Phase I trial of hepatic arterial infusion (HAI) with floxuridine (FUDR) and dexamethasone (DEX) in combination with systemic oxaliplatin (OXAL), fluorouracil (FU) + leucovorin (LV) after resection of hepatic metastases from colorectal cancer

Abstract

3579 Background: Our earlier studies using HAI plus SYS chemotherapy after liver resection demonstrated significant decrease in hepatic recurrence. In order to decrease extrahepatic recurrence in resected patients (pts), combinations of HAI and new SYS therapies are needed. We designed a Phase I trial of HAI FUDR + DEX and SYS OXAL, FU + LV. Methods: OXAL was kept constant (85mg/m2) while FU was escalated: 1000–1400 mg/m2 (48-hour infusion). Then OXAL was escalated (100 mg/m2) and FU from 1400–1800 mg/m2. LV was fixed at 400 mg/m2. HAI FUDR dose was fixed at 0.12 mg/kg x pump volume (PV) divided by pump flow rate (PF), and infused Day (D) 1–14 with DEX, heparin and saline. SYS therapy was given on D14 and D28 of a five-week cycle. Results: 21 pts have been enrolled: median age 58 (range 41 -74); margin of resection ≤ 0.3 cm (28%); number of lesions ≥ 2 (71%); synchronous disease (38%); received previous chemotherapy (71%). Dose-limiting toxicity (DLT) was reached when FU was 1800mg/m2 and OXAL 100mg/m2, with Gr 3 diarrhea and fatigue. This dose of OXAL compromised HAI FUDR administration (see table below). Median follow-up is 20.5 months. Three pts [2 lung and 1 liver] progressed at 6, 16, and 7 months; median is not reached. One-year disease-free rate is 88% (95% CI, 73–100). One-year survival is 100%; median is not reached. Conclusion: The MTD of combined HAI + SYS is FUDR 0.12mg/kg x PV/PF, plus systemic OX at 85 mg/m2 and 5FU at 1600 mg/m2. It is too early to determine whether there is a decrease in the occurrence of lung mets, but survival data is encouraging. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Sanofi