Antineoplastics

Abstract

Febrile neutropenia and acute liver failure secondary to drug toxicity: 2 case reports In a case series, two siblings were described of whom, a 6-year-old girl developed febrile neutropenia during treatment with doxorubicin, vincristine, methotrexate and cisplatin for osteosarcoma of the distal right femur and a 5-year-old boy developed acute liver failure secondary to methotrexate toxicity during treatment with methotrexate for osteoblastic osteosarcoma of the proximal tibia [not all routes and dosages stated; duration of treatment to reaction onset not stated]. Case 1: The girl was diagnosed with osteosarcoma of the distal right femur. She was initiated on neo-adjuvant chemotherapy consisting of two cycles of IV methotrexate 12 g/m2, cisplatin 120 mg/m2 and doxorubicin [Adriamycin] 75 mg/m2. Later on, she was referred to a centre in Spain, and her therapy was switched to intra-arterial cisplatin 150 mg/m2, IV doxorubicin 100 mg/m2 and one dose of vincristine 1mg. After neoadjuvant therapy, she underwent limb-sparing surgery, in which tumour resection with distal femur reconstruction with an osteoarticular allograft, was performed. The pathology of the resected tumor was indicative of osteoblastic osteosarcoma of the distal femur with 95% tumor necrosis. She did not receive adjuvant chemotherapy due to a high degree of haematological toxicity manifested in the form of grade 4 febrile neutropenia, which was attributed to the neo-adjuvant therapy with methotrexate, doxorubicin and cisplatin and additional cycles of neo-adjuvant chemotherapy with cisplatin, doxorubicin and vincristine. The occurrence of osteosarcoma was attributed to the Rothmund-Thomson syndrome (RTS), which was diagnosed through germline genetic analysis. Case 2: The boy was diagnosed with osteoblastic osteosarcoma of the proximal tibia. He was initiated on neoadjuvant chemotherapy with cisplatin and doxorubicin. The tumour was resected and the pathology of resected piece showed 100% necrotic osteoblastic osteosarcoma. Adjuvant chemotherapy was initiated with high dose methotrexate, cisplatin and doxorubicin. However, he developed acute liver failure secondary to methotrexate toxicity, which manifested in the form of hypertransaminasemia, hyperbilirubinemia and coagulopathy. He received cholestyramine and activated charcoal for the treatment of acute liver failure. His chemotherapy regimen was switched to cisplatin and doxorubicin. He was in remission from February 2020 to August 2020. The occurrence of osteosarcoma was attributed to the Rothmund-Thomson syndrome (RTS), which was diagnosed through germline genetic analysis.