Drugs for Cancer

Question 1

Which of the following is a dose-limiting toxicity associated with platinum compounds such as cisplatin?

A. Myelosuppression
B. Cardiotoxicity
C. Nephrotoxicity
D. Hepatotoxicity

Answer 1

Correct Answer: C. Nephrotoxicity
Explanation: Nephrotoxicity is the dose-limiting toxicity of platinum compounds, including cisplatin. These agents can cause renal damage through direct tubular injury. Although other toxicities such as neurotoxicity and ototoxicity occur, they are not dose-limiting.

A. Myelosuppression: A common dose-limiting toxicity of many chemotherapeutic agents, particularly anthracyclines (e.g., doxorubicin) and etoposide. While platinum compounds can cause myelosuppression, it is not dose-limiting for cisplatin.
B. Cardiotoxicity: Primarily associated with anthracyclines, such as doxorubicin, which can cause cumulative dose-dependent cardiomyopathy. Platinum compounds are not known for significant cardiotoxic effects.
D. Hepatotoxicity: Associated with drugs like methotrexate, which can cause hepatic fibrosis or cirrhosis at higher doses. Cisplatin and carboplatin rarely cause significant liver damage.

Question 2

Which category of antineoplastic drugs works by inhibiting thymidylate synthase, leading to “thymineless death”?

A. Alkylating agents
B. Platinum compounds
C. Inhibitors of ribonucleotide reductase
D. Inhibitors of thymidylate synthase

Answer 2

Correct Answer: D. Inhibitors of thymidylate synthase
Explanation: Thymidylate synthase inhibitors, such as 5-fluorouracil, interfere with DNA synthesis by depleting thymine, causing cell death. Alkylating agents and platinum compounds work via cross-linking DNA, while ribonucleotide reductase inhibitors block the synthesis of deoxyribonucleotides.

A. Alkylating agents: These drugs, such as cyclophosphamide and ifosfamide, work by adding alkyl groups to DNA, leading to cross-linking and strand breaks rather than directly interfering with thymine synthesis.
B. Platinum compounds: These, including cisplatin and carboplatin, cause DNA damage by forming intrastrand cross-links, not by inhibiting thymidylate synthase.
C. Inhibitors of ribonucleotide reductase: Drugs like gemcitabine target an earlier step in nucleotide synthesis by preventing the conversion of ribonucleotides to deoxyribonucleotides. They don’t directly inhibit thymidylate synthase.

Question 3

Which phase of the cell cycle is specifically targeted by antineoplastic drugs classified as cell-cycle specific?

A. G0 phase
B. M phase
C. G1 phase
D. S phase

Answer 3

Correct Answer: D. S phase
Explanation: Cell-cycle-specific drugs primarily target the S phase, where DNA synthesis occurs. Non-specific drugs, by contrast, can act on cells regardless of their position in the cell cycle.

A. G0 phase: This is the resting phase where cells are metabolically active but not dividing. Drugs like alkylating agents are effective regardless of the cell cycle phase and can affect cells in G0.
B. M phase: Drugs such as vinca alkaloids (e.g., vincristine) and taxanes (e.g., paclitaxel) specifically target the mitotic (M) phase by interfering with microtubule dynamics.
C. G1 phase: Drugs like asparaginase (used in leukemia) can target this phase by depleting asparagine, essential for protein synthesis in certain cells.

Question 4

Which antineoplastic drug is an orally bioavailable prodrug of 5-fluorouracil?

A. Gemcitabine
B. Capecitabine
C. Pemetrexed
D. Cyclophosphamide

Answer 4

Correct Answer: B
Explanation: Capecitabine is a prodrug of 5-fluorouracil, converted in the liver to its active form. Gemcitabine is a ribonucleotide reductase inhibitor, pemetrexed is a folate analogue, and cyclophosphamide is an alkylating agent.

A. Gemcitabine: This is a ribonucleotide reductase inhibitor, used intravenously, and is unrelated to 5-fluorouracil metabolism.
C. Pemetrexed: A folate analogue that inhibits thymidylate synthase but is not a prodrug of 5-fluorouracil. It is used in non-small cell lung cancer.
D. Cyclophosphamide: This alkylating agent is a prodrug but acts by DNA cross-linking after activation in the liver, unrelated to thymidylate synthesis or 5-fluorouracil.

