American Board of Internal Medicine (ABIM) Certification Practice Exam

Which therapy is often modified by the reduced folate leucovorin during colorectal cancer treatment?

1. Capecitabine

2. Cetuximab

3. 5-FU

4. Pembrolizumab

The correct answer is: 5-FU

The therapy that is often modified by the reduced folate leucovorin during colorectal cancer treatment is 5-FU (fluorouracil). Leucovorin is administered in conjunction with 5-FU to enhance its efficacy. The mechanism behind this combination lies in the role that leucovorin plays in stabilizing the binding of 5-FU to the enzyme thymidylate synthase, which is crucial in DNA synthesis and cell division. By enhancing the activity of 5-FU, leucovorin can lead to increased response rates in patients undergoing treatment for colorectal cancer. In contrast, while capecitabine is a prodrug of 5-FU and shares similar mechanisms, the modification through leucovorin is more directly associated with the administration of 5-FU itself. Cetuximab is a monoclonal antibody targeting the epidermal growth factor receptor and does not require modification by leucovorin. Pembrolizumab, a checkpoint inhibitor, also does not involve leucovorin. Thus, leucovorin's primary role in the context of colorectal cancer therapy relates to the enhancement of 5-FU's pharmacological effects.