Anticancer Drugs — MCQs

Anticancer Drugs Indian Medical PG Practice Questions and MCQs

Question 461: Tretinoin is useful in the treatment of which type of leukemia?

A. M2
B. M3 (Correct Answer)
C. M5
D. M7

Explanation: **Explanation:** **Tretinoin (All-Trans Retinoic Acid or ATRA)** is the standard of care for **Acute Promyelocytic Leukemia (APL)**, which is classified as **M3** under the French-American-British (FAB) system. **Why M3 is correct:** APL (M3) is characterized by a specific chromosomal translocation **t(15;17)**. This translocation fuses the Retinoic Acid Receptor alpha (RARα) gene on chromosome 17 with the Promyelocytic Leukemia (PML) gene on chromosome 15. The resulting **PML-RARα fusion protein** blocks myeloid differentiation at the promyelocyte stage. Tretinoin works by binding to this abnormal receptor, inducing the **differentiation** of leukemic promyelocytes into mature neutrophils, thereby inducing remission. **Why other options are incorrect:** * **M2 (Acute Myeloblastic Leukemia with maturation):** Commonly associated with t(8;21). It does not involve the RARα mutation and does not respond to differentiation therapy with ATRA. * **M5 (Acute Monocytic Leukemia):** Characterized by monocytic lineage; often associated with gum hypertrophy and skin involvement. It is treated with standard induction chemotherapy (7+3 regimen). * **M7 (Acute Megakaryoblastic Leukemia):** Associated with Down Syndrome (in children <5 years) and extensive marrow fibrosis. It does not respond to ATRA. **High-Yield Clinical Pearls for NEET-PG:** * **Differentiation Syndrome:** A life-threatening side effect of ATRA characterized by fever, dyspnea, and pulmonary infiltrates. It is managed with **Dexamethasone**. * **DIC Risk:** M3 is highly associated with **Disseminated Intravascular Coagulation (DIC)** due to the release of procoagulants from promyelocyte granules. * **Arsenic Trioxide:** Also used in M3 to degrade the PML-RARα protein, often in combination with ATRA.

Question 462: Which of the following drugs is known to cause cardiomyopathy?

A. Actinomycin D
B. Doxorubicin (Correct Answer)
C. Mitomycin C
D. Mitoxantrone

Explanation: **Explanation:** **Doxorubicin** is the correct answer because it is a prototype anthracycline antibiotic notorious for causing **cardiotoxicity**. The underlying mechanism involves the formation of iron-anthracycline complexes that generate **reactive oxygen species (ROS)**, specifically superoxide radicals. Since the myocardium is relatively deficient in antioxidant enzymes like catalase and superoxide dismutase, it is highly susceptible to oxidative damage, leading to irreversible dilated cardiomyopathy and congestive heart failure. **Analysis of Options:** * **Actinomycin D (Dactinomycin):** Primarily used for pediatric tumors (Wilms tumor, Ewing sarcoma). Its major dose-limiting toxicity is bone marrow suppression and GI distress, not cardiomyopathy. * **Mitomycin C:** An alkylating agent used for solid tumors. Its hallmark toxicity is **Hemolytic Uremic Syndrome (HUS)** and delayed myelosuppression. * **Mitoxantrone:** While it is an anthracenedione that can cause cardiotoxicity, it is significantly **less cardiotoxic** than Doxorubicin because it does not produce the same level of free radicals. In the context of this question, Doxorubicin is the classic and most potent cause. **High-Yield Clinical Pearls for NEET-PG:** * **Cumulative Dose:** The risk of Doxorubicin-induced heart failure increases significantly once the cumulative dose exceeds **550 mg/m²**. * **Prevention:** **Dexrazoxane**, an iron-chelating agent, is administered to reduce the risk of free radical-induced cardiac damage. * **Monitoring:** Patients on anthracyclines should be monitored using **MUGA scans** or Echocardiography to track the Left Ventricular Ejection Fraction (LVEF). * **Liposomal Doxorubicin:** This formulation is used to reduce cardiac uptake and decrease toxicity.

