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ing are usually mild to moderate and can be reduced with appropriate antiemetics. Other side effects of topotecan include mild paresthesia and diarrhea.
1. C Tamoxifen. This patient is premenopausal with a breast cancer expressing hormone receptors (ER and PR positive). She may benefit from interventions aimed at decreasing estrogenic stimulus to the cancer tissue. Because she expressed an interest in having children, oophorectomy may not be an acceptable option for her. Tamoxifen acts by inhibiting estrogen effects and may be useful in treating this type of breast cancer. Ethinyl estradiol is an estrogenic compound and should be avoided in this patient because it may stimulate the growth of her breast cancer. Letro-zole acts as an aromatase inhibitor to decrease conversion of androgens to estrogens, but it is only indicated for use in women with breast cancer who are postmenopausal. Flutamide and nilu-tamide are antiandrogenic compounds used in the treatment of metastatic prostate cancer.
2. B Hot flashes. Anastrozole is an aromatase inhibitor used to treat metastatic breast cancer in postmenopausal women. It is generally well tolerated, although patients may experience hot flashes and other mild side effects such as diarrhea, headache, and nausea. Severe myelosuppression is unlikely. Elevated transami-nases can occur infrequently in patients with liver metastases, but it is unclear whether these changes resulted from progression of liver metastases or from drug effects. Anastrozole (compared with aminoglutethimide) is a specific inhibitor of aromatase enzymes and does not prevent production of endogenous cortisol, so adrenal insufficiency would not be expected.
1. H All of the above. Alemtuzumab is targeted against the CD52 antigen, which is expressed on many different cell types (including normal and malignant cells). As a result, this agent has been associated with profound immunosuppression, and patients are at high risk for developing opportunistic infections. Use of alemtuzumab
is absolutely contraindicated in patients with active infections. In addition, it is strongly recommended that all patients undergoing treatment with this agent be given prophylactic antibiotics to prevent PCP (i.e., TMP-SMX) and herpes virus infections (i.e., acyclovir). Because alemtuzumab (like all MoAbs) can cause infusion-related reactions, including severe hypersensitivity, patients should receive acetaminophen, antihistamines, and possibly corti-costeroids prior to each infusion to minimize these reactions.
2. D Gemtuzumab ozogamicin. Gemtuzumab ozogamicin contains an MoAb directed against CD33 antigens, which are expressed on immature myeloid cells and leukemic cells. The MoAb is linked to a toxin (calicheamicin), which is released inside the cells once the complex is internalized. Gemtuzumab ozogamicin is approved for treatment of adults with CD33-positive AMI who are greater than 60 years of age who are not considered candidates for standard AML therapy. Rituximab is directed against CD20 antigens and is used for B-cell NHL. Trastuzumab is indicated for metastatic breast
cancer in patients who overexpress Her2/neu, and alemtuzumab is used for refractory chronic lymphocytic leukemia. Daclizumab is an MoAb directed against the IL-2 receptor and is used to prevent rejection in solid organ transplantation.
1. E All of the above. Although imatinib is relatively well tolerated compared with other antineoplastic agents, it does have a number of significant toxicities. It may cause fluid retention and edema so patients should be weighed and monitored regularly for signs of fluid retention. Fluid retention is more common in elderly patients (over 65 years) and in those patients receiving higher doses. Imatinib also may be associated with cytopenias such as neutropenia and thrombocytopenia, especially in patients in accelerated phase or blast crisis. It is recommended that complete blood counts be monitored weekly for the first month, biweekly for the second month, and periodically thereafter. Baseline LFTs are important for two reasons. First, imatinib is metabolized by the liver, and impaired liver function may lead to increased imatinib exposure. Second, hepatotoxicity has been reported in patients treated with imatinib. If patients experience elevated LFTs while on imatinib, dose reduction or treatment interruption may be considered.
2. E Itraconazole. Imatinib is primarily metabolized by the CYP3A4 hepatic enzyme system. Drugs that may inhibit this enzyme (such as ketoconazole, itraconazole, erythromycin, clarithromycin, etc.) may impair clearance of imatinib and result in increased toxicity. Imatinib itself is also a fairly potent inhibitor of the CYP3A4 enzyme and may result in toxicity due to other drugs that are substrates for this enzyme (such as simvastatin, warfarin, benzo-diazepines, etc.). The other medications listed are unlikely to affect the function of CYP3A4 or interact adversely with imatinib.