Opinion
Video
Who, When, and How: Navigating Combination Therapies in mCRC
Panelists discuss how managing common toxicities in combination therapies requires specific strategies including dose reductions and growth factor support for neutropenia with trifluridine/tipiracil, antihypertensive management for blood pressure elevations across different agents, and careful patient selection considering contraindications such as previous pelvic radiation (GI perforation risk), cardiac conditions, anticoagulation therapy (hemorrhage risk), hepatic impairment, advanced age, and complex pill burden management, emphasizing the importance of multidisciplinary care and selecting conscientious patients capable of adhering to precise dosing requirements.
Effective toxicity management is crucial for optimizing patient outcomes with combination therapies in metastatic colorectal cancer. For neutropenia associated with trifluridine/tipiracil (FTD/TPI), management involves holding treatment and resuming with dose reductions of 5mg/m² when blood counts recover, often supplemented with growth factor support using filgrastim between days 6-7 or days 13-15 of the 28-day cycle. Hypertension management varies by agent: fruquintinib requires intervention for grade 3 hypertension (>160/100 mmHg) with antihypertensive initiation or adjustment, regorafenib requires management for symptomatic grade 2 hypertension (140-159/90-99 mmHg), while bevacizumab necessitates blood pressure control for any grade of hypertension, with drug discontinuation reserved for uncontrolled severe cases or hypertensive crisis.
Specific patient populations require heightened caution when considering combination therapy with trifluridine/tipiracil plus bevacizumab. Patients with previous pelvic radiation face increased gastrointestinal perforation risk, typically occurring within the first 50 days of bevacizumab initiation. Those with preexisting cardiac conditions including heart failure may experience reversible direct myocardial toxicity or exacerbation of underlying cardiac dysfunction. Patients on anticoagulation therapy have elevated hemorrhage risk ranging from minor epistaxis to severe complications including hemoptysis, gastrointestinal bleeding, or central nervous system hemorrhage. Additionally, individuals with existing hypertension may experience difficult-to-control blood pressure elevation, while those with thrombotic history require careful monitoring despite continued treatment eligibility.
Patient-specific considerations extend beyond traditional contraindications to include hepatic function and age-related factors. Patients with elevated bilirubin levels (1.5-3 times upper limit of normal) demonstrate increased risk of grade 3-4 bilirubin elevations in clinical practice, while elderly patients over 65 experience higher rates of severe hematologic toxicities including neutropenia, thrombocytopenia, and anemia. The complex pill burden associated with trifluridine/tipiracil, which comes in multiple strengths requiring careful dosing calculations and potential multiple bottles for dose reductions, necessitates selecting conscientious patients capable of adhering to precise dosing instructions. These considerations underscore the importance of multidisciplinary care coordination to customize treatment approaches based on individual patient profiles and comorbidities.
Newsletter
Stay informed on drug updates, treatment guidelines, and pharmacy practice trends—subscribe to Pharmacy Times for weekly clinical insights.
