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Infection prophylaxis: The risk of febrile neutropenia with this regimen is 10 to 20 percent [1] ; primary prophylaxis with hematopoietic growth factors should be considered on an individual basis, particularly for high-risk patients such as those with preexisting neutropenia, advanced disease, poor performance status, or patients over age 65 years. Refer to UpToDate topic on "Use of granulocyte colony stimulating factors in patients with chemotherapy-induced neutropenia". •

Dose adjustment for baseline liver or renal dysfunction: Adjustment of initial cyclophosphamide, doxorubicin, and vincristine doses may be needed for preexisting liver dysfunction [2-4] . In addition, dose adjustment of cyclophosphamide may be required for renal dysfunction. Refer to UpToDate topics on "Chemotherapy hepatotoxicity and dose modification in patients with liver disease" and "Chemotherapy-related nephrotoxicity and dose modification in patients with renal insufficiency". •

Cardiac screening: LVEF should be evaluated prior to initiation of therapy. Dose alterations should be considered for LVEF <50 percent, and doxorubicin therapy is contraindicated in patients with LVEF <30 percent at initiation. Infusion times and schedule may be adjusted to decrease the risk of cardiotoxicity in individuals at high risk for its development. Refer to UpToDate topic on "Cardiotoxicity of anthracycline-like chemotherapy agents". Monitoring parameters: • CBC with differential and platelet count weekly during treatment. • Assess basic metabolic panel (creatinine and electrolytes) and liver function prior to each subsequent treatment cycle. • LVEF should be evaluated periodically based on LVEF at initiation of therapy and cumulative dose of doxorubicin. Refer to UpToDate topic on "Cardiotoxicity of anthracycline-like chemotherapy agents". Suggested dose alterations for toxicity: •

Myelosuppression: Treatment should be delayed until ANC is greater than 1000/mm 3 and platelet count is greater than 100,000/mm 3 . If a patient develops grade 4 (ANC <500) neutropenia or febrile neutropenia with any cycle, HGF support is added to the regimen for subsequent cycles. If grade 4 neutropenia or febrile neutropenia occurs despite HGF support, or if the patient develops grade 3 (25,000 to 50,000 platelets) or 4 (<25,000 platelets) thrombocytopenia with any cycle, the doses of cyclophosphamide and doxorubicin should be decreased by 50 percent for subsequent cycles. •

Neuropathy: Dose adjustment of vincristine may be necessary if the severity of neuropathy persists or worsens. No specific guidelines are available for dose adjustments. If there is a change in body weight of at least 10 percent, dose should be recalculated for all drugs. This table is provided as an example of how to administer this regimen; there may be other acceptable methods. This regimen must be administered by a clinician trained in the use of chemotherapy. The clinician is expected to use his or her independent medical judgment in the context of individual circumstances to make adjustments, as necessary. IV: intravenous; LVEF: left ventricular ejection fraction; CBC: complete blood count; ANC: absolute neutrophil count; HGF: hematopoietic growth factor. * Many prospective studies have dosed prednisone by body surface area with doses ranging from 40 mg/m 2 /day to 100 mg/m 2 /day; however, many institutions use the 100 mg/day dosing listed for convenience without apparent loss in efficacy. References: Simon A, et al. Br J Haematol 2010; 151:159. Cytoxan (cyclophosphamide) injection. US FDA-approved manufacturer's package insert. US National Library of Medicine. (Available online at dailymed.nlm.nih.gov, accessed on January 10, 2012). Adriamycin (doxorubicin hydrochloride) injection. US FDA-approved manufacturer's package insert. US National Library of Medicine. (Available online at dailymed.nlm.nih.gov, accessed on January 10, 2012). Vincristine (vincristine sulfate) injection. US FDA-approved product information. US National Library of Medicine. (Available online at dailymed.nlm.nih.gov, accessed on January 10, 2012).