Page 990 - Basic _ Clinical Pharmacology ( PDFDrive )

976 SECTION VIII Chemotherapeutic Drugs

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Wilkins, 2001.

C ASE STUD Y ANSWER

The 5-year survival rate for patients with high-risk stage III toxicity in the form of mucositis and diarrhea, and neu-
CRC is on the order of 25–30%. Because the patient has rotoxicity. This is an autosomal recessive pharmacoge-
no symptoms after surgery and has no comorbid illnesses, netic syndrome that is present in up to 10% of the North
he would be an appropriate candidate to receive aggressive American population (see Chapter 5). Although mutations
adjuvant chemotherapy. Adjuvant chemotherapy is usually in DPD can be identified in peripheral blood mononuclear
begun 4–6 weeks after surgery to allow sufficient time for the cells, nearly 50% of patients who exhibit severe 5-FU
surgical wound to heal. The usual recommendation would toxicity do not have a defined mutation in the DPD gene. In
be to administer 6 months of oxaliplatin-based chemo- addition, such mutations may not result in reduced expres-
therapy using either intravenous 5-FU or oral capecitabine as sion of the DPD protein or in altered enzymatic activity. For
the fluoropyrimidine base in combination with oxaliplatin. this reason, genetic testing is not recommended at this time
Patients with partial or complete deficiency in the as part of routine clinical practice. There is now an immu-
enzyme dihydropyrimidine dehydrogenase (DPD) experi- noassay that can measure 5-FU drug levels in the peripheral
ence an increased incidence of severe toxicity to fluoropy- blood that can help guide 5-FU dosing even in patients with
rimidines in the form of myelosuppression, gastrointestinal DPD deficiency.