5-Fluorouracil, Mitomycin-C, and Polysaccharide-K versus Uracil-Ftorafur and Polysaccharide-K as Adjuvant Chemoimmunotherapy for Patients with Locally Advanced Gastric Cancer with Curative Resection

Abstract

Background: Despite the small but significant survival benefit of adjuvant chemotherapy in locally advanced gastric cancer (LAGC), the optimal regimen remains to be determined. We conducted a randomized trial comparing oral (PO) chemoimmunotherapy (CITX) with intravenous (IV) CITX in LAGC patients (stages IB-IIIB) with curative resection (≥ D2 dissection). Methods: The patients were randomized to the IV (5-fluorouracil 500 mg/m² weekly for 24 weeks, mitomycin-C 8 mg/m² every 6 weeks × 4) or the PO (uracil-ftorafur (UFT) 400-600 mg/day for 12 months) group. Patients in both groups received PO polysaccharide-K (3 g/day for 4 months). The planned number of patients was 368 for proving the non-inferiority of PO CITX compared to IV CITX for overall survival. Results: The trial was closed prematurely after enrolling 82 patients (44 in the IV group, 38 in the PO group). With a median follow-up of 82 months, there were no significant differences in the 5-year disease-free survival (73% vs. 55%, p = 0.358) and overall survival (77% vs. 66%, p = 0.159) between the 2 groups. The IV group demonstrated a higher incidence of grade 2 or 3 neutropenia, thrombocytopenia, and vomiting. Conclusions: PO CITX with UFT appeared to be at least non-inferior to 5-fluorouracil and mitomycin-C CITX, with lower toxicity in the adjuvant treatment for LAGC.

Synergistic antitumor effect of puerarin combined with 5-fluorouracil on gastric carcinoma

“…The compound 5-fluorouracil (5-FU) remains a first line antineoplastic treatment in clinical practice ( 4 ). However, GC cells are becoming resistant to existing chemotherapeutic compounds, including 5-FU.…”

Protein-bound polysaccharide K prolonged overall survival in gastric cancer patients from a non-Japanese Asian country who received gastrectomy and adjuvant chemotherapy

“…[7] In addition to intravenous fluorouracil, the efficacy of combining PSK with oral fluoropyrimidines such as tegafur/gimeracil/oteracil (S-1) or uracil-ftorafur (UFT) in operated advanced gastric cancer patients has also been shown in retrospective studies [8][9][10] and in 1 small randomized control trial. [11] However, all of these studies were conducted in a single country (Japan), limited to combinations with fluoropyrimidines, conducted in a retrospective manner, and only enrolled a small number of patients. The treatment effect of the addition of PSK to other adjuvant chemotherapy backbones such as epirubicin, platinum or taxane-based regimens is unknown.…”