Phase I study of neoadjuvant chemoradiotherapy with S-1 for clinically resectable type 4 or large type 3 gastric cancer in elderly patients aged 75 years and older (OGSG1303)

Med Oncol. 2024 Dec 19;42(1):31. doi: 10.1007/s12032-024-02583-3.

Abstract

Purpose The prognosis for type 4 and large type 3 gastric cancer (GC) is extremely poor, especially in elderly patients (≥ 75 years). To improve the prognosis of these types of GC, we performed a phase I study to determine the recommended dose (RD) of S-1 combined with neoadjuvant radiotherapy. Methods Patients with clinically resectable type 4 and large type 3 GC were enrolled to successive cohorts in a conventional 3 + 3 design. Three dose levels were designed, as follows: level 0: S-1 60 mg/m2/day on Days 1-14; level 1: S-1 80 mg/m2/day on Days 1 -14; level 2: S-1 80 mg/m2/day on Days 1-14 and Days 22-35. The starting dose was level 1. Radiotherapy was delivered at a total dose of 40 Gy in fractions for 4 weeks. Results Ten patients were enrolled from July 2014 to August 2018. Six patients were registered at level 1, and one patient developed a dose limiting toxicity as gastric stenosis (grade 3). Two of four patients enrolled at level 2 developed dose limiting toxicity (inability to receive S-1 for hematological reasons). Therefore, the RD was determined as level 1. All patients underwent the protocol surgery; one patient underwent R1 resection because of positive peritoneal washing cytology. There were no treatment-related deaths, and the pathological response rate was 80%. The 5-year overall- and progression-free survival rates were both 60.0%. Conclusion The RD was determined as level 1. A phase II trial using the RD should be initiated.

Keywords: Chemoradiotherapy; Elderly; Gastric cancer; Large Type 3; S-1; Type 4.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antimetabolites, Antineoplastic / therapeutic use
  • Chemoradiotherapy / methods
  • Drug Combinations*
  • Female
  • Humans
  • Male
  • Neoadjuvant Therapy* / methods
  • Oxonic Acid* / administration & dosage
  • Oxonic Acid* / therapeutic use
  • Stomach Neoplasms* / mortality
  • Stomach Neoplasms* / pathology
  • Stomach Neoplasms* / therapy
  • Tegafur* / administration & dosage
  • Tegafur* / adverse effects
  • Tegafur* / therapeutic use

Substances

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