Anticancer Drugs — MCQs

Anticancer Drugs Indian Medical PG Practice Questions and MCQs

Question 411: Which of the following is NOT an alkylating agent?

A. Cyclophosphamide
B. Lomustine
C. Busulfan
D. Zalcitabine (Correct Answer)

Explanation: The correct answer is **Zalcitabine**. **1. Why Zalcitabine is the correct answer:** Zalcitabine (ddC) is **not** an alkylating agent; it is a **Nucleoside Reverse Transcriptase Inhibitor (NRTI)** [1]. It is an antiretroviral drug used in the treatment of HIV/AIDS. It works by inhibiting the viral reverse transcriptase enzyme and causing DNA chain termination, rather than by cross-linking DNA strands like alkylating agents [1]. **2. Analysis of Incorrect Options (Alkylating Agents):** * **Cyclophosphamide:** A nitrogen mustard and the most widely used alkylating agent [2][3]. It is a prodrug activated by hepatic CYP450 to form phosphoramide mustard, which cross-links DNA [2][3]. * **Lomustine:** A member of the **Nitrosourea** family [3]. These are highly lipid-soluble alkylating agents that can cross the blood-brain barrier, making them first-line for brain tumors (e.g., glioblastoma). * **Busulfan:** An **Alkyl sulfonate**. It specifically targets the bone marrow and is frequently used in conditioning regimens before bone marrow transplantation. **3. NEET-PG High-Yield Clinical Pearls:** * **Cyclophosphamide:** Associated with **Hemorrhagic Cystitis** due to the metabolite **Acrolein** [2]. This is prevented by aggressive hydration and **MESNA**. * **Busulfan:** Known for causing **Pulmonary Fibrosis** ("Busulfan lung") and hyperpigmentation (Addisonian-like skin darkening). * **Nitrosoureas (Lomustine/Carmustine):** Unique for their CNS penetration; they are used for primary brain malignancies. * **Zalcitabine Side Effect:** The most significant dose-limiting toxicity is **peripheral neuropathy**.

Question 412: All of the following are direct DNA interacting cytotoxic agents except?

A. Melphalan
B. Hydroxyurea (Correct Answer)
C. Carmustine
D. Ifosfamide

Explanation: ### Explanation The core concept in this question is the classification of anticancer drugs based on their mechanism of action: **Direct DNA-damaging agents** vs. **Antimetabolites**. **Why Hydroxyurea is the Correct Answer:** Hydroxyurea is an **antimetabolite** that acts as a **Ribonucleotide Reductase inhibitor**. It prevents the conversion of ribonucleotides to deoxyribonucleotides, thereby depleting the building blocks of DNA synthesis. It does not physically bind to or damage the DNA strand itself; rather, it inhibits the *synthesis* of new DNA. It is specifically **S-phase active**. **Why the Other Options are Incorrect:** * **Melphalan (Option A):** This is a nitrogen mustard and a classic **Alkylating agent**. It forms covalent bonds with DNA (specifically at the N7 position of guanine), causing cross-linking and direct structural damage. * **Carmustine (Option C):** This is a **Nitrosourea**. Like other alkylating agents, it causes direct DNA cross-linking and carbamoylation of proteins. * **Ifosfamide (Option D):** This is a nitrogen mustard (an analogue of cyclophosphamide). It is a pro-drug that is metabolized to active alkylating species which directly attack DNA. --- ### High-Yield Clinical Pearls for NEET-PG: * **Hydroxyurea Clinical Uses:** It is used in Chronic Myeloid Leukemia (CML), Polycythemia Vera, and notably in **Sickle Cell Anemia** (because it increases the production of **Fetal Hemoglobin/HbF**). * **Nitrosoureas (Carmustine/Lomustine):** These are highly lipid-soluble and cross the blood-brain barrier, making them the drugs of choice for **Brain Tumors (Gliomas)**. * **Ifosfamide Toxicity:** It can cause **Hemorrhagic Cystitis** due to the metabolite **Acrolein**. This is managed with aggressive hydration and **MESNA** (a sulfhydryl compound that neutralizes acrolein). * **Cell Cycle Specificity:** Alkylating agents (Melphalan, Ifosfamide) are **Cell Cycle Non-Specific (CCNS)**, whereas Hydroxyurea is **Cell Cycle Specific (CCS)** for the S-phase.

