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]

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Summary

Introduction

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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