Defibrotide/oxaliplatinSinusoidal obstruction syndrome and lack of efficacy following off label use: case report A 43-year-old man developed sinusoidal obstruction syndrome (SOS) during treatment with oxaliplatin for metastatic left colon adenocarcinoma. Subsequently, he exhibited lack of efficacy during off label treatment with defibrotide for oxaliplatin-induced SOS [not all routes stated].The man was diagnosed with left colon adenocarcinoma, with synchronous bi-lobar liver metastases. As metastatic lesions were unresectable, he received first-line FOLFIRI regimen comprising folinic acid, fluorouracil and irinotecan along with cetuximab from December 2017 to April 2018. In May 2018, to prevent further complications and to explore the peritoneal cavity, he underwent a resection of the primary tumour. Inspite of partial response to first-line chemotherapy, metastases were still considered unresectable. Therefore, treatment was intensified. Therefore, after percutaneous implantation of hepatic arterial infusion (HAI) catheter, he received irinotecan and oxaliplatin 85 mg/m 2 via HAI in combination with intravenous folinic acid [leucovorin] and fluorouracil [5-fluorouracil] combined with panitumumab. From September 2018 to April 2020, he received 28 cycles of oxaliplatinbased HAI (cumulative oxaliplatin dose of 4585 mg). Liver metastases remained stable under this regimen. However minor progressions were observed, when cycles were spaced out every 3 or 4 weeks instead of 2. In June 2020, he developed jaundice. Initial analyses revealed normal leukocytes and haemoglobin levels, mild thrombocytopenia, normal renal function, international normalization ratio of 1.1, total bilirubin of 98 µmol/L (conjugated 85 µmol/L), albumin of 35 g/L, ALT was 3 times upper limit of normal (ULN), gamma glutamyl transpeptidase was 14 times ULN, AST was 2 times ULN and alkaline phosphatase was 7 times ULN. Thereafter, a CT-scan revealed no progression of metastases, no portal thrombi and no bile duct dilatation; however, splenomegaly was observed. A biopsy was performed under ultrasound scan guidance in extra-tumoural liver and showed SOS with nodular regenerative hyperplasia, necrosis of the biliary epithelium with intralobular cholestasis (cholestatic thrombi within the biliary microduct), perisinusoidal fibrosis with residual centro-lobular veins (some were with luminal thrombi) and altered hepatic architecture with nodular features without fibrosis of the hepatocyte framework. Therefore, he was diagnosed with SOS, which was attributed to oxaliplatin.Thereafter, the man was treated with off label defibrotide 25 mg/kg/day (575mg every 6 hours for 21 days. However, this treatment did not improve his liver function (lack of efficacy). Eventually, he died of liver failure at the end of August 2020, 5 weeks after the end of treatment.
