2891 - A phase I study of Docetaxel/Oxaliplatin/S-1 (DOS) combination neoadjuvant chemotherapy for patients with locally advanced adenocarcinoma of the esophagogastric junction

Background

A triple chemotherapeutic regimen including docetaxel, oxaliplatin, and S-1 (DOS) for a neoadjuvant setting has a promising efficacy for locally advanced adenocarcinoma of the esophagogastric junction (AEG). However, the optimal dose of each drug in Japanese population remained to be clarified. The aim of this phase I study is to determine a recommended dose for a triweekly combination neoadjuvant DOS chemotherapy for patients with locally advanced AEG.

Methods

Patients with cT3 or more advanced AEG without distant metastasis were eligible for this study. The planned dosages of docetaxel (mg/m², day 1), oxaliplatin (mg/m², day 1), and S-1 (mg/day, days 1–14) were 50/100/80–120 at level 1, and 60/100/80–120 at level 2. The treatment cycle was repeated every 3 weeks, and patients were assessed for response to the treatment after 2 and 3 cycles. This study was registered with UMIN Clinical Trial Registry (UMIN 000022210).

Results

Twelve patients with locally advanced AEG were enrolled in this study. At dose level 1, one of six patients experienced dose-limiting toxicity (DLT) of grade 3 febrile neutropenia. At dose level 2, two of the next six patients experienced the same DLT of need for withdrawal of chemotherapy due to serious adverse events. Based on these results, level 2 was considered the recommended dose for this regimen. Total or proximal gastrectomy plus lower esophagectomy, or subtotal esophagectomy was performed in all the 12 patients with the R0 resection rate of 92% (11/12). Histological response evaluation based on the classification defined by Japanese Gastric Cancer Association revealed four patients with grade 1a, two with grade 1b, three with grade 2, and three with Grade 3.

Conclusions

Recommended doses for a neoadjuvant DOS chemotherapy regimen for locally advanced AEG were determined as Docetaxel: 60 mg/m², Oxaliplatin: 100 mg/m² on day 1, S-1: <1.25m², 80 mg; 1.25–1.5m², 100 mg; >1.5m², 120 mg twice a day on days 1–14. DOS chemotherapy showed good preliminary efficacy with acceptable toxicity in this study warranting a further phase II trial to investigate the efficacy of the DOS regimen.

Clinical trial identification

UMIN 000022210.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.