A patient with Wilms’ tumor is receiving a chemotherapeutic agent that is described as working by intercalating into DNA strands, and that is efficacious regardless of which stage of the cell cycle the tumor cells are in. Which of the following agents best fits this description? (LQ)
|C||Dactinomycin (actinomycin D)|
a. Dactinomycin intercalates between and eventually binds to DNA base pairs. This distortion of the DNA chains makes the DNA an unsuitable template for RNA polymerase, and ultimately RNA and protein synthesis is inhibited. Dactinomycin is phase-nonspecific. It is the drug of choice for Wilm’s tumor and is the 2nd drug for ectopic pregnancy.
b. Anastrozole is a aromatase inhibitor. This is an oral agent used for postmenopausal women with early or advanced breast cancer. In postmenopausal women, the major source of estrogen (which supports growth and replication of estrogen-dependent tumors) is androgens. Those androgens are metabolized by aromatase to estrogens. As a result, anastrozole depletes estrogens and can arrest tumor cell growth.
c. Cytarabine (also called cytosine arabinoside) is a pyrimidine analog (antimetabolite) that is metabolized to the active moiety, ara-CTP. The ara-CTP becomes incorporated into DNA, with the main ultimate effect being; suppression of DNA synthesis. It is highly specific for cells in S-phase.
d. Fluorouracil, also an antimetabolite, inhibits thymidylate synthetase. It is not phase-specific, but its activity depends on cells not being in the G0 stage.
e. Tamoxifen is used for breast cancers. It blocks estrogen receptors on the breast cancer cells (for which the main physiologic agonist is estradiol). Tamoxifen is classified as a selective estrogen receptor modifier (SERM).
f. Although it blocks estrogen receptors on responsive breast cancer cells and is therapeutic for them, it acts as an estrogen receptor agonist in the uterus.
g. Thus, one of the main risks of therapy with tamoxifen is endometrial hyperplasia that may lead to endometrial cancer. Because the drug acts as an estrogen receptor agonist in some tissues and an antagonist in others, risk-benefit ratios must be considered carefully.
h. The beneficial effects in active breast carcinoma may outweigh the risks of inducing endometrial disease. However, the preventative use in the absence of breast cancer has a much lower benefit risk ratio. Therefore, the drug is not recommended to healthy women.