Devita, Hellman, and Rosenberg's Cancer

LWBK1006-11 LWW-Govindan-Review November 24, 2011 11:21

132 DeVita, Hellman, and Rosenberg’s CANCER: Principles and Practice of Oncology Review

homologous recombination, loss of repair mechanisms, and cell death.

PARP inhibition has also been implicated in decreased production of

hypoxia-inducible factor-1 function that may contribute to cancer cell

death.

Answer 11.18. The answer is C.

Pulmonary toxicities are a relatively rare event in patients taking

everolimus, occurring in less than 1% of patients. Dry skin with an

acneiform rash is one of the most common side effects of everolimus

therapy seen in up to 18% of patients. Deep vein thrombosis has been

reported in 1% to 10% of patients taking everolimus, but no recommen-

dations exist for prophylactic anticoagulation. Rates of endocrine and

other metabolic adverse events (including hypercholesterolemia, hyper-

triglyceridemia, and hyperglycemia) with everolimus have been as high

as 90%.

Answer 11.19. The answer is D.

Asparaginase has been shown to antagonize the cytotoxic antimetabolite

activity of methotrexate when administered either concurrently with or

immediately before the drug. The proposed mechanism is via decreased

methotrexate polyglutamation leading to lower levels of unbound intra-

cellular drug. It is recommended, therefore, that the two drugs be given

sequentially at least 24 hours apart.

Answer 11.20. The answer is C.

The biologic effects seen with interferons are associated with interactions

with both the innate and adaptive immune systems. Anorexia and weight

loss are commonly seen with higher dose regimens, such as those used for

malignant melanoma. While not studied extensively, no clinically signifi-

cant drug–drug interactions have been proven for interferons to date.

Answer 11.21. The answer is A.

High-dose interferon therapy can cause acute elevations in serum

transaminases. This toxicity may result in fatal hepatic failure. Dose

reductions have been recommended in the setting of transaminitis that

have allowed for safe continued administration of the drug.

Answer 11.22. The answer is B.

Delayed, prolonged, and severe cytopenias have been reported with ibri-

tumomab therapy. It is recommended that therapy not be administered to

patients with greater than or equal to 25% lymphoma marrow involve-

ment or to patients with prior stem cell mobilization failure.

Answer 11.23. The answer is C.

Doses of IL-2 should be withheld or interrupted for toxicities; doses

should not be reduced. It is recommended that treatment be with-

held for patients with moderate-to-severe lethargy or somnolence, as