Question 5

What is the primary mechanism of action for alkylating agents like cyclophosphamide?

A. Inhibiting thymidylate synthase
B. Cross-linking DNA through bis-alkylation
C. Inhibiting ribonucleotide reductase
D. Inducing DNA single-strand breaks

Answer 5

Correct Answer: B
Explanation: Alkylating agents work by attaching alkyl groups to guanine bases in DNA, causing cross-links and preventing DNA replication. This differs from mechanisms such as ribonucleotide reductase inhibition or thymidylate synthase inhibition.

A. Inhibiting thymidylate synthase: This is the mechanism of action for 5-fluorouracil and capecitabine, which interfere with pyrimidine synthesis, not DNA cross-linking.
C. Inhibiting ribonucleotide reductase: This is the mechanism for gemcitabine, which prevents deoxyribonucleotide synthesis required for DNA replication.
D. Inducing DNA single-strand breaks: Topoisomerase inhibitors (e.g., irinotecan for Topoisomerase I) create single-strand breaks during DNA unwinding, not alkylation.

Question 6

Which of the following cancers is most likely to be responsive to DNA-damaging chemotherapy due to the presence of wild-type p53?

A. Pancreatic cancer
B. Lung cancer with p53 mutations
C. Testicular cancer
D. Colon cancer with p53 mutations

Answer 6

Correct Answer: C
Explanation: Testicular cancers and other cancers with wild-type p53 are often highly responsive to DNA-damaging chemotherapy because functional p53 promotes apoptosis in response to DNA damage.

A. Pancreatic cancer: Often has mutated p53, leading to resistance to DNA-damaging agents.
B. Lung cancer with p53 mutations: Similarly, mutated p53 makes DNA repair mechanisms less functional, reducing sensitivity to such agents.
D. Colon cancer with p53 mutations: Mutations in p53 often confer chemotherapy resistance, unlike wild-type p53, which enhances sensitivity by promoting apoptosis.

Question 7

Which of the following is a serious adverse effect unique to oxaliplatin compared to other platinum compounds?

A. Peripheral neuropathy
B. Nephrotoxicity
C. Cold-induced neurotoxicity
D. Myelosuppression

Answer 7

Correct Answer: C
Explanation: Oxaliplatin is associated with cold-induced neurotoxicity, a unique feature not shared by cisplatin or carboplatin. Peripheral neuropathy occurs with all platinum compounds, but the cold sensitivity is specific to oxaliplatin.

A. Peripheral neuropathy: Common to all platinum compounds, but the cold-exacerbated nature is specific to oxaliplatin.
B. Nephrotoxicity: A hallmark of cisplatin, though all platinum compounds have some nephrotoxic potential.
D. Myelosuppression: More commonly associated with carboplatin, which has lower nephrotoxicity than cisplatin but higher bone marrow suppression effects.

Question 8

Which of the following drugs is associated with dose-dependent cardiotoxicity?

A. Doxorubicin
B. Cisplatin
C. Bleomycin
D. Vincristine

Question 9

What is the main adverse effect associated with bleomycin?

A. Nephrotoxicity
B. Cardiotoxicity
C. Myelosuppression
D. Pulmonary fibrosis

Answer 9

Correct Answer: D. Pulmonary fibrosis
Rationale: Bleomycin induces free radical formation, which damages DNA and primarily affects lung tissue, leading to pulmonary fibrosis as the dose-limiting toxicity.

A. Nephrotoxicity: More typical of cisplatin or methotrexate.
B. Cardiotoxicity: Observed with doxorubicin and other anthracyclines.
C. Myelosuppression: Mild with bleomycin compared to its pulmonary effects.

Question 10

Which of the following drugs inhibits Topoisomerase I, resulting in DNA single-strand breaks?

A. Etoposide
B. Cisplatin
C. Irinotecan
D. Gemcitabine

Answer 10

Correct Answer: C. Irinotecan

Rationale: Irinotecan inhibits Topoisomerase I, an enzyme that relieves DNA supercoiling during replication. Its inhibition causes single-strand breaks, leading to apoptosis.
A. Etoposide: Inhibits Topoisomerase II, causing DNA double-strand breaks.
B. Cisplatin: Causes DNA cross-linking, not topoisomerase inhibition.
D. Gemcitabine: Inhibits ribonucleotide reductase, halting DNA synthesis but unrelated to topoisomerases

Question 11

Which antineoplastic drug is most associated with hemorrhagic cystitis?

