Modified gemcitabine, S-1, and leucovorin combination for patients with newly diagnosed locally advanced or metastatic pancreatic adenocarcinoma: A multi-center retrospective study in Taiwan

PLoS One. 2020 Dec 29;15(12):e0244487. doi: 10.1371/journal.pone.0244487. eCollection 2020.

Abstract

Background: 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.

Methods: 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.

Results: 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%).

Conclusions: 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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives
  • Disease Progression
  • Drug Combinations
  • Feasibility Studies
  • Female
  • Follow-Up Studies
  • Gemcitabine
  • Humans
  • Intention to Treat Analysis
  • Leucovorin / administration & dosage
  • Leucovorin / adverse effects
  • Male
  • Middle Aged
  • Oxonic Acid / administration & dosage
  • Oxonic Acid / adverse effects
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / secondary
  • Progression-Free Survival
  • Retrospective Studies
  • Taiwan / epidemiology
  • Tegafur / administration & dosage
  • Tegafur / adverse effects
  • Treatment Failure

Substances

  • Drug Combinations
  • Deoxycytidine
  • S 1 (combination)
  • Tegafur
  • Oxonic Acid
  • Leucovorin
  • Gemcitabine

Grants and funding

LYB: grants from the National Health Research Institutes, Taiwan (NHRI-109A1-CACO-13202002), the Ministry of Health and Welfare, Taiwan (MOHW109-TDU-B-212-134026), and Ministry of Science and Technology, Taiwan (MOST109-2321-8-006-011-) during the study. CFC: grants from the Ministry of Health and Welfare, Taiwan (MOHW109-TDU-B-212-010001).