P-070 - Phase I dose-finding study of S-1 in combination with docetaxel and oxaliplatin (DOS) as first-line therapy in patients with advanced gastro-esophag...

Date 04 July 2015
Event WorldGI 2015
Session Posters
Topics Anti-Cancer Agents & Biologic Therapy
Oesophageal Cancer
Gastric Cancer
Presenter P. Pfeiffer
Citation Annals of Oncology (2015) 26 (suppl_4): 1-100. 10.1093/annonc/mdv233
Authors P. Pfeiffer, L. Vestermark, H. Jensen, K. Schoennemann, M. Krogh
  • Odense University Hospital, Odense/DK

Abstract

Introduction

S-1 was developed to provide more efficacious and safer oral delivery of 5-FU (F) or capecitabine. Recently S-1 in combination with cisplatin (C) was approved in Europe for the treatment of advanced gastro-esophageal cancer (aGEC). Addition of docetaxel (D) to F or CF has become a widely used combination for the treatment of aGEC. The present phase I study was designed to establish a recommended dose of the combination of docetaxel + oxaliplatin (O) + S-1 in aGEC.

Methods

Based on our recent phase I study evaluating DOX (Andersen, Acta Oncol 2010 & Schønnemann, Acta Oncol 2011), we only planned 3 dose levels (3 + 3 design). All pts had histologically confirmed GE adenocarcinoma. No pts had received prior chemotherapy. DOS was given with escalating doses of D (40 mg/m2 to 60 mg/m2 day 1), fixed doses of O (100 mg/m2 day 1) and S-1 (2 x 25 mg/m2/days orally day 1-14) every 3 weeks for a maximum of 6 cycles followed by maintenance therapy with S-1 monotherapy (2 x 30 mg/m2/days 1-14) until progression. Toxicity was evaluated according to NCIC-CTC 4.0. DLT was defined as non-hematological toxicity grade ≥ 3 or febrile neutropenia and evaluated after the first course of DOS. Recommended dose (RD) was defined as the highest dose level at which less than < 2/6 of pts experienced a DLT during Cycle 1. Once RD was established, this dose level was expanded to at least 6 pts.

Results

From Oct 2013 to Dec 2014, 15 pts were treated with escalating doses of DOS. Median age was 67 years (49-75); median performance status was 1 (0-1). None of 3 patients at dose level 1 and 2 developed DLT. At dose level 3, 2/4 pts developed DLT (febrile neutropenia and febrile neutropenia with diarrhoea) and further inclusion at dose level 3 was halted. Five further patients at dose level 2 confirmed tolerability of DOS. 7/13 evaluable patients obtained PR; 3 had PD before 6 cycles of DOS; 5 pts continue DOS.

Conclusion

For standard therapy and for further development we recommend DOS at dose level 2 (D 50 mg/m2 day 1; O 100 mg/m2 day 1 and S-1 25 mg/m2 x 2 day 1-14 every 3 weeks). DOS is a well-tolerated first-line regimen in aGEC in an outpatient setting. Clinical trial information: 2011-003471-11.