Question 413: Which of the following parameters is not monitored in a patient on methotrexate therapy?

A. Liver function tests
B. Lung function tests
C. Eye examination (Correct Answer)
D. Hemogram

Explanation: **Explanation:** Methotrexate (MTX) is a folate antimetabolite that inhibits the enzyme **dihydrofolate reductase (DHFR)**. While it is a cornerstone in treating malignancies and autoimmune conditions (like Rheumatoid Arthritis), it carries a significant profile of systemic toxicities. **Why Eye Examination is the Correct Answer:** Unlike drugs such as Hydroxychloroquine (which requires retinal monitoring) or Ethambutol (which causes optic neuritis), **Methotrexate does not typically cause ocular toxicity**. Therefore, routine eye examinations are not a standard part of MTX monitoring protocols. **Why other options are monitored:** * **Liver Function Tests (LFTs):** MTX is hepatotoxic. Chronic use can lead to elevated transaminases, steatosis, and eventually **hepatic fibrosis or cirrhosis**. Baseline and periodic LFTs are mandatory. * **Hemogram (CBC):** As a cytotoxic drug, MTX causes **bone marrow suppression** (myelosuppression), leading to leucopenia, thrombocytopenia, and anemia. Monitoring the CBC is critical to prevent life-threatening pancytopenia. * **Lung Function Tests:** MTX can induce **interstitial pneumonitis** (Methotrexate-induced lung injury) or pulmonary fibrosis. Patients presenting with a dry cough or dyspnea require urgent pulmonary evaluation. **High-Yield Clinical Pearls for NEET-PG:** * **Rescue Therapy:** **Leucovorin (Folinic acid)** is used to "rescue" normal cells from MTX toxicity by bypassing the inhibited DHFR enzyme. * **Nephrotoxicity:** High-dose MTX can precipitate in renal tubules; **vigorous hydration and urinary alkalinization** are required. * **Contraindication:** MTX is highly **teratogenic** (Category X) and must be avoided in pregnancy. * **Antidote for Overdose:** **Glucarpidase** (carboxypeptidase G2) can rapidly reduce toxic plasma MTX levels.

Question 414: Which of the following causes peripheral neuritis?

A. Methotrexate
B. Vincristine (Correct Answer)
C. Busulfan
D. Cyclophosphamide

Explanation: **Explanation:** **Vincristine** is a Vinca alkaloid that acts as a **microtubule inhibitor**. It binds to tubulin and inhibits its polymerization into microtubules, leading to mitotic arrest in the M-phase. Microtubules are not only essential for cell division but are also critical for **axonal transport** in neurons. By disrupting these microtubule tracks, Vincristine interferes with the transport of neurotransmitters and essential proteins along the long axons of peripheral nerves, leading to **dose-limiting peripheral neuropathy (neuritis)**. This typically manifests as symmetrical "glove and stocking" paresthesia, loss of deep tendon reflexes, and motor weakness. **Why other options are incorrect:** * **Methotrexate:** A folate antagonist (antimetabolite) primarily known for bone marrow suppression, mucositis, and hepatotoxicity. It can cause neurotoxicity (leukoencephalopathy) if given intrathecally, but peripheral neuritis is not its hallmark. * **Busulfan:** An alkylating agent (alkyl sulfonate) most famous for causing **pulmonary fibrosis** ("Busulfan lung") and hyperpigmentation (Addisonian-like syndrome). * **Cyclophosphamide:** An alkylating agent (nitrogen mustard) notorious for **hemorrhagic cystitis** due to the metabolite **Acrolein**. It is also highly emetogenic and causes alopecia. **High-Yield Clinical Pearls for NEET-PG:** * **Vincristine vs. Vinblastine:** Remember the mnemonic: **Vincristine** = **C**NS/Nerve toxicity (Peripheral neuropathy); **Vinblastine** = **B**last (Bone marrow suppression). * Vincristine is notably **bone marrow sparing**, making it ideal for combination regimens. * **Fatal Error:** Vincristine is for **Intravenous use ONLY**. Intrathecal administration is fatal due to ascending myeloencephalopathy. * Other anticancer drugs causing peripheral neuropathy: **Paclitaxel** (microtubule stabilizer) and **Cisplatin** (platinum compound).

Question 415: Which of the following is/are used in the hormonal therapy of breast carcinoma?

