Abstract
In pancreatic cancer, toxicities associated with current chemotherapeutic regimens remain concerning. A modified combination of gemcitabine, S-1, and leucovorin (GSL) was used as the first-line treatment for newly diagnosed locally advanced or metastatic pancreatic adenocarcinoma patients. GSL was administered every 2 weeks-intravenous gemcitabine 800 mg/m2 at a fixed-dose rate of 10 mg/m2/min on day 1 and oral S-1 (80-120 mg/day) plus leucovorin 30 mg twice daily on days 1-7. We retrospectively analyzed the feasibility of GSL and patient outcomes in three medical centers in Taiwan. Overall, 49 patients received GSL with a median follow-up of 24.9 months from May 2015 to March 2019. The median patient age was 68 years (range, 47-83 years), with a marginally higher number of females (57.1%). Among the 44 patients who underwent image evaluation, 13 demonstrated a partial response (29.5%) and 17 presented with stable disease (38.6%). The partial response rate and stable disease rate was 26.5% and 34.7%, respectively, in the intent-to-treat analysis. The median time-to-treatment failure was 5.79 months (95% C.I., 2.63-8.94), progression-free survival was 6.94 months (95% C.I., 5.55-8.33), and overall survival time was 11.53 months (95% C.I., 9.94-13.13). For GSL treatment, the most common grade 3 or worse toxicities were anemia (18.3%), neutropenia (6.1%), nausea (4.1%), and mucositis (4.1%). Treatment discontinuation was mostly due to disease progression (65.3%). The modified GSL therapy can be a promising and affordable treatment for patients with advanced and metastatic pancreatic cancer in Taiwan. A prospective trial of modified GSL for elderly patients is currently ongoing in Taiwan.
Highlights
Pancreatic cancer is an aggressive and lethal cancer owing to its late presentation and resistance to chemotherapy
There is a clear benefit in using these combinations over gemcitabine alone, the prognosis of patients with advanced or metastatic pancreatic cancer remains poor, with a median overall survival of 8 to 11 months and an estimated 2-year survival of only 2%
Filgrastim was allowed for high-risk patients, the incidence of grade 3 or 4 neutropenia and fatigue was reportedly 45.7% and 23.6% in patients treated with FOLFIRINOX, respectively [2]
Summary
Pancreatic cancer is an aggressive and lethal cancer owing to its late presentation and resistance to chemotherapy. There is a clear benefit in using these combinations over gemcitabine alone, the prognosis of patients with advanced or metastatic pancreatic cancer remains poor, with a median overall survival of 8 to 11 months and an estimated 2-year survival of only 2%. In the MPACT trial using nabpaclitaxel plus gemcitabine, the incidence of grade 3 or 4 neutropenia, fatigue, and peripheral neuropathy was 38%, 17%, and 17%, respectively [3]. The combination of nab-paclitaxel and gemcitabine appeared less toxic, this regimen was not reimbursed by Taiwan’s National Health Insurance before 2020. This situation implies an unmet medical need to provide a feasible and affordable therapeutic option for patients with pancreatic cancer in Taiwan. A modified combination of gemcitabine, S-1, and leucovorin (GSL) was used as the first-line treatment for newly diagnosed locally advanced or metastatic pancreatic adenocarcinoma patients
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