580P - Hepatic arterial infusion (HAI) of oxaliplatin plus intravenous (IV) fluorouracil (FU), leucovorin (LV) and cetuximab for first-line treatment of un...

Date 01 October 2012
Event ESMO Congress 2012
Session Poster presentation III
Topics Anti-Cancer Agents & Biologic Therapy
Colon Cancer
Rectal Cancer
Presenter David Malka
Authors D. Malka1, V. Boige2, M. Faron3, C. Caramella4, E. Boucher5, P. Rivera6, T. de Baere4, D. Goéré7, J. Pignon3, M. Ducreux2
  • 1Oncology, Institut Gustave Roussy, 94805 - Villejuif/FR
  • 2Oncologic Medicine, Institut Gustave Roussy, 94805 - Villejuif/FR
  • 3Biostatistics And Epidemiology, Institut Gustave Roussy, Villejuif/FR
  • 4Radiology, Institut Gustave Roussy, Villejuif/FR
  • 5Medical Oncology, Centre Eugène Marquis, Rennes/FR
  • 6Medical Oncology, CHU, Toulouse/FR
  • 7Surgery, Institut Gustave Roussy, Villejuif/FR

Abstract

Background

To determine the efficacy and tolerance of HAI oxaliplatin plus iv FU/LV and cetuximab in patients (pts) with unresectable CRLM.

Methods

Main eligibility criteria for this phase 2 study were: histologically proven colorectal adenocarcinoma; tumor wild-type (wt) KRAS status (protocol amendment in 09/2008); unresectable CRLM; no extrahepatic disease (except primary with absent/mild symptoms, and ≤ 3 nonspecific lung nodules ≤ 5 mm in diameter); no prior chemotherapy for metastatic disease; WHO performance status 0-1. After surgical or percutaneous insertion of an implantable HAI catheter, pts were treated with HAI oxaliplatin (100 mg/m2 in 2 hrs) plus iv modified LV5FU2 regimen (LV, 400 mg/m2 in 2 hrs; FU, 400 mg/m2 bolus then 2400 mg/m2 in 46 hrs) every two weeks plus iv cetuximab (400 mg/m2 then 250 mg/m2/week, or 500 mg/m2 every two weeks) until disease progression, limiting toxicity, or CRLM resection. Primary endpoint was objective response rate (ORR) (RECIST 1.0). Secondary endpoints included toxicity (NCI CTC-AE v3.0), disease control rate (DCR), resection rate, progression-free survival (PFS), and overall survival (OS).

Results

A total of 36 pts were included in 8 centers from 11/2006 to 12/2009. Most of the 35 eligible pts (male, 63%; median age, 54 yrs [range, 33-75]) had extensive disease (≥ 4 CRLM, 88%; bilobar CRLM, 91%). Pts received a median of 10 cycles (range, 1-41). Main severe toxicity was abdominal pain (40%), neutropenia (37%), peripheral neuropathy (34%) and rash (29%). Among 32 evaluable pts, ORR was 87% and DCR was 97%. Among the evaluable pts with wt KRAS (n = 27) or wt KRAS/BRAF (n = 24) tumor status, ORR were 89% and 96% and DCR 96% and 100%, respectively. Overall, 23 of the 35 pts (66%) underwent curative-intent resection and/or radiofrequency ablation (wt KRAS pts, 21 [70%]; wt KRAS/BRAF pts, 20 [74%]). After a median follow-up of 48 months, median PFS was 29 months (median OS, not reached).

Conclusions

First-line HAI oxaliplatin plus iv LV5FU2 and cetuximab seems feasible and highly effective in pts with unresectable CRLM.

Disclosure

D. Malka: Membership on an advisory board: Roche Research funding: Amgen, Merck Serono, Sanofi-Aventis.

M. Ducreux: Membership on an advisory board: Roche, Pfizer, Sanofi-Aventis, Merck Serono, Amgen Research funding: Roche, Merck Serono, Pfizer.

All other authors have declared no conflicts of interest.