A. Methotrexate
B. Cyclophosphamide
C. Cisplatin
D. Vinblastinem

Answer 11

Correct Answer: B. Cyclophosphamide

Rationale: Cyclophosphamide is metabolized to acrolein, a toxic metabolite that irritates the bladder mucosa, leading to hemorrhagic cystitis. Co-administration of mesna can help prevent this effect.
A. Methotrexate: Causes hepatotoxicity and myelosuppression, not cystitis.
C. Cisplatin: Causes nephrotoxicity, not bladder-related effects.
D. Vinblastine: Causes bone marrow suppression, not cystitis.

Question 12

What is the primary dose-limiting toxicity of methotrexate?

A. Myelosuppression
B. Peripheral neuropathy
C. Pulmonary fibrosis
D. Nephrotoxicity

Answer 12

A. Myelosuppression

Rationale: Methotrexate inhibits dihydrofolate reductase, disrupting DNA synthesis in rapidly dividing cells like bone marrow, leading to severe myelosuppression.
B. Peripheral neuropathy: Common with vincristine or paclitaxel, not methotrexate.
C. Pulmonary fibrosis: Rarely occurs with methotrexate; more typical of bleomycin.
D. Nephrotoxicity: Seen in cisplatin, but methotrexate can cause renal toxicity at high doses if hydration is inadequate.

Question 13

Which of the following drugs is associated with a high risk of secondary leukemia?

A. Methotrexate
B. Cisplatin
C. Etoposide
D. Bleomycin

Answer 13

Correct Answer: C. Etoposide

Rationale: Etoposide, a Topoisomerase II inhibitor, increases the risk of treatment-related acute myeloid leukemia (AML), especially with prolonged use or high doses.
A. Methotrexate: Linked to hepatotoxicity but not secondary malignancies.
B. Cisplatin: Causes nephro- and ototoxicity, not leukemia.
D. Bleomycin: Causes pulmonary fibrosis but not secondary leukemia.

Question 14

Which drug is most likely to cause ototoxicity?

A. Doxorubicin
B. Cisplatin
C. Methotrexate
D. Vincristine

Answer 14

Which drug is most likely to cause ototoxicity?
Correct Answer: B. Cisplatin

Rationale: Cisplatin accumulates in the cochlea, damaging hair cells and leading to hearing loss, particularly at high frequencies. This ototoxicity is often irreversible.
A. Doxorubicin: Causes cardiotoxicity, not hearing loss.
C. Methotrexate: Associated with hepatotoxicity or renal issues, not ototoxicity.
D. Vincristine: Causes peripheral neuropathy, not ototoxicity.

Question 15

Which drug is used as a rescue agent to reduce methotrexate toxicity?

A. Mesna
B. Amifostine
C. Filgrastim
D. Leucovorin

Answer 15

Correct Answer: D. Leucovorin

Rationale: Leucovorin (folinic acid) bypasses the inhibition of dihydrofolate reductase by methotrexate, replenishing folate stores and rescuing normal cells from methotrexate-induced toxicity.
A. Mesna: Prevents hemorrhagic cystitis caused by cyclophosphamide or ifosfamide.
B. Amifostine: Protects against cisplatin-induced nephrotoxicity, not methotrexate toxicity.
C. Filgrastim: Stimulates neutrophil production to mitigate chemotherapy-induced neutropenia, not specific to methotrexate.

Question 16

Which of the following statements best describes the mechanism of action of anthracyclines?

A. They bind to microtubules and inhibit their depolymerization.
B. They intercalate into DNA and inhibit topoisomerase II function.
C. They inhibit the GTP-binding domain of tubulin, preventing polymerization.
D. They bind to PARP1 and block DNA repair pathways.

Answer 16

Correct Answer: B
Rationale: Anthracyclines, such as doxorubicin, intercalate into DNA and inhibit topoisomerase II, leading to DNA lesions and cell death. They also generate free radicals causing additional DNA and cellular damage.

