Copyright ©The Author(s) 2018.
World J Gastroenterol. Dec 14, 2018; 24(46): 5189-5202
Published online Dec 14, 2018. doi: 10.3748/wjg.v24.i46.5189
Table 1 The grade for the quality of evidence by the Grades of Recommendation Assessment, Development and Evaluation system
Final grade rankDefinition of grade rank
HighWe are very confident that the effect of the study reflects the actual effect
ModerateWe are quite confident that the effect in the study is close to the true effect, but it is also possible that it is substantially different
LowThe true effect may differ significantly from the estimate
Very lowThe true effect is likely to be substantially different from the estimated effect
Table 2 Summary of tyrosine kinase inhibitor-associated side effects
Side effectsRelative TKIsSymptomsMechanismsGeneral managementTKIs - dose reduction or temporary discontinuation
Edema and fluid retentionImatinibFrequently in the periorbital area or lower limbsInhibiting PDGFR and decreasing the interstitial pressureLimit salt intake or administer diureticsOccasionally
Gastrointestinal adverse eventsImatinib, sunitinib, regorafenibNause, vomiting, and diarrheaInducing release of neurotransmitters, exciting the vagus nerves and sympathetic nervesAntiemetic medications, Antidiarrhoeal medicineSeldom
Skin rashImatinib, sunitinibErythematous and maculopapular lesionsInhibiting of metabolic pathways mediated by tyrosine kinasesTopical lotions, antihistamines and steroidsSometimes
Ophthalmological complicationsImatinibPeriorbital edema, epiphora, and hemorrhage in the conjunctivaInhibiting PDGFR and decreasing the interstitial pressure, conjunctival chemosisSteroids and systemic diureticsNot necessary
HypertensionSunitinib, regorafenibHypertensionActivating the endothelin axis and suppressing reninACEIs, ARAsSometimes
Hand-foot syndromeSunitinib, regorafenibBilateral palmar plantar erythema, skin peeling, and painDirect skin toxicity of TKIs, poor repair of small traumas due to VEGFR and PDGFR inhibitionTopical creams, keratolytic creams, emollients, analgesicsOften
FatigueImatinib, sunitinib, regorafenibFatigue5-HT3 neurotransmitter disorder, proinflammatory cytokine accumulation, neuromuscular function degradationExercise intervention, nutritional supportSeldom
ProteinuriaSunitinib, regorafenib24 h urinary protein increaseVEGF inhibitionACEIs, ARAsSometimes
StomatitisSunitinib, regorafenibPain, edema, erythema, ulcers, burning sensationBlockade of the VEGFR signaling pathwayOral care, analgesicsSometimes
CardiotoxicitySunitinib, regorafenibQ-T interval prolongation, decreased LVEF, etcAMPK and PDGFR inhibitionACEIs, diureticsOften
HypothyroidismSunitinibClinical or subclinical hypothyroidismDestruction of the thyroid gland, inhibiting thyroid peroxidase activity, decreasing the density of thyroid capillariesSodium levothyroxineDon’t need
Hepatotoxicity and nephrotoxicityImatinib, sunitinib, regorafenibLiver transaminase elevation, creatinine elevationHBV reactivation, VEGF inhibitionAntiviral treatment, diammonium glycyrrhizinateSometimes
Hair disorderImatinibDiscoloration, trichomegaly, hypertrichosis, alopecia, etc.Inhibition of kit pathwayNoDon’t need
Interstitial lung diseaseImatinibfever of unknown origin, cough, dyspnea, hypoxemiaHypersensitivity reaction, inhibition of PDGFRSufficient corticosteroids, antibioticsDiscontiuation permanently in most cases
Hematological side effectsImatinib, sunitinib, regorafenibAnemia, neutropenia, thrombocytopeniaInhibiting KIT-expressing hematologic stem cellsFerrous sulfate, folate, G-CSF, TPOSometimes

  • Citation: Li J, Wang M, Zhang B, Wu X, Lin TL, Liu XF, Zhou Y, Zhang XH, Xu H, Shen LJ, Zou J, Lu P, Zhang D, Gu WJ, Zhang MX, Pan J, Cao H, Chinese Society of Surgeons for Gastrointestinal Stromal Tumor of the Chinese Medical Doctor Association. Chinese consensus on management of tyrosine kinase inhibitor-associated side effects in gastrointestinal stromal tumors. World J Gastroenterol 2018; 24(46): 5189-5202
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