Gastrointestinal Toxicities of Targeted Cancer Therapies: A Narrative Review.

Targeted cancer therapies have transformed the management of solid and hematologic malignancies through pathway-specific disease control across diverse tumor types. Despite these advances, gastrointestinal toxicities remain among the most frequent and clinically consequential adverse effects associated with these agents, often leading to dose interruptions, treatment discontinuation, and reduced adherence. Diarrhea is the dose-limiting and most prevalent gastrointestinal adverse event among various classes of targeted therapies, and nausea, vomiting, oral mucositis, and less frequent high-impact events cause varying degrees of patient-related morbidity. To address practical outpatient decision-making gaps, this narrative review synthesizes peer-reviewed literature identified primarily through PubMed/MEDLINE and supplemented by manual screening of reference lists from key guidelines, clinical trials, and expert reviews. This review proposes a pharmacology-informed Mechanism-Exposure-Severity-Escalation (MESE) framework to organize gastrointestinal toxicity assessment and management by linking drug class mechanisms and exposure-modifying factors to severity-based intervention and escalation thresholds. Evidence was based on clinical practice guidelines, pivotal randomized trials, supportive care intervention studies, quality of evidence on pharmacokinetic and drug-drug interaction studies, and on observational safety reports with a focus on pharmacist-relevant decisions in routine practice. Across the literature, targeted therapy-associated diarrhea emerged as a mechanistically heterogeneous toxicity with substantial variability in incidence, severity, and management requirements across drug classes. Evidence supports early, structured antidiarrheal intervention, selected prophylactic strategies for predictable high-risk agents, and proactive identification of pharmacokinetic modifiers, including gastric acid suppression, that may influence drug exposure and clinical outcomes. Other gastrointestinal toxicities, including oral mucositis, nausea, vomiting, and rare high-impact complications, are integrated within the framework through guideline-directed supportive care, class-specific prevention strategies, and defined escalation pathways when clinically indicated. Collectively, these findings support a pharmacist-forward, pharmacology-informed approach to outpatient gastrointestinal toxicity management that integrates mechanism-aware assessment, exposure-risk evaluation, and clearly defined escalation thresholds to preserve treatment continuity while safeguarding patient safety.