable advanced or metastatic gastric cancer who have received at least first-line chemotherapy.

Prostate stem cell antigen rs2294008 polymorphism differentially contributes to Helicobacter pylori-negative gastric cancer among various populations in China.

Gastric cancer is a lethal disease with a high mortality rate. Studies have suggested that prostate stem cell antigen (PSCA) rs2294008 polymorphism is associated with gastric cancer (GC). In this case-control study, we investigated rs2294008 polymorphism in the Tibet, Hui and Han nationalities in the Qinghai area of China. Genomic DNA was extracted from the peripheral blood of 286, 315 and 350 healthy volunteers and from 219, 233 and 265 Helicobacter pylori-negative non-cardia GC patients from the Tibet, Hui and Han populations, respectively. The rs2294008 polymorphism was analyzed by denaturing high-performance liquid chromatography. rs2294008 CT and TT genotypes were associated with GC both in the Tibet and Han populations (adjusted OR=1.51, 1.47, 2.01, 1.85; 95% CI, 1.04-2.19, 1.05-2.06, 1.04-3.88, 1.03-3.34; P=0.030, 0.025, 0.039, 0.040, respectively). rs2294008 TT genotype was associated with GC in the Hui population (adjusted OR=2.14; 95% CI, 1.29-3.55; P=0.003). Furthermore, when stratified by histopathology, the rs2294008 CT and TT genotypes were associated with diffuse GC in the Tibet and Han nationalities (adjusted OR=1.93, 1.73, 2.69, 2.86; 95% CI, 1.09-3.44, 1.01-2.95, 1.06-6.84, 1.27-6.46; P=0.025, 0.045, 0.038, 0.011, respectively). However, the rs2294008 TT genotype was associated with both intestinal and diffuse types of GC (adjusted OR=2.10, 2.21; 95% CI, 1.17-3.75, 1.12-4.38; P=0.012, 0.023, respectively) and the rs2294008 CT genotype was only associated with intestinal-type GC in the Hui nationalitiy group (adjusted OR=1.60; 95% CI, 1.04-2.47; P=0.034). The results therefore showed that rs2294008 may differentially contribute to GC among different nationalities in one area and its role is independent from Helicobacter pylori-infection.

Associations between interleukin-1 polymorphisms and gastric cancers among three ethnicities.

AIM: To investigate the associations between interleukin (IL)-1B and IL-1RN polymorphisms and gastric cancers among the Tibet, Hui and Han ethnicities. METHODS: Genomic DNA was extracted from peripheral blood of 210, 205, and 202 healthy volunteers and from 155, 158, and 197 gastric cancer patients from the Tibet, Hui, and Han populations, respectively. Polymorphisms in IL-1B and IL-1RN were analyzed by denaturing high-performance liquid chromatography. RESULTS: Carriers of the IL-1B-31 CC genotype had an increased risk of intestinal type gastric cancer [odds ratio (OR) = 2.17, P = 0.037] in the Tibet ethnicity. Carriers of the IL-1B 2/L genotype had an increased risk of both intestinal and diffuse types of gastric cancer (OR = 2.08, 2.31, P = 0.007, 0.016, respectively) in the Hui ethnicity. In the Han population, carriers of the IL-1B-31 CC, IL-1B-511CT, TT genotypes had increased risk of intestinal type gastric cancer (OR = 2.51, 2.74, 5.66, P = 0.005, 0.002, 0.000, respectively). CONCLUSION: IL-1B and IL-RN genotypes may differentially contribute to gastric cancer among the Tibet, Hui, and Han ethnicities in the Qinghai area of China.