Question 463: Which antineoplastic drug is a peptide?

A. Bleomycin (Correct Answer)
B. Aspartame
C. Valinomycin
D. Dactinomycin

Explanation: **Explanation:** **Bleomycin** is the correct answer because it is a unique glycopeptide antibiotic derived from *Streptomyces verticillus*. Structurally, it consists of a complex of small peptides and sugars. It functions by binding to DNA and chelating ferrous iron ($Fe^{2+}$), leading to the formation of free radicals that cause single- and double-stranded DNA breaks. **Analysis of Options:** * **Bleomycin (Correct):** A peptide-based antineoplastic agent. It is cell-cycle specific, acting primarily in the **G2 phase**. * **Aspartame:** This is an artificial non-saccharide sweetener (a dipeptide of aspartic acid and phenylalanine). It has no antineoplastic properties. * **Valinomycin:** A depsipeptide antibiotic that acts as a potassium ionophore. While it has biological activity, it is not used as a clinical antineoplastic drug. * **Dactinomycin (Actinomycin D):** While it contains peptide loops (pentapeptide lactones), it is primarily classified as a **chromopeptide** or an intercalating antibiotic. In the context of standard pharmacology exams, Bleomycin is the classic example cited as a "peptide" anticancer drug. **High-Yield Clinical Pearls for NEET-PG:** * **Dose-limiting toxicity:** Unlike most anticancer drugs, Bleomycin is **not** significantly myelosuppressive. Its dose-limiting toxicity is **Pulmonary Fibrosis**. * **Metabolism:** It is inactivated by the enzyme *bleomycin hydrolase*, which is deficient in the lungs and skin, explaining its specific organ toxicities (fibrosis and hyperpigmentation/flagellate dermatitis). * **Clinical Use:** It is a key component of the **ABVD** regimen for Hodgkin’s Lymphoma and the **BEP** regimen for Germ Cell Tumors.

Question 464: To which group of anticancer drugs does temozolomide belong?

A. Oral alkylating agent (Correct Answer)
B. Antitumor antibiotic
C. Antimetabolite
D. Mitotic spindle inhibitor

Explanation: **Explanation:** **Temozolomide** is a second-generation **oral alkylating agent** belonging to the triazene class. It is a prodrug that undergoes spontaneous non-enzymatic hydrolysis at physiological pH to its active metabolite, **MTIC** (monomethyl triazeno imidazole carboxamide) [1]. The mechanism of action involves the addition of methyl groups to DNA, specifically at the **O6 and N7 positions of guanine**, leading to DNA fragmentation and apoptosis [1]. Its high oral bioavailability and ability to cross the **blood-brain barrier (BBB)** make it the gold standard for treating high-grade gliomas. **Why other options are incorrect:** * **Antitumor Antibiotics (e.g., Doxorubicin, Bleomycin):** These are derived from *Streptomyces* species and act primarily through DNA intercalation or inducing free radical damage, not simple alkylation. * **Antimetabolites (e.g., Methotrexate, 5-Fluorouracil):** These interfere with DNA/RNA synthesis by acting as structural analogues of folic acid, purines, or pyrimidines. * **Mitotic Spindle Inhibitors (e.g., Vincristine, Paclitaxel):** These act on microtubules during the M-phase of the cell cycle, whereas alkylating agents are cell-cycle non-specific [2]. **High-Yield Clinical Pearls for NEET-PG:** * **Drug of Choice:** Temozolomide is the first-line treatment for **Glioblastoma Multiforme (GBM)** and Anaplastic Astrocytoma. * **Resistance:** Resistance to temozolomide is often mediated by the DNA repair enzyme **MGMT** (O6-methylguanine-DNA methyltransferase) [1]. Patients with a methylated (silenced) MGMT promoter respond better to the drug. * **Adverse Effects:** Significant myelosuppression (thrombocytopenia) and nausea. Prophylaxis against *Pneumocystis jirovecii* pneumonia (PJP) is often required when combined with radiotherapy.

