Impact of Renal Function on S-1 + Radiotherapy for Locally Advanced Pancreatic Cancer: An Integrated Analysis of Data From 2 Clinical Trials

Pancreas. 2021 Aug 1;50(7):965-971. doi: 10.1097/MPA.0000000000001879.

Abstract

Objectives: S-1 monotherapy with concurrent radiotherapy (RT) is a standard of care for patients with locally advanced pancreatic cancer (LAPC). Although renal dysfunction increases S-1 monotherapy toxicity, its effect in S-1 with concurrent RT remains unknown. We evaluated the effect of renal function on the safety of S-1 with RT for LAPC.

Methods: We performed an integrated exploratory post hoc analysis of data from 2 prospective studies (JCOG1106 and LAPC-S1RT), where patients with LAPC received RT (50.4 Gy/28 fraction for 5.5 weeks) and concurrent S-1 (40 mg/m2 per dose, twice daily on the day of irradiation). We split the patients into high creatinine clearance (CCr; ≥80 mL/min) and low CCr (<80 mL/min) groups and compared the findings to determine treatment safety.

Results: The high and low CCr groups showed a median of 97.5 (range, 80.0-194.6) and 64.4 (range, 50.0-78.3) mL/min, respectively. The low CCr group presented more adverse reactions (ARs) of grade 3 or higher and gastrointestinal ARs of grade 2 or higher than the high CCr group (30.8% vs 15.8% and 51.9% vs 36.8%).

Conclusions: The incidence of ARs associated with concurrent S-1 and RT increases in patients with low CCr; therefore, ARs should be duly considered in such patients.

MeSH terms

  • Aged
  • Anorexia / etiology
  • Antimetabolites, Antineoplastic / adverse effects
  • Antimetabolites, Antineoplastic / therapeutic use
  • Chemoradiotherapy / methods
  • Clinical Trials as Topic
  • Drug Combinations
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Kidney / drug effects*
  • Kidney / physiopathology
  • Kidney / radiation effects*
  • Kidney Function Tests / methods
  • Male
  • Middle Aged
  • Nausea / etiology
  • Outcome Assessment, Health Care / methods
  • Outcome Assessment, Health Care / statistics & numerical data
  • Oxonic Acid / adverse effects
  • Oxonic Acid / therapeutic use*
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / therapy*
  • Radiotherapy / adverse effects
  • Radiotherapy / methods*
  • Tegafur / adverse effects
  • Tegafur / therapeutic use*
  • Vomiting / etiology

Substances

  • Antimetabolites, Antineoplastic
  • Drug Combinations
  • S 1 (combination)
  • Tegafur
  • Oxonic Acid