What to do if imatinib (Gleevec) causes impaired renal function in patients with Gastrointestinal Stromal Tumor (GIST)?

Management of Imatinib-Induced Increased Creatinine in GIST Patients

For patients with GIST who develop increased creatinine while on imatinib therapy, continue treatment with appropriate monitoring and supportive care, as the benefits of continued therapy typically outweigh the risks of renal dysfunction. 1

Assessment of Renal Dysfunction

• Evaluate baseline renal function before initiating imatinib therapy, as a decline in estimated glomerular filtration rate (eGFR) is a known effect of imatinib treatment 1
• Monitor renal function regularly during therapy, with particular attention to risk factors for renal dysfunction including preexisting renal impairment, diabetes mellitus, hypertension, and congestive heart failure 1
• Assess for potential drug interactions that may exacerbate renal dysfunction 1

Management Algorithm

For Mild to Moderate Renal Dysfunction (CrCL 20-59 mL/min):

• Continue imatinib therapy at the current dose as studies show doses up to 800 mg daily for mild dysfunction and 600 mg daily for moderate dysfunction are generally well-tolerated 2
• Increase monitoring frequency of renal function tests 1
• Consider dose adjustment only if patient experiences other significant adverse events 2

For Severe Renal Dysfunction (CrCL <20 mL/min):

• Individualize dosing based on patient tolerance and disease response 2
• Consider referral to a nephrologist for co-management 3
• Monitor for serious adverse events, which are more common in patients with renal dysfunction 2

For Patients on Dialysis:

• Regular-dose imatinib (400 mg/day) can be maintained with appropriate monitoring, as case reports suggest it is generally well-tolerated in dialysis patients 4
• No dose adjustment is typically required as only 3-5% of imatinib is excreted through urine 2

Important Considerations

• Discontinuing imatinib therapy is generally not recommended as treatment interruption is associated with rapid disease progression in most cases 3
• Clinical experience suggests that discontinuing tyrosine kinase inhibitor therapy, even with progressive disease, may accelerate disease progression and worsen symptoms 3
• If severe renal toxicity occurs, temporary dose reduction or brief treatment interruption may be considered, with rechallenge at a lower dose after renal function improves 1

Alternative Treatment Options

• If renal dysfunction becomes severe and persistent despite dose adjustments:
  • Consider increasing imatinib dose to 800 mg daily if the patient was on a lower dose and has disease progression 3
  • Consider switching to sunitinib as second-line therapy if renal toxicity is intolerable 3
  • For patients who have progressed on both imatinib and sunitinib, regorafenib is recommended as third-line therapy 3

Monitoring Recommendations

• Regular assessment of renal function (serum creatinine, eGFR) 1
• Evaluation of tumor response with CT or MRI to ensure continued benefit of therapy 3
• Plasma level monitoring of imatinib may be useful in cases of unexpected toxicity or inadequate response 3
• Consider referral to a sarcoma specialty center for complex cases 3

Remember that the long-term benefits of continued imatinib therapy in controlling GIST typically outweigh the risks of mild to moderate renal dysfunction, and treatment should be maintained whenever possible with appropriate monitoring and supportive care 3, 5.