Preliminary Results Of A Randomized Phase Ii Trial Comparing Standard Bi-Therapy Versus Three Intensified Chemotherapy Regimens As Treatment For Patients With Non Resectable Liver Metastases From Colorectal Cancer (Lmcrc). (Methep)

4075 Background: LVFU combinations with irinotecan (FOLFIRI) or oxaliplatin (FOLFOX) have shown to improve outcome of advanced colorectal cancer. However, the standard doses of these regimens applied to patients with initially unresectable LMCRC have shown poor rates of resectability. The aim of this randomized trial was to select the most efficacious experimental intensified chemotherapy arm among high dose (HD) FOLFIRI (Iri 260mg/m²), FOLFOX-7 (Ox 130mg/m²) and FOLFIRINOX (Iri 180mg/m² + Ox 85mg/m²) in patients (pts) with initially unresectable or potentially resectable LMCRC. Methods: Main inclusion criteria: non pretreated potentially resectable LM (class II) or unresectable LM without extra-hepatic metastases except 1 to 3 resectable lung metastases. Pts were randomized to either standard (A/B) or intensified chemotherapy (C/D/E): FOLFIRI (A), FOLFOX-4 (B), FOLFIRI-HD (C), FOLFOX-7 (D), or FOLFIRINOX (E). In arms C/D/E, prophylactic G-CSF was given. Primary endpoint was objective response rate (RR) (RECIST) after Cycle 4. Secondary endpoints were safety, R0 surgical resection, best RR, PFS and OS. A total of 120 pts randomized in a 1:1:2:2:2 ratio were necessary to select an experimental arm (2-stage Fleming design, p0=0.40, p1=0.60, alpha=10%, beta=20%). Results: Between Oct 2004 and Aug 2007, 125 pts from 17 centers were randomized, 122 were eligible and treated: 30 (A+B), 32 (C), 30 (D) and 30 (E). Reasons for unresectability were well balanced: 45% pts had less than 30% of remaining healthy liver, 20% had vascular contact, and 35% were class II. Respectively 20, 12, 23 and 17% had lung metastases in arms (A+B), C, D and E. Grade 3/4 toxicities during the first 4 cycles in Arms (A+B)/C/D/E were respectively: neutropenia (24, 19, 10, 23%) diarrhea (0, 6, 3, 23%), mucositis (0, 3, 0, 7%), vomiting (7, 9, 0, 3%), neurotoxicity (0, 0, 10, 3%). The objective RR after 4 cycles in Arms (A+B)/C/D/E were: 43, 50, 50 and 52%. Conclusions: These results suggest an improvement in early RR for LMCRC with these intensified chemotherapy regimen with acceptable toxicity. Major secondary endpoints such as R0 surgical resection will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer Oncology, sanofi-aventis sanofi-aventis