Question 465: Which antineoplastic agent is an antifolate drug?

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

Explanation: **Explanation:** **1. Why Methotrexate is Correct:** Methotrexate is the prototypical **antifolate** antimetabolite. It acts by competitively and irreversibly inhibiting the enzyme **Dihydrofolate Reductase (DHFR)**. This inhibition prevents the conversion of dihydrofolate to tetrahydrofolate (the active form of folic acid), which is essential for the synthesis of thymidylate and purine nucleotides. Consequently, DNA synthesis, repair, and cellular replication are halted, specifically during the **S-phase** of the cell cycle. **2. Why the Other Options are Incorrect:** * **Adriamycin (Doxorubicin):** An **Anthracycline antibiotic** that works by intercalating between DNA base pairs, inhibiting Topoisomerase II, and generating free radicals. * **Vincristine:** A **Vinca alkaloid** that acts as a mitotic inhibitor. It binds to tubulin and prevents the polymerization of microtubules, leading to **M-phase** arrest. * **Cyclophosphamide:** An **Alkylating agent** (Nitrogen mustard) that forms cross-links within DNA strands, preventing DNA replication. It is a prodrug activated by hepatic CYP450. **Clinical Pearls for NEET-PG:** * **Rescue Therapy:** High-dose Methotrexate toxicity is managed with **Leucovorin (Folinic acid)**, which bypasses the blocked DHFR enzyme to provide a source of active folate. * **Adverse Effects:** Notable for causing mucositis, myelosuppression, and hepatotoxicity. Chronic use can lead to hepatic fibrosis. * **Antidote:** **Glucarpidase** can be used to rapidly lower extracellular methotrexate levels in patients with renal failure. * **Other Antifolates:** Pemetrexed (used in Mesothelioma) and Pralatrexate.

Question 466: All of the following are hormonal agents used against breast cancer EXCEPT:

A. Letrozole
B. Exemestane
C. Taxol (Correct Answer)
D. Tamoxifen

Explanation: **Explanation:** The correct answer is **Taxol (Paclitaxel)** because it is a **cytotoxic chemotherapy agent**, not a hormonal agent. 1. **Why Taxol is the correct answer:** Taxol belongs to the **Taxane** group of drugs. Its mechanism of action involves **stabilizing microtubules** (preventing depolymerization), which leads to mitotic arrest in the M-phase of the cell cycle. While it is a first-line treatment for breast cancer, it acts via cytotoxicity rather than hormonal modulation. 2. **Why the other options are incorrect (Hormonal Agents):** * **Tamoxifen:** A **Selective Estrogen Receptor Modulator (SERM)**. It acts as an antagonist on breast tissue receptors and is the gold standard for ER-positive breast cancer in pre-menopausal women. * **Letrozole:** A **Non-steroidal Aromatase Inhibitor (Type II)**. It reversibly inhibits the enzyme aromatase, preventing the peripheral conversion of androgens to estrogens. * **Exemestane:** A **Steroidal Aromatase Inhibitor (Type I)**. It binds irreversibly to aromatase ("suicide inhibition"). Both Letrozole and Exemestane are preferred for post-menopausal women. **High-Yield Clinical Pearls for NEET-PG:** * **Tamoxifen Side Effects:** Increased risk of **endometrial carcinoma** (due to agonist action on the uterus) and thromboembolism. * **Aromatase Inhibitors (AIs):** Unlike Tamoxifen, AIs do not increase the risk of uterine cancer but are associated with **osteoporosis** and bone fractures. * **Taxol Side Effects:** The dose-limiting toxicity is **peripheral neuropathy** and neutropenia. It is also known for causing hypersensitivity reactions (pre-medicate with steroids/antihistamines).

Question 467: Which of the following statements is true about imatinib?