Rationale for Incorrect Answers:
A) Describes the mechanism of action of taxanes like paclitaxel, which stabilize microtubules, not anthracyclines.
C) Refers to vinca alkaloids, such as vincristine, which inhibit microtubule polymerization by binding tubulin.
D) Refers to PARP1 inhibitors like olaparib, unrelated to anthracyclines.

Question 17

What is a key dose-limiting toxicity associated with doxorubicin?

A) Neurotoxicity
B) Pulmonary toxicity
C) Cardiotoxicity
D) Nephrotoxicity

Answer 17

Correct Answer: C) Cardiotoxicity

Rationale for Correct Answer:
Doxorubicin’s cardiotoxicity is dose-dependent, linked to cumulative exposure, and results from free radical production in cardiac tissue, leading to myocardial damage.

Rationale for Incorrect Answers:

A) Neurotoxicity is commonly associated with drugs like vincristine, not doxorubicin.
B) Pulmonary toxicity is a hallmark of drugs like bleomycin.
D) Nephrotoxicity is most commonly linked to cisplatin, not doxorubicin.

Question 18

Which of the following adverse effects is unique to epirubicin compared to doxorubicin?

A. Alopecia
B. Conjunctivitis
C. Myelosuppression
D. Cardiotoxicity

Answer 18

Correct Answer: B) Conjunctivitis
Rationale for Correct Answer:
Conjunctivitis is a specific adverse effect of epirubicin, distinguishing it from doxorubicin.

Rationale for Incorrect Answers:

A) Alopecia is common to both drugs.
C) Myelosuppression is a shared toxicity between epirubicin and doxorubicin.
D) Both drugs exhibit cardiotoxicity, with doxorubicin being more prominently linked to severe cardiac effects.

Question 19

What is the primary adverse effect associated with epipodophyllotoxins like etoposide?

A. Cardiotoxicity
B. Bone marrow suppression
C. Peripheral neuropathy
D. Hypersensitivity reactions

Answer 19

Correct Answer: B) Bone marrow suppression

Rationale for Correct Answer:
Epipodophyllotoxins cause significant bone marrow suppression due to their effect on rapidly dividing cells by inducing DNA strand breaks.

Rationale for Incorrect Answers:

A) Cardiotoxicity is more characteristic of anthracyclines.
C) Peripheral neuropathy is a common toxicity of vinca alkaloids like vincristine.
D) Hypersensitivity reactions are associated with taxanes like paclitaxel.

Question 20

What is the primary mechanism by which paclitaxel induces cell death?

A. Inhibiting DNA repair pathways by targeting PARP1.
B. Promoting microtubule polymerization and inhibiting depolymerization.
C. Inhibiting topoisomerase II-mediated religation of DNA breaks.
D. Binding to β-tubulin to inhibit microtubule polymerization.

Answer 20

Correct Answer: B) Promoting microtubule polymerization and inhibiting depolymerization.
Rationale for Correct Answer:
Paclitaxel stabilizes microtubules, preventing their disassembly, which disrupts the mitotic spindle and arrests the cell cycle in mitosis, ultimately causing apoptosis.

Rationale for Incorrect Answers:

A) Describes PARP1 inhibitors like olaparib.
C) Refers to anthracyclines like doxorubicin.
D) Describes vinca alkaloids, which inhibit microtubule polymerization.

Question 21

Which of the following is a key distinguishing adverse effect of docetaxel compared to paclitaxel?

A. Peripheral neuropathy
B. Fluid retention
C. Hypersensitivity reactions
D. Pulmonary toxicity

Answer 21

Correct Answer: B) Fluid retention
Rationale for Correct Answer:
Docetaxel is uniquely associated with fluid retention, often requiring premedication with corticosteroids.

Rationale for Incorrect Answers:

A) Peripheral neuropathy is a common adverse effect of both taxanes.
C) Both drugs cause hypersensitivity reactions, often mitigated by premedication.
D) Pulmonary toxicity is rare and not a distinguishing feature of docetaxel.

Question 22

What is the primary clinical use of olaparib?

A. Treatment of EGFR-positive non-small cell lung cancer.
B. Treatment of BRCA1/2 mutation-positive cancers.
C. Treatment of HER2-positive breast cancer.
D. Treatment of ALK-positive non-small cell lung cancer.

