Catequentinib/rivoceranib

Abstract

Drug resistance and various toxicities: case report An approximately 24year-old man developed resistance while treatment with catequentinib for giant delayed pulmonary metastasis of osteosarcoma. He additionally developed fatigue, hypertension, diarrhoea, hand-foot skin syndrome, abnormal serum apoliporotein A, decreased thyroxine and elevated thyroid stimulating hormone during treatment with catequentinib and developed abdominal pain and fatigue during treatment with rivoceranib for giant delayed pulmonary metastasis of osteosarcoma [routes and durations of treatments to reactions onsets not stated; not all outcomes stated]. The man was admitted to the hospital on 5 April 2012 (at the age of 18 years) with complaints of local distending pain without apparent trigger of right knee, rubefaction, warm, swelling and oedema. The laboratory findings revealed exogenous neoplasm of right distal femur with irregular bone destruction and periosteal reaction. Based on the clinical presentation and laboratory findings, a diagnosis of common osteosarcoma was made. Therefore, he started receiving neoadjuvant chemotherapy (NAC) with doxorubicin, cisplatin, methotrexate, ifosfamide and folinic acid [calcium folinate]. However, his disease progressed. Therefore, NAC was stopped, and he underwent complete tumour resection. Post-operative chemotherapy was performed with 9 cycles of ifosfamide. Ten months after the initial surgery, an intramuscular mass with the size of 1.5 x 2cm2 beneath the surgical incision was noted. The mass was resected completely and the post-operative pathological diagnosis was osteosarcoma. Two months later (approximately at the age of 19 years), he had a second local recurrence later and received R0 resection. Thereafter, he was recruited in a randomised clinical trial and received treatment with docetaxel combined with lobaplatin for 5 cycles. After a symptom-free interval of 5 years (approximately at the age of 24 years), he was readmitted to the hospital due to increasing cough and dyspnoea for duration of 2 months. The laboratory findings showed a giant neoplasm in the pulmo dexter crossing the upper and lower lobe with a small pleural effusion. Based on the clinical presentation and laboratory findings, giant delayed pulmonary metastasis of osteosarcoma was highly considered. Due to his refusal to receive chemotherapy, and his poor physical condition, which was intolerable for invasive surgery, he started receiving treatment with catequentinib [anlotinib] 12mg once daily on a 2 week on and one week off. After 6 weeks of catequentinib therapy, stable disease with 30% shrinkage of volume was noted. The lesion shrank persistently and more than 82% reduction was considered as partial response after 24 weeks of treatment as compared to the initial volume before catequentinib treatment. After 27 weeks of catequentinib therapy, the tumour volume unfortunately increased 80% compared to 24 weeks, indicating progressive disease. As a result, resistance to catequentinib was considered. The man’s therapy with catequentinib was stopped. Thereafter, the argon-helium cryoablation (AHC), American superconductor argon-helium surgical system equipped with 5mm freezing probes was recommended to reduce the tumour burden. Subsequently, the eastern cooperative oncology group performance status (ECOG PS) deteriorated from 2 to 4, and he unable to walk or work due to progressive chest pain and panting. Thereafter, he started receiving rivoceranib [apatinib] 500mg daily. As a result, his disease stablilised for 4 weeks; however, no improvement was noted in ECOG PS. He developed catequentinib-related toxicities including grade 2 fatigue, grade 2 hypertension, grade 1 diarrhoea, grade 1 hand-foot skin syndrome, grade 1 abnormal serum apoliporotein A, grade 1 decreased thyroxine and grade 1 elevated thyroid stimulating hormone. These toxicities were controllable and well tolerated. He additionally developed rivoceranib-related toxicities including grade 1 abdominal pain and grade 1 fatigue. After 8 weeks of rivoceranib administration, he died due to increasing dyspnoea.