Devita, Hellman, and Rosenberg's Cancer

LWBK1006-20 LWW-Govindan-Review December 12, 2011 19:4

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

consistent with 5FU-related toxicities. Furthermore, irinotecan ther-

apy would not have been given to this patient with stage III colon

cancer.

Answer 20.5.8. The answer is E.

SN-38 is the active metabolite of irinotecan and is 100- to 1000-fold

more potent than irinotecan as a topoisomerase I inhibitor. Glu-

curonidation is the principal elimination pathway for SN-38. UDP-

glucuronosyltransferase 1 family polypeptide A1 mediates this glu-

curonidation of irinotecan encoded by the UGT1A1 gene. Patients who

are homozygous for the UGT1A1*28 allele glucuronidate SN-38 less effi-

ciently than patients who have one or two wild-type alleles; therefore,

homozygous patients are exposed to higher plasma concentrations of

SN-38 and are thus at a greater risk for severe neutropenia.

Answer 20.5.9. The answer is D.

The results of the German Rectal Cancer Study published by Sauer

et al. confirmed the benefit of neoadjuvant prolonged course RT with

5FU-based chemotherapy for patients with T3+/N0-2 rectal cancer.

Although overall survival was similar for patients treated with neoad-

juvant chemoradiotherapy compared with those treated with postoper-

ative chemoradiotherapy, local recurrence rates and toxicities are more

favorable with neoadjuvant chemoradiotherapy.

Answer 20.5.10. The answer is A.

Transanal excision should only be considered for select patients with

early-stage rectal cancer with the following characteristics: small rectal

cancers less than 3 cm; well to moderately differentiated T1 tumors within

8 cm from the anal verge and limited to less than 30% of the rectal cir-

cumference with no evidence of nodal metastases. Only patient A meets

all of these criteria.

Answer 20.5.11. The answer is A.

After transanal resection of appropriately selected patients with early-

stage rectal cancer, no further therapy is recommended.

Answer 20.5.12. The answer is A.

MYH-associated polyposis is an autosomal-recessive disease affecting the

MYH gene, a base-excision repair gene. A deficiency in MYH leads to

somatic, not germ line, mutations in the APC gene. Thus, clinical features

of patients with MYH-associated polyposis are similar to FAP.

Answer 20.5.13. The answer is D.

The standard therapy for early localized squamous carcinoma of the anus

is chemoradiation with 5FU and mitomycin. This is associated with excel-

lent cure rates. Salvage APR is reserved for recurrent anal cancer.