Cometriq

Cabozantinib therapy is associated with numerous toxic adverse effects.‍‍‍‍‍‍​​​‍​​​​​​ Most of these appear within the first eight weeks of treatment. Therefore, the physician should be able to determine after this period whether dose modification is required. Events occurring early in chemotherapy include: hypocalcaemia, hypokalaemia, thrombocytopenia, hypertension, palmar-plantar erythrodysaesthesia, proteinuria, and gastrointestinal disorders. Hepatic impairment frequently occurs in patients treated with cabozantinib, manifested by elevated hepatic transaminases (AST and ALT) and increased bilirubin levels. It is therefore essential to check these parameters before initiating chemotherapy and to monitor them carefully during treatment. Particular attention should be paid to patients with moderate hepatic impairment, as hepatic encephalopathy developed more frequently during cabozantinib therapy in this population. The use of this chemotherapeutic agent is not recommended in patients with severe hepatic impairment, as it has not been studied in this population. Cabozantinib use is associated with adverse effects such as diarrhoea, vomiting, decreased appetite, and electrolyte disturbances. In patients with HCC and compromised hepatic function, such non-hepatic drug effects may trigger the development of hepatic encephalopathy. Patients should be monitored for signs and symptoms of this condition. Serious gastrointestinal perforations and fistulae, sometimes fatal, have been observed in patients treated with cabozantinib. Patients with inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis, peritonitis, diverticulitis, or appendicitis), patients with tumour infiltration of the gastrointestinal tract, or patients with delayed or incomplete healing of the gastrointestinal tract following surgery should be carefully evaluated before initiating chemotherapy. They should subsequently be closely monitored for signs of perforation and fistulae, including abscesses and sepsis. Patients with persistent or recurrent diarrhoea during treatment may be at risk of developing anal fistula. Cabozantinib therapy must be discontinued in patients who develop gastrointestinal perforation or fistula that cannot be managed medically. Diarrhoea, vomiting, decreased appetite, and electrolyte disturbances are the most common adverse effects associated with cabozantinib therapy. As soon as they occur, supportive treatment with antiemetic, antidiarrhoeal, and rehydration agents should be promptly initiated. If toxic effects persist despite these measures, treatment interruption, dose reduction, or discontinuation of cabozantinib is required. Since thromboembolic events (venous, arterial, pulmonary) have occurred in patients treated with cabozantinib, caution should be exercised when using this drug in patients with risk factors for such events or with a relevant medical history. If acute myocardial infarction or other clinically significant thromboembolic complications occur, cabozantinib therapy must be discontinued. Cases of severe haemorrhage, including fatal outcomes, have been reported in patients treated with cabozantinib. Patients with a history of serious bleeding prior to initiating therapy should undergo thorough evaluation before cabozantinib is commenced. The drug is not recommended for use in patients with severe haemorrhage or an increased risk thereof. The use of VEGF pathway inhibitors is a predisposing factor for aneurysm formation and/or arterial dissection; therefore, this risk should be carefully considered before initiating cabozantinib, particularly in patients with predisposing factors such as hypertension or a history of aneurysm. Cabozantinib therapy carries a risk of excessive thrombocytopenia; therefore, platelet counts should be monitored during treatment. Wound healing has been observed to be frequently impaired in patients treated with cabozantinib. For this reason, the chemotherapeutic agent should be discontinued at least 28 days before planned surgical procedures (including dental surgery or invasive dental procedures). If wounds require medical intervention to heal, chemotherapy should be interrupted. It is essential to check blood pressure values in all patients before initiating cabozantinib therapy, as treatment may cause hypertension. In cases of persistent hypertension, antihypertensive agents should be administered. If hypertension persists despite treatment or if a hypertensive crisis occurs, therapy should be discontinued. Cases of osteonecrosis of the jaw have been observed during cabozantinib therapy; therefore, an oral examination should be performed before initiating treatment, regularly monitored during therapy, and patients should be advised about the importance of maintaining oral hygiene. Particular caution should be exercised in patients receiving concomitant bisphosphonates. Cabozantinib treatment must be interrupted if osteonecrosis of the jaw develops. Attention should be paid to the occurrence of palmar-plantar erythrodysaesthesia in patients treated with cabozantinib. If severe, treatment with the chemotherapeutic agent should be discontinued and resumed once symptoms have resolved to Grade 1. Due to the increased risk of proteinuria in patients treated with cabozantinib, urinary protein levels should be regularly monitored. In the event of nephrotic syndrome, a treatment interruption should be instituted. Cases of posterior reversible encephalopathy syndrome have been observed in patients treated with cabozantinib. In any patient presenting with multiple symptoms such as seizures, headache, visual disturbances, or confusion, the risk of this syndrome is real and should be considered. If posterior reversible encephalopathy syndrome develops, chemotherapy with this agent should be discontinued. Cabozantinib therapy must be administered with caution in patients with a history of QT prolongation, cardiac dysfunction, electrolyte disturbances, and circulatory disorders. In this population, ECG should be performed regularly and serum calcium, potassium, and magnesium levels should be monitored.