Answer 22

Correct Answer: B) Treatment of BRCA1/2 mutation-positive cancers.
Rationale for Correct Answer:
Olaparib is a PARP1 inhibitor specifically effective against BRCA-mutated cancers, including breast, ovarian, prostate, and pancreatic cancers.

Rationale for Incorrect Answers:

A) EGFR-positive cancers are treated with drugs like osimertinib.
C) HER2-positive breast cancer is treated with agents like trastuzumab.
D) ALK-positive cancers are treated with drugs like alectinib.

Question 23

Which of the following statements best describes the mechanism of action of pembrolizumab?

A. It binds to EGFR and inhibits downstream signaling pathways.
B. It binds to ALK and prevents fusion protein formation.
C. It blocks PD-1 on T-cells, restoring immune response against tumors.
D. It inhibits VEGF to prevent tumor angiogenesis.

Answer 23

Correct Answer: C
Rationale for Correct Answer:
Pembrolizumab is a monoclonal antibody that blocks PD-1 (Programmed Death-1) on T-cells. This restores their ability to recognize and attack tumor cells that evade immune detection.

Rationale for Incorrect Answers:

A. Binds to EGFR: EGFR inhibitors, like osimertinib, target epidermal growth factor receptor pathways, not PD-1.
B. Binds to ALK: ALK inhibitors, such as alectinib, prevent ALK fusion protein activity in cancers like ALK-positive lung cancer, unrelated to pembrolizumab’s mechanism.
D. Inhibits VEGF: Anti-VEGF agents (e.g., bevacizumab) target angiogenesis but do not impact PD-1 or immune modulation.

Question 24

Which of the following is a dose-limiting toxicity associated with androgen deprivation therapy (ADT)?

A. Increased bone density
B. Decreased libido
C. Hot flashes
D. Reduced bone density

Answer 24

Correct Answer: D

Rationale for Correct Answer:
ADT reduces bone density over time, increasing the risk of osteoporosis and fractures, making it a critical consideration for patients undergoing prolonged therapy.

Rationale for Incorrect Answers:

A. Increased bone density: This is the opposite of what occurs during ADT, as decreased androgens lead to bone density loss.
B. Decreased libido: While a common adverse effect, it is not considered dose-limiting.
C. Hot flashes: These are frequent but not dose-limiting, as they do not typically compromise overall patient health or therapy continuation.

Question 25

Which of the following adverse effects of ADT contributes to an increased risk of cardiovascular disease?

A. Insulin resistance
B. Increased muscle mass
C. Hypotension
D. Decreased cholesterol levels

Answer 25

Correct Answer: A

Rationale for Correct Answer:
Insulin resistance is a known metabolic effect of ADT, contributing to higher risks of diabetes, hyperlipidemia, and cardiovascular disease.

Rationale for Incorrect Answers:

B. Increased muscle mass: ADT leads to a loss of muscle mass, not an increase.
C. Hypotension: ADT does not typically cause hypotension; cardiovascular risks are related to other factors like lipid changes.
D. Decreased cholesterol levels: ADT can increase blood lipids, not decrease them, which further elevates cardiovascular risk.

More information:
Why ADT Causes Insulin Resistance
Androgen deprivation therapy (ADT) reduces circulating testosterone levels, which play a critical role in regulating body composition and metabolic processes. The key mechanisms by which ADT contributes to insulin resistance are:

Increased Visceral Fat:
Reduced testosterone leads to increased fat deposition, particularly visceral adipose tissue. This type of fat is metabolically active and releases free fatty acids and pro-inflammatory cytokines that interfere with insulin signaling.

Reduced Muscle Mass:
Testosterone supports muscle growth and maintenance. With ADT, muscle mass declines, reducing the body’s capacity to store glucose as glycogen and increasing circulating blood glucose levels, contributing to insulin resistance.

Altered Lipid Metabolism:
ADT can cause unfavorable changes in lipid profiles, such as increased triglycerides and decreased HDL cholesterol, which are associated with insulin resistance and cardiovascular risk.

Systemic Inflammation:
The loss of testosterone’s anti-inflammatory effects can lead to low-grade chronic inflammation, which negatively impacts insulin sensitivity by disrupting signaling pathways in target tissues like the liver, skeletal muscle, and adipose tissue.