Alice Boilève1, Astrid De Cuyper2, Alicia Larive3, Linda Mahjoubi4, Milan Najdawi4, Mélodie Tazdait5, Maximiliano Gelli6, Lambros Tselikas7, Cristina Smolenschi4, David Malka4, Jean-Pierre Pignon8, Michel Ducreux9, Valérie Boige4. 1. Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif, France. Electronic address: alice.boileve@gmail.com. 2. Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif, France; Department of Medical Oncology, Cliniques Universitaires Saint-Luc, Brussels, Belgium. 3. Department of Biostatistics and Epidemiology, Gustave Roussy, University Paris-Saclay, Villejuif, France. 4. Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif, France. 5. Department of Radiology, Gustave Roussy Cancer Campus, Villejuif, France. 6. Department of Surgery, Gustave Roussy Cancer Campus, Villejuif, France. 7. Department of Interventional Radiology, Gustave Roussy Cancer Campus, Villejuif, France. 8. Department of Biostatistics and Epidemiology, Gustave Roussy, University Paris-Saclay, Villejuif, France; Oncostat U1018, Inserm, University Paris-Saclay, Labeled Ligue Contre le Cancer, Villejuif, France. 9. Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif, France; Paris-Saclay University, Villejuif, France.
Abstract
BACKGROUND: Hepatic arterial infusion (HAI) combined with systemic chemotherapy has shown promising results in patients with unresectable colorectal liver metastases (CRLM), even after failure to systemic therapy. Addition of systemic targeted therapies has been investigated with controversial results regarding tolerance, especially with HAI-floruxidine when combined with systemic bevacizumab. Our study aimed to analyse feasibility, safety and efficacy of HAI-oxaliplatin plus systemic chemotherapy and targeted therapies. METHODS: Between 2005 and 2016, single-centre consecutive patients with unresectable CRLM who received at least one cycle of HAI-oxaliplatin plus systemic chemotherapy and targeted therapies (cetuximab/panitumumab or bevacizumab) were analysed. RESULTS: A total of 89 patients (median age 55 years (range, 26-76 years) who previously received a median number of one systemic chemotherapy regimen (range, 0-5) including oxaliplatin in 78% of cases were included. Median number of HAI-oxaliplatin cycles was 9 (range, 1-28) combined with systemic chemotherapy and targeted therapies (LV5FU2 [63%], FOLFIRI [36%]) plus anti-EGFR (30%), or bevacizumab (70%). Grade 3/4 toxicities included neutropenia (40%), HAI-related abdominal pain (43%) and neurotoxicity (12%). The intent-to-treat objective response rate was 42%, and 45% had stable disease, allowing complete CRLM resection/ablation in 27% of patients. After a median follow-up of 72 months, median overall and progression-free survival was 20 and 9 months, respectively. CONCLUSION: Addition of targeted therapy to systemic chemotherapy combined with HAI-oxaliplatin is feasible, safe and shows promising activity, even after systemic chemotherapy failure.
BACKGROUND: Hepatic arterial infusion (HAI) combined with systemic chemotherapy has shown promising results in patients with unresectable colorectal liver metastases (CRLM), even after failure to systemic therapy. Addition of systemic targeted therapies has been investigated with controversial results regarding tolerance, especially with HAI-floruxidine when combined with systemic bevacizumab. Our study aimed to analyse feasibility, safety and efficacy of HAI-oxaliplatin plus systemic chemotherapy and targeted therapies. METHODS: Between 2005 and 2016, single-centre consecutive patients with unresectable CRLM who received at least one cycle of HAI-oxaliplatin plus systemic chemotherapy and targeted therapies (cetuximab/panitumumab or bevacizumab) were analysed. RESULTS: A total of 89 patients (median age 55 years (range, 26-76 years) who previously received a median number of one systemic chemotherapy regimen (range, 0-5) including oxaliplatin in 78% of cases were included. Median number of HAI-oxaliplatin cycles was 9 (range, 1-28) combined with systemic chemotherapy and targeted therapies (LV5FU2 [63%], FOLFIRI [36%]) plus anti-EGFR (30%), or bevacizumab (70%). Grade 3/4 toxicities included neutropenia (40%), HAI-related abdominal pain (43%) and neurotoxicity (12%). The intent-to-treat objective response rate was 42%, and 45% had stable disease, allowing complete CRLM resection/ablation in 27% of patients. After a median follow-up of 72 months, median overall and progression-free survival was 20 and 9 months, respectively. CONCLUSION: Addition of targeted therapy to systemic chemotherapy combined with HAI-oxaliplatin is feasible, safe and shows promising activity, even after systemic chemotherapy failure.