A Case of Multiple Intratumoral Hemorrhage and Rupture of Hepatocellular Carcinoma after Starting Lenvatinib

Abstract

A man in his 80s was administered lenvatinib to treat multiple hepatocellular carcinomas. After starting lenvatinib, he was admitted to our hospital for fever and epigastric tenderness. Conjunctival icterus and conjunctival pallor were observed. Computed tomography showed high density areas in his tumors which were suggestive of intratumoral hemorrhage and tumor rupture. As a result, the patient underwent an emergent angiography and arterial embolization.

Lenvatinib‐associated hemoperitoneum in a patient with primary angiosarcoma of the breast

“…Other hypothesized mechanisms of hemorrhage include the increased expression of collagenase, proliferation of elastin, and breakdown of collagen fibrils in small arteries of the carcinomas, resulting in stiff and brittle vessels that rupture easily. 3,9 Another possible reason for hemorrhage is the invasion and occlusion of the hepatic vein, resulting in intra-tumoral hemorrhage. 3,9 Lenvatinib is a multi-tyrosine kinase inhibitor developed as targeted therapy against the vascular endothelial growth factor receptor (VEGFR 1-3), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptor (PDGFR) and stem cell factor receptor (KIT).…”

“…2 Inhibiting angiogenesis in cancerous cells causes the remaining poorly developed tumor micro-vessels to collapse easily. 3 As VEGF F I G U R E 1 CT of the abdomen and pelvis with IV contrast: A large heterogeneously enhancing mass (black arrow) is centered in the caudate lobe, measuring approximately 5.5 cm. This mass appears to have ruptured with associated hemoperitoneum.…”

“…3,9 Another possible reason for hemorrhage is the invasion and occlusion of the hepatic vein, resulting in intra-tumoral hemorrhage. 3,9 Lenvatinib is a multi-tyrosine kinase inhibitor developed as targeted therapy against the vascular endothelial growth factor receptor (VEGFR 1-3), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptor (PDGFR) and stem cell factor receptor (KIT). These receptors play an essential role in tumor angiogenesis and the proliferation of cancer cells.…”

“…2 In addition to these, lenvatinib is associated with the occurrence of hemorrhagic events, including cerebral hemorrhage, intra-tumoral hemorrhage, and rupture of hepatocellular cancers. 3 In this report, we discuss a 32-year-old female with primary angiosarcoma of the breast with metastases to the liver complicated by hemoperitoneum while on lenvatinib.…”

Two Cases of Intraabdominal Bleeding Caused by Hepatocellular Carcinoma Rupture Soon after the Initiation of Chemotherapy with Lenvatinib

“…In contrast, in the REFLECT trial, cerebral hemorrhaging occurred in 3 of 462 patients (0.6%) during lenvatinib administration, despite the absence of HCC rupture in these patients ( 2 ). In clinical practice, following the approval of lenvatinib in Japan, Ishihara et al reported a patient with HCC who developed intratumoral hemorrhaging at 12 days after the initiation of lenvatinib ( 18 ). In the presently reported study, however, intraabdominal hemorrhaging caused by HCC rupture occurred earlier after the initiation of lenvatinib: Case 1 developed hemorrhaging at 3 days after lenvatinib initiation, and Case 2 developed hemorrhaging at 5 days after lenvatinib initiation.…”