Imatinib Side Effects Chronic phase: recommended initial dose is 400 mg once daily. Accelerated and acute phase: recommended initial dose is 600 mg once daily, increasing to 800 mg if necessary Chronic phase Neutrophils (ANC) <1.0x10^9/L and/or platelets <50x10^9/L: Suspend imatinib until ANC is ≥1.5x109/L and platelets are ≥75x109/L, then continue imatinib at a starting dose of 400 mg. If neutrophils are again <1.0x10^9/L and/or platelets <50x10^9/L, discontinue until ≥1.5x10^9/L and platelets ≥75x109/L, then treat with 300 mg of imatinib. Accelerated and acute phase Neutrophils <0.5x10^9/L and/or platelets <10x10^9/L: Patients may have disease-related cytopenia. If cytopenia is not disease-related, reduce dose to 400 mg. If cytopenia persists for 2 weeks, further reduce dose to 300 mg. If cytopenia persists for 4 weeks, discontinue imatinib until ANC ≥1.0x109/L and platelet count ≥20x109/L, then resume therapy at a dose of 300 mg. Growth factors may be used in combination with imatinib in patients with persistent neutropenia. Anemia needs to be excluded as nutritional and transfused if necessary. Try not to use erythropoietin for fear of elevated thrombotic probability. Non-hematologic toxicity Bilirubin >3x IULN or hepatic transaminases >5x IULN (upper limit of normal): suspend imatinib until bilirubin is <1.5x IULN (upper limit of normal) and transaminase levels are <2.5x IULN. imatinib dose reduced to (400-300 mg, 600-400 mg, or 800-600 mg) daily. Severe hepatotoxicity or severe fluid retention: suspend imatinib until resolution of the event. Treatment may be resumed as appropriate depending on the severity of the event. Patients with moderate renal impairment (creatinine clearance [CrCl] = 20-39 mL/min) should receive 50% of recommended therapy, with starting and future doses increasing as tolerated. Dose impairment in excess of 600 mg is not recommended for patients with mild renal impairment (CrCl = 40-59 mL/min). Doses greater than 400 mg are not recommended for patients with moderate renal impairment. Imatinib should be used with caution in patients with severe renal impairment. Fluid retention (i.e., pleural effusion, pericardial effusion, edema, ascites): diuresis, dose reduction, interruption, or discontinuation. Consider echocardiography for left ventricular ejection fraction (LVEF). No need to change medication. Gastrointestinal upset: take medication with a meal and drink a large glass of water. Muscle cramps: take calcium and hydration. Rash: local or systemic steroid, dose reduction, dose interruption, or dose interruption. Side effects of nilotinib Newly diagnosed chronic phase: an initial dose of 300 mg twice daily is recommended. Chronic or accelerated phase of resistance or poor therapeutic efficacy: the recommended initial dose is 400 mg twice daily. Acute phase: the recommended initial dose is 400 mg twice daily. Nilotinib prolongs the QT interval. Prior to taking nilotinib, regularly monitor for hypokalemia or hypomagnesemia, as well as correct deficiencies. An electrocardiogram (ECG) must be measured before dosing, 7 days after treatment, and periodic monitoring. Sudden death has been reported in patients treated with nilotinib. Avoid combinations of drugs known to prolong the QT interval and strong CYP3A4 inhibitors. Patients should avoid eating 2 hours before and 1 hour after taking the drug. QT time prolongation QT interval >480 ms ECG: Suspend nilotinib. If serum potassium and magnesium levels are low or lower limit of normal, supplement to upper limit of normal. If QT interval returns to <450 ms and within 20 ms of baseline within 2 weeks, resume prior dose after. If, after 2 weeks, the QT interval is between 450 and 480 milliseconds, reduce the dose to (400 mg once daily). If, after dose reduction, the QT interval returns to >480 ms, nilotinib should be discontinued. Electrocardiograms should be performed to test the QT interval 7 days after any dose. Hematotoxicity Chronic or accelerated phase, ANC <1.0x10^9/L, and/or platelets <50x10^9/L: suspend nilotinib and monitor blood counts. If ANC >1.0×10^9/L and platelets >50×10^9/L at 2 weeks, continue prior dose; if blood counts remain low for more than 2 weeks, reduce dose to 400 mg once daily. Dasatinib treatment Chronic phase: recommended initial dose is 100 mg once daily. Accelerated and acute phase: the recommended initial dose is 140 mg once daily. Chronic phase ANC <0.5x10^9/L or platelets <50x10^9/L: Suspend dasatinib until ANC ≥1.0x10^9/L and platelets ≥50x10^9/L, then continue dasatinib. At starting dose, if recovery occurs in ≤ 7 days. If platelets <25x10^9/L or ANC recurrence <0.5x10^9/L persists for >7 days, discontinue dasatinib until ANC ≥1.0×10^9/L and platelets ≥50×10^9/L, then resume dasatinib at the second episode once daily at a dose reduction of 80 mg once daily. once daily (for patients with a new diagnosis) further reduce the dose to 50 mg, or Discontinuation of dasatinib (for patients who are resistant or refractory to prior therapy, including imatinib). Accelerated and acute phase, ANC <0.5x10^9 and/or platelets <10x109/L: Patients may have disease-related cytopenia. If the cytopenia is not disease-related, suspend dasatinib until ANC ≥1.0x10^9 and platelets ≥20x10^9 and return to initial dose. If decreased again, suspend dasatinib until ANC ≥1.0x10^9 and platelets ≥20x10^9 once daily and resume dasatinib at a reduced dose of 100 mg (second reduction) or 8 mg once daily (third reduction). Growth factors may be used in combination with dasatinib in patients with persistent neutropenia and thrombocytopenia. Non-Hematological Toxicity If a serious non-hematological adverse reaction occurs with dasatinib, treatment must be suspended until the event resolves or improves. Thereafter, depending on the initial severity of the event, treatment may be resumed at a reduced dose as appropriate. Pulmonary Arterial Hypertension (PAH): a rare but significant side effect. Dasatinib can cause PAH, which can occur at any time after onset, including more than one year of treatment. PAH may return after discontinuation of dasatinib. Evaluate patients for potential signs and symptoms, cardiopulmonary disease before and during initiation of dasatinib therapy. If PAH is recognized, dasatinib should never be reapplied. Specific Interventions Fluid retention events (i.e., ascites, edema, pleural and pericardial effusions): diuretics, nursing care. Pleural/pericardial effusion: diuretics, suspension of TKI. consider short-term administration of steroid (prednisone) 20-50 mg/day for 3-4 days if patient is significantly symptomatic, may be tapered to 20 mg/day for 3-4 days); dasatinib will need to be tapered after treatment resolves. Gastrointestinal upset: take medication with a meal and drink a large glass of water. Rash: local or systemic steroids, dose reduction, dose interruption, or dose interruption. Flumatinib is a 2-generation drug available in China, and in a study led by Prof. Jianxiang Wang, 394 patients in chronic phase were randomly assigned to receive flumatinib (600 mg once daily) versus imatinib (400 mg once daily) [1]. At 12 months, more patients received flumatinib (23% versus 12%) and no patients progressed compared to those receiving imatinib (versus four patients receiving imatinib). Adverse events such as edema, extremity pain, rash, neutropenia, anemia, and hypophosphatemia were more common in the imatinib arm, while diarrhea and elevated alanine aminotransferase were more common in the flumatinib arm. The shortcoming of this trial from large phase 3 studies of other 2G drugs is that only 7% of patients were at high risk.