568P - Safety and efficacy of intravenous cetuximab (CET) and hepatic artery infusion of irinotecan, 5-fluorouracil and oxaliplatin in patients with unrese...

Date 01 October 2012
Event ESMO Congress 2012
Session Poster presentation III
Topics Anti-Cancer Agents & Biologic Therapy
Colon Cancer
Rectal Cancer
Presenter Francis Levi
Authors F. Levi1, V. Boige2, P. Rougier3, M. Hebbar4, D. Smith5, C. Focan6, R. Guimbaud7, C. Carvalho8, M. Bouchahda9, M. Ducreux2
  • 1Inserm U776 Rythmes Biologiques Et Cancers (campus Cnrs, 7 Rue Guy Moquet), Paul Brousse Hospital, 94800 - VILLEJUIF/FR
  • 2Oncologie Digestive, Institut de Cancérologie Gustave Roussy, 94805 - Villejuif/FR
  • 3Digestive Oncology, Hopital European George Pompidou, 75015 - Paris/FR
  • 4Department: Unité D'oncologie Médicale, CHRU DE LILLE - Hôpital Huriez, 59037 - LILLE/FR
  • 5Oncologie Digestive, Hôpital Saint André, 33000 - Bordeaux/FR
  • 6Département D'oncologie, CHC-Clinique Saint-Joseph, B-4000 - LIEGE/BE
  • 7Oncologie Médicale, CHU Toulouse Purpan, 31059 - Toulouse cedex 9/FR
  • 8Unidade De Oncologia, Hospital Prof. Doutor Fernando Fonseca, 2720-276 - Amadora/PT
  • 9Chronotherapy Unit, Medical Oncology Department, Inserm, U776, Paul Brousse Hospital, 94800 - VILLEJUIF/FR

Abstract

Background

Hepatic artery infusion (HAI) of chronomodulated (Chrono) irinotecan (I), 5-Fluorouracil (F) and oxaliplatin (O), or flat O combined with intravenous (iv) F-Leucovorin allowed secondary metastases resections and prolonged survival in patients (pts) with CRC liver metastases despite prior failure of iv chemotherapy (Bouchahda, Cancer 2009; Goere, Ann Surg 2010).

Purpose

To prospectively evaluate safety and efficacy of combining iv Cet with HAI of IFO in pts with CRC liver metastases.

Methods

This Phase II trial involved pretreated pts with unresectable CRC liver metastases receiving iv Cet (500 mg/m2) and Chrono or Conventional (Conv) HAI of I (180 mg/m2), F (2800 mg/m2), and O (85 mg/m2) q2 weeks. Liver metastases were resected whenever adequately downstaged.

Results

Accrual of 64 pts (42 M, 22F; age, 33-76 years; 4 ongoing) was complete at 9 centers (4 countries) on 13/03/2012. In 62 monitored pts: PS 0/1/2 (61/36/3%), bilobar liver lesions (84%), a median of 9 metastases (1-50; largest diameter, 54 mm; range, 15-172) involving a median of 6 segments (1-8). Pts received one (44%), two (30%) or three (26%) prior iv chemotherapy lines. A median of 5 courses (1-13) was given to 59 pts (Chrono, 18; Conv, 41; 3 never treated), with artery occlusion as main cause of withdrawal (53%). Main grade 3-4 toxicities per pt were neutropenia (39%), abdominal pain (25%), fatigue (17%), diarrhea (15%), and nausea (10%). Grade 3 sensory neuropathy occurred in 3% of the pts. Intent-to-treat objective tumor response rate was 45% [95% CL,31-59], including 2 radiological complete responses. Disease control rate was 83%. Per-protocol secondary liver surgery rate was 33.3% [20.4-46.2]. One pt had pathologic complete response in 24/25 metastases in all liver segments (1-6 cm) and has been disease-free for 25+ months and alive at 38+ months. Median progression-free survival (41 events) was 9.1 months [6.5-11.6]. Preliminary median survival (19 events) is 28.6 months [16.3-40.9].

Conclusions

The combination of intravenous cetuximab with triplet HAI chemotherapy offers a safe and highly effective treatment option for patients with chemotherapy- refractory CRC liver metastases. Support: ARTBC International, Villejuif; Merck-Serono & Pfizer (France).

Disclosure

All authors have declared no conflicts of interest.