Purpose: The prognosis of diffuse-type gastric cancer (DGC) is poorer than that of intestinal type, but S-1 is a potential treatment option in DGC. This study explored the maximal tolerated dose (MTD) and the recommended dose for phase II study (RP2D) of nab-paclitaxel combined with S-1 (AS regimen) as adjuvant chemotherapy in stage III DGC.
Methods: Patients with stage III DGC were recruited into this phase I dose-escalation study between July 2019 and June 2020 in Zhongshan Hospital. Nab-paclitaxel and S-1 (80-120 mg/day, d1-14, q3w) were administrated for 6 cycles, and then 8 cycles of S-1 monotherapy were applied. The patients received nab-paclitaxel at 180, 220, or 260 mg/m2 according to the 3 + 3 design based on dose-limiting toxicity (DLT). The primary endpoint was RP2D. Secondary endpoints were the 1-year disease-free survival (DFS) rate and adverse events (AEs).
Results: One case experienced DLT in 180-mg/m2 dose group, subsequently three additional subjects were enrolled. DLT was not observed in the 220- and 260-mg/m2 dose groups (both n = 3). Therefore, the MTD has not reached, and the RP2D of nab-paclitaxel would be 260 mg/m2 . Five participants showed progressive disease, with three and two participants in the 180- and 220-mg/m2 dose groups, respectively. The 6-, 12-, and 18-month DFS rates were 100%, 63.6%, and 50.9%, respectively. The most frequently observed AEs were neutropenia (83.3%) and leukopenia (66.7%).
Conclusion: The RP2D of nab-paclitaxel as adjuvant chemotherapy in DGC was 260 mg/m2 . The AS regimen had a tolerable AE profile in stage III DGC.
Trial registration: ClinicalTrials.gov NCT03977220.
Keywords: S-1; gastric cancer; maximal tolerated dose; nab-paclitaxel; phase I.
© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.