A. Letrozole
B. Anastrozole
C. Tamoxifen
D. All of the above (Correct Answer)

Explanation: Hormonal therapy is a cornerstone in the management of hormone receptor-positive (ER/PR+) breast cancer. The goal is to either block estrogen receptors or decrease circulating estrogen levels. **Explanation of Options:** * **Tamoxifen (Option C):** This is a **Selective Estrogen Receptor Modulator (SERM)**. It acts as a competitive antagonist at estrogen receptors in breast tissue, making it the gold standard for pre-menopausal women. It also has agonist effects on the bone (preventing osteoporosis) and endometrium (increasing the risk of endometrial carcinoma). * **Letrozole and Anastrozole (Options A & B):** These are **Third-generation Aromatase Inhibitors (AIs)**. They inhibit the enzyme aromatase, which converts peripheral androgens into estrogens. Since they cannot stop ovarian estrogen production, they are primarily used in **post-menopausal women**. **Why "All of the above" is correct:** All three drugs are FDA-approved and standard-of-care agents used to treat or prevent the recurrence of breast carcinoma by targeting the estrogen signaling pathway. **High-Yield Clinical Pearls for NEET-PG:** 1. **Drug of Choice:** Tamoxifen is preferred in pre-menopausal women; Aromatase Inhibitors (Letrozole/Anastrozole) are preferred in post-menopausal women. 2. **Side Effects:** Tamoxifen increases the risk of **thromboembolism** and **endometrial cancer**. Aromatase inhibitors are associated with an increased risk of **osteoporosis** and joint pain. 3. **Fulvestrant:** A Selective Estrogen Receptor Downregulator (SERD) used in tamoxifen-resistant cases. 4. **Trastuzumab:** Not a hormonal agent, but a monoclonal antibody used for HER2/neu positive breast cancer.

Question 416: Which of the following is the main mechanism by which mechlorethamine exerts its cell killing?

A. Alkylating DNA, causing cross-links between parallel DNA strands (Correct Answer)
B. Blocking microtubular assembly and mitosis during M-phase
C. Inhibiting topoisomerase, preventing repair of DNA strand breaks
D. Intercalating in DNA strands, thereby preventing DNA replication by mRNA

Explanation: **Explanation:** **Mechlorethamine** is the prototype of the **Nitrogen Mustards**, which belong to the class of **Alkylating Agents**. These drugs are cell-cycle non-specific (CCNS) but are most effective during the late G1 and S phases. 1. **Mechanism of Action (Option A):** Mechlorethamine undergoes an intramolecular cyclization to form a highly reactive **ethyleniminium ion**. This intermediate acts as an electrophile that attaches an alkyl group to the **N7 position of Guanine** in DNA. Because mechlorethamine is bifunctional (has two reactive groups), it can bind to two different guanine bases, primarily causing **inter-strand cross-linking**. This prevents the separation of DNA strands, inhibiting replication and transcription, ultimately leading to apoptosis. 2. **Analysis of Incorrect Options:** * **Option B:** This describes **Vinca Alkaloids** (e.g., Vincristine, Vinblastine), which bind to tubulin and inhibit microtubule polymerization. * **Option C:** This describes **Topoisomerase inhibitors** such as Etoposide (Topoisomerase II) or Irinotecan (Topoisomerase I). * **Option D:** This describes **Antitumor Antibiotics** (e.g., Doxorubicin, Dactinomycin), which intercalate between base pairs. Note: mRNA is involved in translation, not DNA replication. **High-Yield NEET-PG Pearls:** * **MOPP Regimen:** Mechlorethamine was historically a key component of the MOPP regimen for **Hodgkin’s Lymphoma** (Mechlorethamine, Oncovin, Procarbazine, Prednisone). * **Vesicant Property:** It is a potent vesicant; accidental extravasation causes severe tissue necrosis. Sodium thiosulfate is used as an antidote. * **Dose-limiting toxicity:** Bone marrow suppression (myelosuppression).

Question 417: Imatinib is used in the treatment of which of the following conditions?