A. It acts by inhibition of tyrosine kinase.
B. It is used to treat gastrointestinal stromal tumors (GIST).
C. A side effect of imatinib is pedal edema.
D. All of the above. (Correct Answer)

Explanation: **Explanation:** Imatinib is a revolutionary targeted therapy that belongs to the class of **Tyrosine Kinase Inhibitors (TKIs)**. It works by competitively binding to the ATP-binding site of specific tyrosine kinases, preventing the phosphorylation of substrates and subsequent cell signaling. * **Mechanism of Action (Option A):** Imatinib specifically inhibits the **BCR-ABL** tyrosine kinase (the product of the Philadelphia chromosome), as well as **c-KIT** (CD117) and **PDGFR** (Platelet-Derived Growth Factor Receptor). * **Clinical Utility (Option B):** Due to its inhibition of c-KIT, it is the first-line treatment for **Gastrointestinal Stromal Tumors (GIST)**. It is also the gold standard for **Chronic Myeloid Leukemia (CML)**. * **Side Effect Profile (Option C):** A hallmark side effect of imatinib is **fluid retention**, which most commonly manifests as **periorbital edema** and **pedal edema**. Other side effects include nausea, muscle cramps, and diarrhea. Since all three statements are pharmacologically accurate, **Option D** is the correct answer. **High-Yield Clinical Pearls for NEET-PG:** * **The "Magic Bullet":** Imatinib was the first drug designed to target a specific molecular abnormality (BCR-ABL). * **Resistance:** Resistance to imatinib often occurs due to mutations in the BCR-ABL kinase domain (e.g., **T315I mutation**). In such cases, second-generation TKIs like **Dasatinib** or **Nilotinib** are used. * **Monitoring:** Patients on imatinib should be monitored for cardiac function and fluid status.

Question 468: Methotrexate is an example for which of the following classes of drugs?

A. Antibiotic
B. Alkylating agent
C. Biologic response modifier
D. Folic acid analogue (Correct Answer)

Explanation: **Explanation:** **Methotrexate (MTX)** is a structural analogue of **folic acid**. It acts as an antimetabolite by competitively inhibiting the enzyme **Dihydrofolate Reductase (DHFR)**. This inhibition prevents the conversion of dihydrofolate to tetrahydrofolate (the active form of folic acid), which is essential for the synthesis of thymidylate and purine nucleotides. Consequently, DNA synthesis is halted, leading to cell death (S-phase specific). **Analysis of Options:** * **Option A (Antibiotic):** Anticancer antibiotics (e.g., Doxorubicin, Bleomycin) are derived from microorganisms and typically act by intercalating DNA or causing oxidative damage. * **Option B (Alkylating agent):** These drugs (e.g., Cyclophosphamide, Cisplatin) act by forming covalent bonds with DNA bases, leading to cross-linking and strand breaks. * **Option C (Biologic response modifier):** These agents (e.g., Interferon-alpha, Rituximab) modify the host's immune response to tumor cells rather than directly interfering with metabolic pathways. **High-Yield Clinical Pearls for NEET-PG:** 1. **Rescue Therapy:** **Leucovorin (Folinic acid)** is used as "Leucovorin Rescue" to bypass the DHFR block and protect normal cells from MTX toxicity. 2. **Adverse Effects:** The most common side effects include **mucositis**, bone marrow suppression, and **hepatotoxicity** (cirrhosis with long-term use). 3. **Resistance:** Resistance often occurs due to decreased drug uptake or an increase in DHFR enzyme levels within the cell. 4. **Non-Oncology Uses:** MTX is the first-line Disease-Modifying Antirheumatic Drug (**DMARD**) for Rheumatoid Arthritis and is also used in Psoriasis and Ectopic Pregnancy.

Question 469: Cyclophosphamide is used in all of the following conditions except?

