Due to fedratinib's significant GI side effect profile and the logistical difficulty of measuring thiamine levels, clinicians should proactively provide patients with thiamine supplements, anti-emetics, and anti-diarrheal therapies. Instructing patients to take the drug with food can also help mitigate GI toxicity.

The failure of an adjuvant trial for the TKI pazopanib was likely caused by a protocol change that reduced the dose to manage transaminitis. While well-intentioned to improve tolerability and adherence, the lower dose was sub-therapeutic. This serves as a critical lesson that managing side effects by compromising dose can nullify a drug's potential efficacy.

When combining sacituzumab govitecan (SASE) and pembrolizumab (IO), it's crucial to differentiate the cause of diarrhea. SASE-induced diarrhea is similar to standard chemotherapy, while IO-induced diarrhea often presents with bloody stools and severe abdominal cramping.

The HORIZON-GEA-01 trial for zanidatumab in gastric cancer mandated prophylactic loperamide (4mg BID) for all patients. This was necessary to manage the high rates of diarrhea (up to 80% of patients), a significant GI toxicity associated with the drug's mechanism of action.

Clinicians are finding that forgoing the standard 800mg loading dose of zolbituximab and starting directly with the 600mg maintenance dose appears to mitigate acute gastrointestinal toxicity, particularly gastritis. This practical adjustment is being formally studied but is already used in practice to improve patient experience.

The Phase 2 TRAIT study suggests starting adjuvant abemaciclib at a lower dose and escalating over several weeks significantly reduces early discontinuations due to side effects like diarrhea. This strategy helps more patients get through the initial high-toxicity period and remain on the effective dose for the full two-year course.

For patients sensitive to standard loperamide tablets who experience rebound constipation, the liquid formulation offers more flexible, precise dosing. This allows for better symptom control of diarrhea without overcorrecting and causing constipation, improving overall patient tolerance.

In a phase 2 trial, the combination of zanidatumab and FOLFOX achieved a remarkable 95% response rate after two key modifications were made: adding prophylactic loperamide and dropping the 5-FU bolus. This suggests the bolus adds toxicity without clear benefit in this specific, potent combination.

When patients experience a consistent pattern of diarrhea, clinicians should move from a reactive, per-episode dosing strategy to a proactive, scheduled regimen of loperamide. This provides better control and prevents symptoms from escalating, with the option to de-escalate as the patient stabilizes.