A. Chronic myelomonocytic leukemia
B. Myelodysplastic syndrome
C. Acute lymphoblastic leukemia
D. Gastrointestinal stromal tumors (Correct Answer)

Explanation: **Explanation:** **Imatinib** is a revolutionary targeted therapy that acts as a selective **tyrosine kinase inhibitor (TKI)** [4]. Its primary mechanism involves inhibiting the Bcr-Abl tyrosine kinase, but it also potently inhibits the **c-KIT (CD117)** and **PDGFR** (Platelet-Derived Growth Factor Receptor) tyrosine kinases [1], [5]. 1. **Why Option D is correct:** Gastrointestinal Stromal Tumors (GIST) are characterized by the overexpression of the **c-KIT receptor tyrosine kinase** (in ~95% of cases). Imatinib binds to the ATP-binding site of the c-KIT receptor, blocking downstream signaling and tumor proliferation [2], [5]. It is the first-line medical treatment for metastatic or unresectable GIST. 2. **Why other options are incorrect:** * **Chronic Myelomonocytic Leukemia (CMML):** While Imatinib is the gold standard for Chronic *Myeloid* Leukemia (CML), it is not the standard for CMML, which often requires hypomethylating agents like Azacitidine. * **Myelodysplastic Syndrome (MDS):** MDS is typically treated with Lenalidomide or supportive care; Imatinib has no role unless a specific PDGFR rearrangement is present (rare). * **Acute Lymphoblastic Leukemia (ALL):** Imatinib is only used in the specific subtype of **Philadelphia chromosome-positive (Ph+) ALL** [3]. It is not a general treatment for all ALL cases. **High-Yield Clinical Pearls for NEET-PG:** * **Drug of Choice (DOC):** Chronic Myeloid Leukemia (CML) – targets the Philadelphia chromosome $t(9;22)$ [4]. * **Mechanism:** Competitive inhibition of the ATP-binding site [2]. * **Side Effects:** Fluid retention (periorbital edema), muscle cramps, and hepatotoxicity. * **Resistance:** Often occurs due to point mutations in the kinase domain (e.g., **T315I mutation**), which requires second-generation TKIs like **Dasatinib** or **Nilotinib** [3].

Question 418: All of the following statements about methotrexate are true EXCEPT:

A. It is cell cycle specific and kills cells in the S phase.
B. Its toxicity primarily affects bone marrow and epithelial structures.
C. Folic acid reverses its toxic effects. (Correct Answer)
D. It is the drug of choice for choriocarcinoma.

Explanation: ### Explanation **1. Why Option C is the correct (False) statement:** Methotrexate (MTX) is a folate antagonist that works by inhibiting the enzyme **Dihydrofolate Reductase (DHFR)**. This prevents the conversion of dihydrofolate to tetrahydrofolate (THF). Once MTX binds to DHFR, the cell’s pool of active folate is depleted. Administering **Folic acid** is ineffective because it also requires DHFR to be converted into its active form. To reverse MTX toxicity, we must provide **Folinic acid (Leucovorin/Citrovorum factor)**, which is already a reduced form of folate (N5-formyl-THF) that bypasses the inhibited enzyme. This is known as **"Leucovorin Rescue."** **2. Analysis of other options:** * **Option A:** MTX is a classic **Antimetabolite**. These drugs are **Cell Cycle Specific (CCS)** and act specifically during the **S-phase** by inhibiting DNA synthesis. * **Option B:** Like most cytotoxic drugs, MTX targets rapidly dividing cells. Its primary dose-limiting toxicities include **Bone Marrow Suppression** (myelosuppression) and damage to **Epithelial structures** (leading to oral mucositis and GI ulceration). * **Option D:** MTX is highly effective against trophoblastic tumors and remains the **Drug of Choice for Choriocarcinoma**, often achieving a 100% cure rate in low-risk cases. **3. NEET-PG High-Yield Clinical Pearls:** * **Resistance:** Occurs via decreased drug uptake, decreased polyglutamation, or altered DHFR with lower affinity for MTX. * **Excretion:** MTX is primarily excreted renally. **Salicylates and Sulfonamides** can displace MTX from plasma proteins and inhibit its renal secretion, leading to fatal toxicity. * **Other Uses:** Low-dose MTX is a first-line **Disease-Modifying Antirheumatic Drug (DMARD)** for Rheumatoid Arthritis and is used in Ectopic Pregnancy. * **Specific Toxicity:** Long-term use can lead to **Hepatic Fibrosis/Cirrhosis**.

Question 419: Leucovorin is used to decrease the toxicity of which of the following drugs?