A. Burkitt's lymphoma
B. Hodgkin's lymphoma
C. Choriocarcinoma (Correct Answer)
D. Ovarian carcinoma

Explanation: **Explanation:** **Cyclophosphamide** is a nitrogen mustard and a potent **alkylating agent**. It acts as a cell cycle non-specific drug by cross-linking DNA strands, primarily at the N7 position of guanine. **Why Choriocarcinoma is the correct answer:** The drug of choice for **Choriocarcinoma** is **Methotrexate** (an antimetabolite) or **Actinomycin D** (an antitumor antibiotic). Cyclophosphamide is not part of the standard primary treatment protocols (like EMA-CO) for gestational trophoblastic neoplasia. While it may be used in refractory cases, it is not a conventional or first-line indication compared to the other options listed. **Analysis of Incorrect Options:** * **Burkitt’s Lymphoma:** Cyclophosphamide is highly effective and is a cornerstone of treatment for this high-grade B-cell lymphoma. * **Hodgkin’s Lymphoma:** It is a key component of the **BEACOPP** regimen used in advanced stages of Hodgkin’s disease. * **Ovarian Carcinoma:** It is frequently used in combination with platinum compounds (like Cisplatin or Carboplatin) for the treatment of epithelial ovarian cancers. **High-Yield Clinical Pearls for NEET-PG:** 1. **Acrolein Toxicity:** Cyclophosphamide is a prodrug activated by CYP450. Its metabolite, **Acrolein**, causes **Hemorrhagic Cystitis**. 2. **Prevention:** Hemorrhagic cystitis is prevented by aggressive hydration and **MESNA** (2-Mercaptoethane sulfonate), which neutralizes acrolein in the bladder. 3. **Other Side Effects:** It is notorious for causing **SIADH** (dilutional hyponatremia) and permanent sterility (premature ovarian failure/azoospermia). 4. **Non-Oncology Use:** It is the drug of choice for **Wegener’s Granulomatosis** (Granulomatosis with polyangiitis).

Question 470: What is the drug of choice for Hairy cell leukemia?

A. Methotrexate
B. Gemcitabine
C. Cladribine (Correct Answer)
D. Decitabine

Explanation: **Explanation:** **Cladribine (2-CdA)** is the drug of choice for Hairy Cell Leukemia (HCL). It is a **purine nucleoside analog** that mimics adenosine. Its efficacy lies in its resistance to degradation by adenosine deaminase (ADA). Once inside the cell, it is phosphorylated into its active triphosphate form, which incorporates into DNA, leading to DNA strand breaks and apoptosis. Because HCL cells have high levels of deoxycytidine kinase and low levels of 5'-nucleotidase, the drug accumulates preferentially in these malignant cells, leading to high remission rates with a single continuous infusion. **Analysis of Incorrect Options:** * **A. Methotrexate:** A folate antagonist that inhibits dihydrofolate reductase (DHFR). It is primarily used in ALL, choriocarcinoma, and ectopic pregnancy, but is not effective for HCL. * **B. Gemcitabine:** A pyrimidine analog (cytidine analog) used mainly for solid tumors like pancreatic, lung, and bladder cancers. * **C. Decitabine:** A hypomethylating agent used in Myelodysplastic Syndrome (MDS) and AML, not HCL. **High-Yield Clinical Pearls for NEET-PG:** * **Pentostatin:** Another purine analog (ADA inhibitor) that is also highly effective for HCL but is generally considered second-line to Cladribine. * **BRAF V600E Mutation:** This is the hallmark genetic mutation found in nearly all cases of Hairy Cell Leukemia. * **Diagnosis:** Look for "dry tap" on bone marrow aspiration and "fried egg appearance" on biopsy. * **Alternative:** **Vemurafenib** (BRAF inhibitor) is used for relapsed/refractory cases.

Practice by Chapter

Principles of Cancer Chemotherapy

Practice Questions

Alkylating Agents

Practice Questions

Antimetabolites

Practice Questions

Antitumor Antibiotics

Practice Questions

Plant Alkaloids

Practice Questions

Topoisomerase Inhibitors

Practice Questions

Hormonal Agents

Practice Questions

Targeted Therapy

Practice Questions

Immunotherapy

Practice Questions

Management of Chemotherapy Side Effects

Practice Questions

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