Managing ADC-Associated Diarrhea: From Cholinergic Reactions to Delayed-Onset GI Toxicity

This segment focuses on diarrhea management with antibody-drug conjugates (ADCs) across breast and lung cancer, particularly sacituzumab govitecan (SG) and its irinotecan-like toxicity profile due to the SN-38 payload.

A discussion of diarrhea subtypes distinguishes early cholinergic diarrhea from delayed-onset diarrhea. NP Liz Castronovo describes using atropine as a pre-medication for cholinergic symptoms, drawing from experience with irinotecan in lung cancer. NP Stephanie McDonald notes that early cholinergic diarrhea presents with rapid-onset stomach cramping, sweating, and salivation—she adds atropine during infusion if symptoms occur, then pre-medicates for subsequent cycles. Dr. Rugo notes she has never observed cholinergic diarrhea with SG in breast cancer, suggesting possible differences related to dosing or scheduling.

Key considerations for delayed diarrhea management include loperamide after two loose stools, escalating to diphenoxylate-atropine if needed, and in rare cases tincture of opium. The panel emphasizes hydration monitoring, electrolyte assessment, and dietary modifications. Castronovo recommends stool diaries to identify triggers such as dairy or high-fat foods. Dr. Rugo discusses UGT1A1 polymorphism testing, noting that homozygous poor metabolizers experience more diarrhea and neutropenia; while not required by label, testing can guide dose reduction decisions. She describes octreotide as effective for refractory cases, having used it successfully in one patient to maintain therapy.