LWBK1006-11 LWW-Govindan-Review November 24, 2011 11:21
Chapter 11•Systemic Therapy for Cancer 129ANSWERS
Answer 11.1. The answer is B.
Patients who are homozygous for the triple repeat polymorphism were
found to have two- to fourfold greater gene expression compared to
double repeat polymorphism. This increase in gene expression results in
increased TS levels. There is an inverse relationship between TS levels and
5-FU response; therefore, patients with higher TS levels were less likely
to respond to 5-FU.Answer 11.2. The answer is C.
A prognostic marker is a genetic or molecular variation that would affect
the natural history of the disease. In patients who have stage II colon can-
cer, a deficiency in MMR protein expression would lead to a more favor-
able natural course of disease and would diminish the effect of adjuvant
chemotherapy. Predictive markers are more commonly seen for predic-
tion of the likelihood of response or toxicity from a specific drug, such as
KRAS mutations leading to diminished response from cetuximab.Answer 11.3. The answer is A.
Methotrexate is predominately renally cleared with about 80% to 90%
excreted unchanged in the urine. Excretion is directly related to crea-
tinine clearance, so patients with an elevated serum creatinine should
either avoid methotrexate or receive a reduced dose. The renal excretion
of methotrexate can be inhibited by medications such as probencid, peni-
cillins, cephalosporins, aspirin, and NSAIDs, so these drugs need to be
avoided concomitantly with methotrexate. Methotrexate distributes into
third-spaces such as pleural effusions and ascites. This can cause delayed
drug clearance. While methotrexate can cause elevations in bilirubin and
transaminases, there are no dose reduction recommendations for bilirubin
less than 3 mg/dL.Answer 11.4. The answer is D.
Leucovorin rescue is designed to provide reduced folate to normal cells
and minimize the toxicity from methotrexate. This should be started
about 24 hours after the infusion of methotrexate and continued until
the methotrexate has cleared. Vigorous intravenous hydration is impor-
tant with methotrexate, but this should also include sodium bicarbon-
ate in order to help facilitate urine alkalinization. When the urine is
acidic, methotrexate and its metabolites can precipitate within the tubules
causing nephrotoxicity. Folic acid supplementation is not necessary for
methotrexate infusions.Answer 11.5. The answer is C.
With both pemetrexed and pralatrexate, supplementation with Vitamin
B 12 and folic acid is required to minimize hematologic toxicities. Vitamin