A. Methotrexate (Correct Answer)
B. 6-Mercaptopurine
C. Thio-TEPA
D. Cytosine arabinoside

Explanation: **Explanation:** **1. Why Methotrexate is Correct:** Methotrexate (MTX) is a folate antagonist that inhibits the enzyme **Dihydrofolate Reductase (DHFR)**. [1] This inhibition prevents the conversion of dihydrofolate to tetrahydrofolate (THF), the active form of folic acid required for DNA synthesis. [3] **Leucovorin (Folinic Acid)** is a reduced form of folate that does not require DHFR for activation. [1] When administered after high-dose MTX, it bypasses the blocked enzyme to provide a source of THF for healthy cells, effectively "rescuing" them from bone marrow and GI toxicity. [3] This process is known as **Leucovorin Rescue.** [4] **2. Why Other Options are Incorrect:** * **6-Mercaptopurine (6-MP):** This is a purine antimetabolite. Its toxicity is managed by dose reduction, especially when co-administered with Allopurinol (which inhibits its metabolism by Xanthine Oxidase). [2] * **Thio-TEPA:** This is an alkylating agent. Its primary toxicity is myelosuppression, which is managed with supportive care or growth factors (G-CSF), not Leucovorin. * **Cytosine Arabinoside (Cytarabine):** This is a pyrimidine antagonist. Its dose-limiting toxicity is bone marrow suppression and cerebellar ataxia; Leucovorin has no role in its metabolic pathway. **3. High-Yield Clinical Pearls for NEET-PG:** * **Potentiation:** While Leucovorin *decreases* MTX toxicity, it is used to *increase* the efficacy of **5-Fluorouracil (5-FU)** by stabilizing the binding of 5-dUMP to thymidylate synthase. * **Glucarpidase:** An alternative for MTX toxicity in patients with renal failure; it enzymatically cleaves MTX into inactive metabolites. * **Timing:** Leucovorin rescue must be started within 24–42 hours of MTX administration to be effective.

Question 420: Which of the following drugs cause metaphase arrest?

A. Vincristine, Paclitaxel, Colchicine (Correct Answer)
B. Griseofulvin, Vincristine, Paclitaxel
C. Griseofulvin, Paclitaxel, Etoposide
D. Vincristine, Etoposide, Colchicine

Explanation: ### Explanation **1. Mechanism of Metaphase Arrest** Metaphase arrest occurs when drugs interfere with the **mitotic spindle apparatus**, preventing the separation of sister chromatids. This triggers the "spindle assembly checkpoint," halting the cell cycle in the **M-phase (Metaphase)**. * **Vinca Alkaloids (Vincristine/Vinblastine):** These bind to tubulin and **inhibit polymerization**, preventing the formation of microtubules ("Spindle poisons"). * **Taxanes (Paclitaxel/Docetaxel):** These bind to tubulin and **enhance polymerization**, stabilizing microtubules and preventing their disassembly ("Spindle stabilizers"). * **Colchicine:** Primarily used in gout, it also inhibits microtubule polymerization, leading to metaphase arrest. **2. Analysis of Incorrect Options** * **Option B & C (Griseofulvin):** While Griseofulvin is an antifungal that interferes with microtubule function, it is **not** classified as a standard anticancer drug. Furthermore, Option C includes Etoposide. * **Option C & D (Etoposide):** Etoposide is a **Topoisomerase II inhibitor**. It acts primarily in the **S and G2 phases** of the cell cycle, not the M-phase. It causes DNA strand breaks rather than spindle interference. **3. NEET-PG High-Yield Pearls** * **Cell Cycle Specificity:** Vincas and Taxanes are **M-phase specific**. * **Dose-Limiting Toxicities:** * **Vincristine:** Peripheral neuropathy (Areflexia, paralytic ileus). Note: It is relatively bone marrow sparing. * **Vinblastine:** Bone marrow suppression ("Blast" the marrow). * **Paclitaxel:** Hypersensitivity reactions (pre-treat with dexamethasone/antihistamines) and neuropathy. * **Other M-phase inhibitors:** Ixabepilone (Epothilones) and Eribulin.

Practice by Chapter

Principles of Cancer Chemotherapy

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Alkylating Agents

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Antimetabolites

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Antitumor Antibiotics

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Plant Alkaloids

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Topoisomerase Inhibitors

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Hormonal Agents

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Targeted Therapy

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Immunotherapy

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Management of Chemotherapy Side Effects

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