582P - A phase II study of combined cetuximab, irinotecan, oxaliplatin and UFT (ESCOUT) in patients with advanced colorectal cancer (aCRC) incorporating an...

Date 01 October 2012
Event ESMO Congress 2012
Session Poster presentation III
Topics Colon Cancer
Rectal Cancer
Translational Research
Presenter Matthew Krebs
Authors M. Krebs1, S. Gollins2, I. Chau3, J. Hasan4, M. Braun5, K. Morris1, J. Beech5, G. Adaway5, C. Dive1, M. Saunders5
  • 1Clinical And Experimental Pharmacology Group, Paterson Institute for Cancer Research, M20 4BX - Manchester/UK
  • 2North Wales Cancer Treatment Centre, Wales/UK
  • 3Medicine, Royal Marsden Hospital, Sutton/UK
  • 4Medical Oncology, The Christie NHS Foundation Trust, M20 4BX - Manchester/UK
  • 5Medical Oncology, The Christie NHS Foundation Trust, GB-M20 4BX - Manchester/UK

Abstract

Introduction

Patients (pts) with ≥3 CTCs/7.5ml blood at baseline, enumerated by the CellSearch® (Veridex) system, have poor overall survival (OS)1. CTC guided treatment strategies may improve pt outcomes. This study investigated the efficacy of combining 4 active agents and evaluated CTC numbers for prognostic and pharmacodynamic utility.

Methods

Pts with previously untreated, inoperable, ACRC and wtKRAS were eligible. Chemotherapy was administered every 28 days with Cetuximab 400 mg/m2 D1 & D15 and UFT 250 mg/m2 with calcium folinate 30mg TDS D1-21. UFT dose was reduced by 1 caps/day for grade 2/3 diarrhoea. Irinotecan 180 mg/m2 D1 and oxaliplatin 100 mg/m2 D15 alternated to reduce long-term toxicity of each drug. Treatment was continued until disease progression. The primary end-point was response rate (RR) and secondary endpoints included progression free survival (PFS), OS, toxicity and CTC number. Blood samples (7.5ml) for CTC analysis were drawn at baseline and D15. CTCs were enumerated using the CellSearch® system. Results: Forty-eight pts were recruited; 46 were evaluable for response and 42 for CTC enumeration. A 67% RR was achieved with disease control in 91% - CR 2 pts (4%), PR 29 (63%) & SD in 11pts (24%). Two pts with inoperable colonic tumours had curative resections after chemotherapy; no patients had liver only disease. Grade 3 toxicities included diarrhoea (21%), lethargy (17%), neutropenia (8%), parasthesia (17% G2, no G3) and alopecia (4% G2). Only 14 pts have died so OS is expected to increase with longer review. At baseline 50% pts had ≥3 CTCs suggesting this cohort comprised a poor prognostic group; median PFS/OS of these pts was 8.5/18.8 months(m), considerably better than expected (cf 6.1/11.6m in Cohen1). Pts with <3 CTCs at baseline had PFS/OS of 8.8/20.9m. CTCs decreased on treatment in responding pts. Conclusion: The eSCOUT regimen is efficacious with a high RR (67%) and good OS (at least 20.9m). Outcome for pts with ≥3 CTCs was particularly good suggesting intensive chemotherapy may benefit this group. A randomised trial is needed to confirm the results of this phase II study. 1Cohen et al, Ann Oncol, 20:1223; 2009.

Disclosure

All authors have declared no conflicts of interest.