Chronomodulated Hepatic Artery Infusion (Hai) Of Irinotecan, 5-Fluorouracil (5-Fu), And Oxaliplatin (L-Ohp) Plus Intravenous (Iv) Cetuximab (Cet) (Chrono-Optiliv) In Patients With Unresectable Liver Metastases From Wt Kras Colorectal Cancer (Lm-Crc) After Treatment Failure (European Phase Ii Trial Nct 00852228)

3606 Background: Hepatic artery triplet chronotherapy is an effective salvage therapy for pretreated LM-CRC (Bouchahda et al. Cancer 2009). The combination of iv Cet with chrono or conventional triplet HAI allowed complete macroscopic resection (R0-R1) of previously unresectable LM-CRC in 28% of the pts, and median progression-free (PFS) and overall survival (OS) of 8.7 and 25.7 months respectively, despite prior chemotherapy (Levi et al. ASCO-GI 2013). Purpose: To relate tolerability and efficacy of Chrono-Optiliv to pharmacokinetics (PK). Methods: 18/64 registered patients received iv Cet (500 mg/m²) and chrono HAI of Irinotecan (180 mg/m²), 5-FU (2800 mg/m²), and l-OHP (85 mg/m²) q2 weeks. Liver surgery was performed according to q6wks reviews. The systemic exposure to the 4 drugs was determined on 1st course in 11 pts, through 16 samples over 56h. Results: 8F, 10M, aged 33-72 years had good PS (0/1: 83%/17%), a median of 7 LM-CRC (2-50) in 6 segments (1-8) with median largest diameter of 47 mm (15-130...