Improved Control of Tyrosine Kinase Inhibitor-Induced Diarrhea with a Novel Chloride Channel Modulator: A Case Report

Area of Science:

• Oncology
• Gastroenterology
• Pharmacology

Background:

• Tyrosine kinase inhibitors (TKIs) are effective cancer therapies but often cause treatment-related diarrhea.
• Diarrhea can lead to dose reductions or treatment discontinuation, impacting patient outcomes.
• Metastatic papillary renal cell carcinoma (RCC) is a challenging diagnosis requiring effective systemic therapy.

Purpose of the Study:

• To present a case of managing severe, refractory diarrhea induced by tyrosine kinase inhibitors (TKIs) in a patient with metastatic renal cell carcinoma.
• To evaluate the efficacy of off-label crofelemer administration for TKI-induced diarrhea.
• To explore strategies for maintaining TKI therapy despite significant gastrointestinal side effects.

Main Methods:

• A 72-year-old patient with metastatic papillary RCC, recurrent after nephrectomy, was treated with multiple TKIs.
• The patient experienced severe, refractory diarrhea during cabozantinib therapy, necessitating dose adjustments.
• Off-label crofelemer was administered to manage the treatment-related diarrhea.

Main Results:

• Cabozantinib treatment led to a clinical response with nodal metastatic disease shrinkage.
• Severe diarrhea refractory to conventional management required dose holds and reductions of cabozantinib.
• Crofelemer administration successfully controlled the diarrhea, enabling cabozantinib dose escalation and continuation.

Conclusions:

• Crofelemer represents a potential therapeutic option for managing severe TKI-induced diarrhea.
• Effective management of treatment-related diarrhea can facilitate sustained TKI therapy and improve patient outcomes.
• This case highlights the importance of addressing side effects to optimize cancer treatment efficacy.