Harris JR et al: Diseases of the Breast, 4th ed. Lippincott Williams & Wilkins, 2009.
Hoppe R et al: Textbook of Radiation Oncology, 3rd ed. Elsevier, 2010.
Kantoff PW et al: Prostate Cancer: Principles and Practice. Lippincott Williams &
Wilkins, 2001.
Kelsen DP et al: Gastrointestinal Oncology: Principles and Practices, 2nd ed. Lippincott Williams & Wilkins, 2007.
Kufe D et al: Cancer Medicine, 7th ed. BC Decker, 2006.
Mendelsohn J et al: The Molecular Basis of Cancer, 3rd ed. Saunders, 2008.
Pass HI et al: Principles and Practice of Lung Cancer: The Official Reference Text of the International Association for the Study of Lung Cancer (IASLC), 4th ed. Lippincott Williams & Wilkins, 2010.
Pizzo PA, Poplack AG: Principles and Practice of Pediatric Oncology, 6th ed. Lippincott Williams & Wilkins, 2010.
Weinberg RA: Biology of Cancer, 2nd ed. Taylor & Francis, 2013.
DeVita VT, Chu E: The history of cancer chemotherapy. Cancer Res 2008;68:8643.
Redmond KM et al: Resistance mechanisms to cancer chemotherapy. Front Biosci 2008;13:5138.
The 5-year survival rate for patients with high-risk stage III CRC is on the order of 25–30%. Because the patient has no symptoms after surgery and has no comorbid illnesses, he would be an appropriate candidate to receive aggressive adjuvant chemotherapy. Adjuvant chemotherapy is usually begun 4–6 weeks after surgery to allow sufficient time for the surgical wound to heal. The usual recommendation would be to administer 6 months of oxaliplatin-based chemo-therapy using either intravenous 5-FU or oral capecitabine as the fluoropyrimidine base in combination with oxaliplatin. Patients with partial or complete deficiency in the enzyme dihydropyrimidine dehydrogenase (DPD) experi-ence an increased incidence of severe toxicity to fluoropy-rimidines in the form of myelosuppression, gastrointestinal toxicity in the form of mucositis and diarrhea, and neu-rotoxicity. This is an autosomal recessive pharmacoge-netic syndrome that is present in up to 10% of the North American population (see Chapter 5). Although mutations in DPD can be identified in peripheral blood mononuclear cells, nearly 50% of patients who exhibit severe 5-FU toxicity do not have a defined mutation in the DPD gene. In addition, such mutations may not result in reduced expres-sion of the DPD protein or in altered enzymatic activity. For this reason, genetic testing is not recommended at this time as part of routine clinical practice. There is now an immu-noassay that can measure 5-FU drug levels in the peripheral blood that can help guide 5-FU dosing even in patients with DPD deficiency.
Douglas F. Lake, PhD & Adrienne D. Briggs, MD
A 45-year-old man with high-risk acute myelogenous leu-kemia undergoes high-dose chemotherapy followed by an allogeneic stem cell transplant from an unrelated donor. He receives tacrolimus and low-dose methotrexate as prophy-laxis for graft-vs-host disease. One month after blood count recovery, he develops a skin rash despite ongoing tacrolimus therapy. A skin biopsy confirms grade II acute graft-vs-host disease. How should this case be pharmacologically man-aged at this point?