| Background and Objectives: Currently, no standard chemotherapeutic regimen has been widely accepted for the treatment of advanced gastric cancer(ADC). During the past decade the researches on the chemotherapy treatment of advanced gastric cancer have focused on the improvement of the administration route of the existing combination chemotherapy regimens, the effect evaluation of the existing chemotherapy regimens and the application of new chemotherapy medicines. The randomized, multinational phase II/III trial(V325), as one of the most significant progresses in the first line treatment of advanced gastric cancer, selected docetaxel, cisplatin, and fluorouracil(DCF) over docetaxel and cisplatin in the phase II part for comparison against cisplatin and fluorouracil(CF; reference regimen) in the phase III part. The results revealed that the DCF group significantly improved median time to progression(TTP), median survival time and response rate, but resulted in some increase in toxicity, such as bone marrow suppression. Molecular targeted therapies or combination chemotherapy in advanced gastric cancer have become hot investigation, such as cetuximab, bevacizumab, trastuzumab, gefitinib, and erlotinib. Molecular targeted therapies have been proven to be with high efficacy and prolonged progression free survival by evidence-based medicine method in the treatment of ADC. Thalidomide, a potent agent in anti-angiogenesis, improving immunity and treating insomnia, has become one of the most popular targeted therapy medicines, especially its low cost.DOF as an improvement regimen of DCF had the same efficacy with DCF, but showed a significant improvement in bone marrow suppression and patient tolerance. This study aims to evaluate the efficacy and toxicity of DOF combination with thalidomide in the first-line treatment of advanced gastric cancer.Method: All of 76 enrolled patients were histologically confirmed un-resectable and untreated advanced gastric cancer with at least one measurable lesion. The enrolled patients were assigned to a control group(DOF group) or an experimental group(DOF combination with thalidomide group) in a 1:1ratio using the central randomization method. The control group’s dosage schedule was TXT 40mg/m2 on d1; L-OHP 85mg/m2 on d2; LV200mg/m2 on d2, 3, 5-FU 400mg/m2(intravenous infusion) on d2, 3; 5-FU 1200mg/m2 continuous intravenous infusion 44 h. All schedules were repeated every 14 d. The experiment group was given the same dosage schedule, combined with thalidomide 200mg(oral administration) per night. During treatment, patients were required to undergo neck, chest, abdomen and pelvis enhanced computed-tomography(CT) scans and carcinoembryonic antigen(CEA), CA72-4, CA199 test every 4 chemotherapy cycles. Treatment of chemotherapy related complications: According to the degree of bone marrow suppression, colony-stimulating factor(G-CSF), thrombopoietin(TPO)/ IL-11, and erythropoietin(EPO) were used to treat the reduction in white blood cells, platelets, and red blood cells, respectively. 5-HT3 antagonists were used in the treatment of gastrointestinal reactions such as nausea and vomiting. Mecobalamine and warm therapy were applied to reduce the symptoms of chemotherapy induced peripheral neurotoxicity. Statistical analysis was performed using SPSS® version 15.0. Numericaldata were analyzedusingχ2 test. The Kaplan-Meier method was used for survival analysis, and differences in survival were estimated using the log-rank test. A p-values <0.05 were considered significant.Results: The average chemotherapy cycle of the DOF combination with thalidomide group was 6 cycles(1 CR, 22 PR, 10 SD and 5 PD) and the RR was 60.5%. The average chemotherapy cycle of the DOF group was 5.8(2-10) cycles(1 CR, 17 PR, 10 SD and 10 PD) and the RR was 47.4%.Efficacywas higher with DOF combination with thalidomide group versus DOF group. The difference in short-term curative effect was statistically significant(P<0.05). The median time to progression(m TTP) between DOF combinationwith thalidomide group and DOF group were 6.9 months and 5.8 months(P<0.05);the median overall survival(MST) were 10.8 months and 10.3 months(P>0.05). Toxicity evaluation: Grade IV serious adverse event did not occur among all enrolled patients. The incidence of nausea and vomiting in the DOF combination with thalidomide group was lower than in the DOF group(P<0.05), but the incidence of constipation was higher than DOF group(P<0.05). The improvement of sleep in the DOF combination group was noticed. There was no statistical difference in other side effects(P>0.05). The short-term efficacy and long-term survival were independent of Gender, age.Conclusion: DOF combination with thalidomide is a more effective and well-tolerated regimen and capable of improving the life quality of patients with advanced gastric cancer. Thalidomide, as a potent agent in improving sleep quality, enhancing the antitumor efficacy and immunity, has a low cost and is well tolerated. Thus, it is worth widely been used in cooperation with DOF regimen in the clinical treatment of advanced gastric cancer. |
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