Oncology Pharmacy Consults:
Updates on the Management of Metastatic Colorectal Cancer


Colorectal cancer (CRC) is the third leading cause of cancer among men (following prostate and lung cancers) and women (following breast and lung cancers), accounting for nearly 135 000 new cancer cases in 2016.1 CRC is also the third leading cause of cancer-related mortality for both women and men, with an estimated 49 190 deaths from CRC in 2016. The high rate of CRC-related mortality in the United States is at least partly due to the underuse of effective screening techniques.1 Guidelines from the American Cancer Society recommend that CRC screening should begin at age 50 for men and women at normal cancer risk. Many screening tests are available all of which can detect CRC at early stages. These techniques include fecal occult blood test (which is recommended annually), stool DNA tests (recommended every 3 years), flexible sigmoidoscopy (recommended every 5 years), double-contrast barium enema (recommended every 5 years), colonoscopy (recommended every 10 years), or computed tomography (CT) colonography (recommended every 5 years).1

Surgery is the most common treatment for patients with early-stage colorectal tumors that have not spread. For cancer that has deeply penetrated the bowel wall or spread to the lymph nodes, treatment options may include surgery combined with systemic therapy before (neoadjuvant) or after (adjuvant) surgery, or chemotherapy combined with radiation.1-3 The prognosis for patients with CRC is generally favorable when diagnosed early, with 5-year survival rates of approximately 90% for patients diagnosed with local disease and 71% for those with regional disease. However, approximately 20% of patients have metastatic CRC (mCRC) at the time of diagnosis, while about half of those diagnosed with early-stage disease will eventually progress to mCRC.4-5 Most patients with mCRC have unresectable tumors, and the 5-year survival for these patients is only 13%.1,6

Chemotherapy regimens based on 5-fluorouracil (5-FU), oxaliplatin, and irinotecan have been the mainstay of treatment of patients with mCRC for the last 2 decades.7-8 Common regimens include: 5-FU, leucovorin, and oxaliplatin (FOLFOX); 5-FU, leucovorin, and irinotecan (FOLFIRI); capecitabine and oxaliplatin (XELOX); and variations of these regimens. Some regimens may be administered using different dosing procedures and injection schedules (eg, FOLFOX-4, FOLFOX-6, and FOLFOX-7 regimens, which use varying dosing regimens of 5-FU, leucovorin, and oxaliplatin).8 More recently, the addition of targeted agents has been an important advance in the care of patients with mCRC. Principal targeted therapy options in patients with mCRC include cetuximab and panitumumab, both of which are monoclonal antibodies that bind to epidermal growth factor receptor (EGFR); and bevacizumab, a monoclonal antibody that binds to vascular endothelial growth factor (VEGF).8 These agents are designed to block cellular and molecular mechanisms that are important in tumor transformation and proliferation and to inhibit angiogenesis that is required for continued tumor growth.2 Although these strategies have been shown to improve overall survival (OS) and other outcomes in patients with mCRC, nearly all patients eventually progress on first-line therapy.2 The long-term prognosis for patients with disease progression despite therapy is poor, and new and more effective strategies are needed to improve clinical outcomes for these patients.9

Pharmacists provide many important services in caring for patients with mCRC, including developing treatment strategies, identifying and managing adverse events (AEs), performing long-term monitoring, and ensuring that patients remain adherent to oral therapies. This activity provides an update for pharmacists on the role of newer targeted agents in the management of patients with mCRC.