Targeted drugs for advanced gastric cancer in China are currently represented by trastuzumab (Trastuzumab, trade name Herceptin) and apatinib. In the process of applying targeted therapy, there are some precautions that patients need to know.
Pre-treatment comprehensive evaluation
Before treatment, the physician will perform a thorough evaluation of the patient, including medical history, physical status, tumor status, and, in patients considering trastuzumab, cardiac function. Therefore, patients usually undergo routine blood tests, blood biochemistry, tumor markers, CT, etc. For cardiac evaluation, ECG, echocardiography, or radiographic cardiovascular imaging may be used.
Regular follow-up during treatment
Before each cycle of medication, the physician usually performs a physical exam to review ECG, routine blood tests, and blood biochemistry. During targeted therapy, patients also need to receive regular checkups. Weekly follow-up of routine blood tests and blood biochemistry is recommended to closely monitor drug-related adverse events and provide timely symptomatic management.
Considering the cardiotoxicity of trastuzumab, patients should usually undergo an echocardiogram or radiographic cardiography every 3 months to assess cardiac function. Given the effects of apatinib on blood pressure and the kidneys, patients also have their blood pressure measured and urine checked regularly while on the drug, and patients with renal insufficiency have their kidney function and proteinuria checked regularly.
During treatment, the doctor may consider suspending the drug if serious adverse reactions or disease progression are detected. The length of time to discontinue the drug and the dose to restart the drug are dependent on the situation. If the drug is discontinued for longer than a certain period of time, it may be necessary to discontinue the targeted therapy.
Prevention and management of adverse reactions
Trastuzumab
- Cardiac toxicity. The risk of cardiotoxicity is higher in the following groups: advanced age, previous history of cardiac disease, previous application of anthracyclines, previous combination of trastuzumab and anthracyclines. Cardiotoxicity may manifest itself as tachycardia, palpitations (spontaneous heartbeat or panic), dyspnea, and chest pain, or may be detected as a decrease in left ventricular ejection fraction (LVEF) without associated symptoms, and patients may develop congestive heart failure. Doctors typically ask patients to monitor LVEF regularly and use medications such as angiotensin-converting enzyme inhibitors as appropriate.
- Infusion Reaction. About 40% of patients will have an infusion reaction to the first trastuzumab infusion, most commonly chills and fever, and may be treated with acetaminophen (Paracetamol), Diphenhydramine, or Pethidine (Dulcolax), potentially slowing the rate of trastuzumab infusion.
Manifestations of infusion reactions also include nausea, vomiting, pain at the tumor site, headache, dizziness, dyspnea, hypotension, elevated blood pressure, rash, and malaise. In mild to moderate infusion reactions, the physician will usually slow the infusion rate; in patients with dyspnea or significant hypotension, the infusion will usually be interrupted; and in severe and life-threatening infusion reactions, the trastuzumab infusion will usually be stopped permanently.
- Pulmonary toxicity. Less common, with an incidence of only 0. 4% to 0. 6%. Doctors will generally consider discontinuing therapy if there are signs of pulmonary toxicity such as pneumonia and respiratory failure. In people with previous lung disease or extensive lung metastases, or respiratory distress in the quiet state, doctors usually evaluate the benefits and risks of trastuzumab treatment and choose it carefully, as well as closely monitor the patient’s condition during treatment and emphasize timely follow-up.
Apatinib
While most adverse reactions to apatinib can be managed and reversed with dose suspension, dose downward adjustment, and supportive symptomatic management, there are still some adverse reactions that require special attention.
- Hypertension. Hypertension is one of the most common adverse reactions to apatinib, with an incidence of 36. 32%, including 5. 38% for grade 3 hypertension (blood pressure not less than 180/110 mmHg). Blood pressure is usually measured before starting the drug and should be monitored throughout treatment, especially daily for the first 2 weeks of treatment. Patients with hypertension usually require antihypertensive medication to control blood pressure to <140/90 mm Hg before apatinib is administered, but patients with normal blood pressure do not require prophylactic blood pressure lowering. During treatment, patients should contact their physician immediately if their blood pressure does not fall below 140/90 mmHg or if they develop symptoms associated with elevated blood pressure such as significant headache, dizziness, or visual disturbances.
- Proteinuria. In clinical studies, the incidence of proteinuria with apatinib was 44. 36%, with grade 3 proteinuria occurring at a rate of 1.79%. Proteinuria typically occurs about 3 weeks after dosing and is usually asymptomatic and reversible, and can be relieved by suspension of dosing or downward dose adjustment without special management. Patients with renal insufficiency need to be closely monitored while taking apatinib. Regular urine tests, blood pressure, renal function and proteinuria are usually required, usually every 2 weeks for the first 2 months and every 4 weeks thereafter, and proteinuria should be seen promptly.
- Hand-foot skin reaction (HFSR). In clinical studies, the incidence of HFSR was 27. 35%, with a grade 3 HFSR incidence of 7. 62%. Apatinib-induced HFSR occurred mostly 2 to 3 weeks after dosing. During treatment, injury and friction to the palms and soles of the feet should be avoided, for example, by wearing loose, breathable shoes, soft cotton gloves and threaded socks, using gel insoles, and avoiding strenuous exercise. Both hands and feet should avoid exposure to high heat and direct sunlight, and use skin care products that are moisturizing and contain lanolin or urea ingredients. Avoid spicy, irritating foods. If more severe HFSR occurs, promptly inform your doctor, who will take the necessary symptomatic treatment measures.
- Bleeding. Although studies have not found a significant increase in bleeding tendency with apatinib, one should be alert to the possible risk of bleeding given its mechanism of action and the experience with other similar agents. Apatinib should be used with caution in patients receiving thrombolytic or anticoagulant therapy and in patients at high risk of bleeding (e.g., gastric ulcer with positive fecal occult blood, recent history of vomiting blood or dark stools, abnormal coagulation with bleeding tendency). During dosing, attention should be paid to any bleeding-related symptoms and immediate medical attention should be sought if abnormalities are detected.
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In conclusion, the doctor will conduct a thorough evaluation before applying targeted drugs, and patients should pay attention to the symptoms during the treatment process, regularly visit the doctor for review, and seek medical attention when abnormalities are detected to safely use targeted drugs as a powerful tool against cancer. (Contributed by Yanwen Diao, Department of Medical Oncology, The First Affiliated Hospital of China Medical University)