P-0224 - Four-year survival rate after second line conversion treatment to hepatic resection using triplet hepatic artery infusion and intravenous cetuximab...

Date 28 June 2014
Event World GI 2014
Session Poster Session
Topics Anti-Cancer Agents & Biologic Therapy
Colon Cancer
Rectal Cancer
Surgery and/or Radiotherapy of Cancer
Presenter Francis Lévi
Citation Annals of Oncology (2014) 25 (suppl_2): ii14-ii104. 10.1093/annonc/mdu165
Authors F. Lévi1, D. Castaing2, V. Boige3, P. Rougier4, R. Adam5, M. Bouchahda1, A. Karaboué6, M. Hebbar7, C. Lepère8, C. Focan9, R. Guimbaud10, P. Innominato1, C. Carvalho11, S. Tumolo12, S. Truant7
  • 1INSERM UMR 776, Medical Oncology Unit, Paul Brousse Hospital, Villejuif/FR
  • 2Hepato-Biliary centre, Hôpital Paul Brousse, Villejuif/FR
  • 3Institut Gustave Roussy, Villejuif/FR
  • 4Hopital Europeen Georges Pompidou, Paris/FR
  • 5AP-HP Hôpital Paul Brousse, Villejuif/FR
  • 6INSERM UMR 776, Paul Brousse Hospital, Villejuif/FR
  • 7Medical Oncology Unit - Hôpital Huriez, Lille/FR
  • 8Hôpital Européen Georges Pompidou, Paris/FR
  • 9Département d'Oncologie, CHC Clinique Saint Joseph, Liège/BE
  • 10Service de Gastroentérologie, Hôpital Rangueil, Toulouse /FR
  • 11Medical Oncology Unit, Hospital Fernando Fonseca, Amadora/PT
  • 12UO Oncologia - Azienda Ospedaliera S.Maria degli Angeli - Pordenone, Pordenone/IT



Less than 15% of the patients (pts) with previously unresectable colorectal cancer (CRC) liver metastases (LM) and prior chemotherapy undergo successful complete macroscopic LM resection (R0-R1). Here, we determine Overall Survival (OS) in pts undergoing R0-R1 partial hepatectomy after second line hepatic artery infusion (HAI) with Irinotecan, 5-Fluorouracil and Oxaliplatin (IFO), and intravenous cetuximab (IV-CET) for LM-CRC in the first multicenter European trial testing this strategy.


Nine centers in 4 countries accrued 64 pts with unresectable LM-CRC after failure of 1-3 prior chemotherapy protocols. Pts had bilateral LM (84% pts), a median number of 10 LM, with a median largest diameter of 53 mm, and tumor spread in a median number of 6 segments. Liver surgery was performed whenever R0-R1 became feasible according to imaging review at q6-9 weeks multidisciplinary review. Data were analyzed after 4 years follow-up.


The OPTILIV regimen was given as 2nd line chemotherapy protocol to 28/64 registered pts (44%), including 11F and 17M, aged 33-75 years, with good PS (0-1: 100%). The 28 pts had a median of 10 LM (1-69), whose largest diameter was 41 mm (15-142). LM were bilateral for 24 pts (96%) and involved, a median of 6 segments (1-8). Objective response rate was 35.7% [95%CL, 18.0-53.4]. R0-R1 hepatectomy was performed in 13/28 pts (46.4%) 3-19 months (mo) after inclusion (median, 5 mo). Pts who underwent liver surgery tended to have less extensive liver involvement (≤25% tumor replacement: 10/13 pts vs 5/15 pts; p = 0.030; median number of liver segments involved: 4 (1-8) vs 7 (2-8); p = 0.013). Main grade 3-4 toxicities per pt were similar in both groups (neutropenia, 46.2% vs 40.0%; abdominal pain, 15.4% vs 13.3%). After a maximum follow up of 52 months (mo.), median overall survival time was 28.6 mo [22.9-34.3] for the non-resected pts and it was not reached in the pts with R0-R1 hepatectomy following conversion to resectability on OPTILIV (p = 0.003). The estimated 4-year survival rates were 0% for the non resected pts and 87.5% [95%CL 75.3-99.8] for the resected ones (p = 0.003).


The combination of IV-CET with HAI-IFO as 2nd line chemotherapy for metastatic colorectal cancer with predominant and initially unresectable LM converted nearly half of the pts to R0-R1 hepatectomy, with ∼90% of the resected pts alive beyond 4 years. Both conventional and chronomodulated OPTILIV regimens deserve upfront testing as potential most effective options for the eradication of LM-CRC through a curative intent medico-surgical strategy.