Gemcitabine plus S-1: a hopeful frontline treatment for Asian patients with unresectable advanced pancreatic cancer

Abstract

Objective: Gemcitabine-based chemotherapy is widely used for unresectable advanced pancreatic cancer which contains locally advanced and metastatic pancreatic cancer. We performed metaanalysis to examine whether gemcitabine plus S-1 could improve treatment efficacy as first-line chemotherapy for those patients when compared with gemcitabine alone. Methods: STATA was used to estimate the summary hazard ratios or odds ratios and their 95% confidence intervals. Heterogeneity among trials was examined by Cochran's χ 2 test. Publication bias was evaluated by Begg's and Egger's tests. Subgroup analysis based on the extent of disease was performed.Results: Four randomized controlled trials including 878 Asian patients were analyzed. In total metaanalysis, gemcitabine plus S-1 significantly improved overall survival (hazard ratio, 0.82; 95% confidence interval, 0.70-0.96; P = 0.015), progression-free survival (hazard ratio, 0.64; 95% confidence interval, 0.55-0.74; P < 0.001), overall response rate (odds ratio, 3.00; 95% confidence interval, 2.04-4.41; P < 0.001) and disease control rate (odds ratio, 1.78; 95% confidence interval, 1.32 to 2.39; P < 0.001), and was associated with more but manageable hematologic (leukocytopenia, neutropenia, thrombocytopenia) and non-hematologic (diarrhea, stomatitis, nausea, rash) adverse events. In subgroup analysis, gemcitabine plus S-1, comparing with gemcitabine, significantly improved overall survival in locally advanced patients (hazard ratio, 0.69; 95% confidence interval, 0.48 to 0.99; P = 0.022) but not in metastatic patients (hazard ratio, 0.75; 95% confidence interval, 0.46-1.23; P = 0.256).Conclusion: This meta-analysis confirmed the survival benefits of gemcitabine plus S-1 as first-line treatment for unresectable advanced pancreatic cancer at least in Asia, while good Eastern Cooperative Oncology group performance status was warranted. Importantly, we highlighted the significant overall survival benefit of gemcitabine plus S-1 in locally advanced patients but not in metastatic patients.

Who could complete and benefit from the adjuvant chemotherapy regarding pancreatic ductal adenocarcinoma? A multivariate‐adjusted analysis at the pre‐adjuvant chemotherapy timing

“…All PDAC patients undergoing radical surgeries should be treated with adjuvant chemotherapy, which is vital to cure the disease and prolong survival. Gemcap is the guideline‐recommended regimen, 3,22 and GS is an alternative regimen designed for Asian patients 23–27 . As shown in Figure 1, the CHC was higher in the Gem and GS groups, which represented better chemotherapy tolerance.…”

Pathological complete response in a patient with locally advanced pancreatic adenocarcinoma treated with neoadjuvant gemcitabine and S-1: a case report and literature review

“…Additionally, the most common adverse event was fatigue (86%) and grade 3 events only occurred in 3% of patients. Cao et al performed a metaanalysis including 4 RCTs to examine the efficacy of GS-1, and results showed a significant OS improvement in locally advanced patients but not in metastatic patients, which suggested its disadvantage in metastatic cases (17).…”

Gemcitabine and S-1 Induction Chemotherapy Followed by Chemoradiotherapy for Locally Advanced Pancreatic Cancers

“…Several meta-analysis studies indicate that GEM/S-1 combination therapy, as a first-line treatment, may be more effective at increasing survival rates in patients with unresectable pancreatic cancer (5,24). Qing-Hua et al showed that GEM/S-1 combination therapy followed by oral S-1 with intensity-modulated radiotherapy (IMRT) protocol achieved a 2-year survival rate of 34.4%, which was similar to the results we have outlined in this study (2-year survival rate of 33.3%) (11).…”

“…CRT is now generally accepted as standard treatment for locally advanced pancreatic cancer (LAPC) (3,4). A combination chemotherapy using gemcitabine and fluorouracil drugs, such as S-1, is considered to be one of the more promising treatment regimens for unresectable pancreatic cancer (5,6). In contrast, the exact role of CRT in combination therapy is not well understood yet, especially when compared to monochemotherapy.…”