From:  Multikinase and highly selective kinase inhibitors in the neoadjuvant treatment of patients with thyroid cancer

Management of the main AEs experienced by the patients during MKIs and HS-TKIs treatment

AEManagement of AEs
Hypertension1. ACEI, ARBs, diuretics, beta-blockers, alpha-blockers, nitrate derivates, calcium channel blockers (low interaction potential)
2. Nifedipine (use cautiously)
DiarrheaGrade 1: oral hydration and electrolyte replacement; initiate anti-diarrheal medication (loperamide; opioids: diphenoxylate/atropine, tincture of opium); BRAT diet
Grade 2: intravenous (IV) fluids if the patient is unable to tolerate oral fluids; initiate/continue anti-diarrheal as mentioned above; BRAT diet; anticholinergic agents (hyoscyamine, atropine)
Persistent grades 2, 3, 4: patient hospitalization (intensive care for grade 4); provide IV fluids and use anti-diarrheal agents and anticholinergics as mentioned above; consider octreotide
Skin rashSkin protection; urea lotion
Weight loss, anorexia, nauseaGrade 1–2: generally, do not warrant interruption of drug unless intolerable AE despite optimal management
Grade 3 or intolerable adverse reactions: require interruption of the drug until resolution or improvement of AE and restart the drug at a reduced dose
Grade 4: discontinue treatment in case of life-threatening reactions
Intervention:
1. Nutritional supplements
2. Appetite stimulation drugs: megestrol acetate, medroxyprogesterone acetate, dexamethasone, cannabinoids
3. Antinausea drugs: metoclopramide
4. Nutrionist counseling
Fatigue1. Screening and earlier symptoms management
2. Rate the patient level of fatigue on a scale of 0 to 10 (i.e., visual analogue scale, FACT-F)
3. Encouraged patient to maintain an active lifestyle
4. Agopunture
5. Taking MKI in the evening (rather than during the day) can minimize daytime fatigue
6. Exclude the comorbidities (anemia, hypothyroidism, hypogonadism, etc.) or electrolyte abnormalities
In case of severe fatigue:
1. Psychosocial intervention and exercise
2. Management of sleep disturbances
3. Pharmacological intervention (central nervous system stimulants, antidepressant)
QTc prolongationGrade 1 (450–480 ms): no drug interruption but careful follow-up
Grade 2 (481–500 ms) and grade ≥ 3 (> 501 ms or > 60 ms compared to baseline): discontinue treatment
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MKIs: multikinase inhibitors; HS-TKIs: highly selective tyrosine kinase inhibitors; ACEI: angiotensin-converting enzyme inhibitors; ARBs: angiotensin receptor blockers; BRAT diet: banana, rice, applesauce, toast; AE: adverse event; FACT-F: Functional Assessment of Cancer Therapy-Fatigue; QTc: QT interval corrected for heart rate