Anticancer Drugs — MCQs

Anticancer Drugs Indian Medical PG Practice Questions and MCQs

Question 161: What adverse effect can be caused by cyclophosphamide?

A. Hemorrhagic cystitis (Correct Answer)
B. Hand-foot syndrome
C. Radiation recall
D. Cardiomyopathy

Explanation: **Explanation:** **Cyclophosphamide** is an alkylating agent (nitrogen mustard) [3] that acts as a prodrug. It is metabolized in the liver to form **Acrolein**, a toxic metabolite. Acrolein is excreted in the urine, where it causes direct irritation and sloughing of the bladder mucosa, leading to **Hemorrhagic Cystitis** (characterized by hematuria and dysuria) [3]. **Analysis of Options:** * **A. Hemorrhagic Cystitis (Correct):** This is the classic dose-limiting toxicity of cyclophosphamide [3]. It can be prevented by aggressive hydration and the administration of **MESNA** (2-Mercaptoethane sulfonate), which neutralizes acrolein in the bladder. * **B. Hand-foot syndrome:** This is primarily associated with **5-Fluorouracil (5-FU)** and its oral prodrug, **Capecitabine**. * **C. Radiation recall:** This phenomenon (skin reaction at a previous radiation site) is most commonly linked to **Dactinomycin (Actinomycin D)** and **Doxorubicin**. * **D. Cardiomyopathy:** This is the signature dose-dependent toxicity of Anthracyclines like **Doxorubicin** and **Daunorubicin**, caused by free radical generation. High-dose cyclophosphamide can also cause cardiac toxicity [2]. **High-Yield Clinical Pearls for NEET-PG:** 1. **SIADH:** Cyclophosphamide is also known to cause the Syndrome of Inappropriate Antidiuretic Hormone secretion. 2. **Mesna Mechanism:** Mesna contains a thiol group that binds to acrolein, forming a non-toxic adduct. 3. **Other Toxicities:** Long-term use of cyclophosphamide increases the risk of **Transitional Cell Carcinoma** of the bladder and infertility (premature ovarian failure/azoospermia). It is also known to cause myelosuppression [1].

Question 162: Tamoxifen is:

A. A non-steroidal antiprogesterone.
B. A non-steroidal antioestrogenic agent. (Correct Answer)
C. Synthetic progestogen norethindrone.
D. A competitive inhibitor of 5-alpha-reductase.

Explanation: **Explanation:** **Tamoxifen** is a **Selective Estrogen Receptor Modulator (SERM)**. It is a **non-steroidal** compound that acts as a competitive antagonist at estrogen receptors in the breast tissue, making it a mainstay in the treatment of estrogen receptor-positive (ER+) breast cancer. **Why Option B is Correct:** Tamoxifen binds to estrogen receptors (ER), preventing estrogen from binding. In breast tissue, it acts as an **antioestrogen**, inhibiting the growth of estrogen-dependent cancer cells. Because its chemical structure is not based on the four-ring cholesterol backbone, it is classified as **non-steroidal**. **Why Other Options are Incorrect:** * **Option A:** Tamoxifen does not target progesterone receptors; drugs like **Mifepristone** are antiprogesterones. * **Option C:** **Norethindrone** is a 19-nortestosterone derivative used in oral contraceptives, not a SERM. * **Option D:** **Finasteride** and **Dutasteride** are the competitive inhibitors of 5-alpha-reductase, used in BPH and male pattern baldness. **High-Yield Clinical Pearls for NEET-PG:** * **Dual Action:** While Tamoxifen is an antagonist in the breast, it acts as a **partial agonist** in the **endometrium** and **bone**. * **Side Effects:** Its agonist action on the uterus increases the risk of **endometrial carcinoma**. It also increases the risk of **thromboembolism** (DVT/PE). * **Benefits:** It helps prevent osteoporosis by maintaining bone mineral density (agonist effect on bone). * **Drug of Choice:** It is the DOC for breast cancer in **pre-menopausal** women (Aromatase inhibitors are preferred in post-menopausal women).

Question 163: Methotrexate blocks the synthesis of thymidine monophosphate by inhibiting the activity of which enzyme?

A. Dihydrofolate reductase (Correct Answer)
B. Orotate phosphoribosyl transferase
C. Ribonucleotide reductase
D. Dihydroorotase

Explanation: ### **Explanation** **Correct Option: A. Dihydrofolate Reductase (DHFR)** Methotrexate (MTX) is a folate antimetabolite. It acts as a structural analog of folic acid and binds to the active site of **Dihydrofolate Reductase (DHFR)** with an affinity 1,000 times greater than the natural substrate. * **Mechanism:** By inhibiting DHFR, MTX prevents the conversion of dihydrofolate (DHF) to tetrahydrofolate (THF). * **Result:** THF is a crucial co-factor for the enzyme **Thymidylate Synthase**, which converts dUMP to dTMP (Thymidine monophosphate). Depletion of THF leads to a "thymineless death" of the cell, halting DNA synthesis and repair. **Analysis of Incorrect Options:** * **B. Orotate phosphoribosyl transferase:** This enzyme is involved in the **de novo synthesis of pyrimidines** (converting orotic acid to OMP). It is inhibited by 5-Fluorouracil (5-FU) metabolites, not Methotrexate. * **C. Ribonucleotide reductase:** This enzyme converts ribonucleotides to deoxyribonucleotides. It is the primary target of **Hydroxyurea**. * **D. Dihydroorotase:** This is an early-stage enzyme in pyrimidine biosynthesis. It is not a major target for common clinical antineoplastic agents. --- ### **High-Yield Clinical Pearls for NEET-PG** * **Leucovorin Rescue:** Folinic acid (Leucovorin) is given to "bypass" the blocked DHFR enzyme in normal cells during high-dose MTX therapy, preventing lethal hematological toxicity. * **Resistance Mechanism:** The most common cause of MTX resistance is the **amplification of the DHFR gene** or mutations in the DHFR enzyme. * **Polyglutamation:** Inside the cell, MTX undergoes polyglutamation, which traps the drug inside the cell and increases its inhibitory potency. * **Toxicity:** Watch for **Mucositis** (earliest sign), Nephrotoxicity (due to crystalluria), and Hepatotoxicity (cirrhosis with long-term use in Psoriasis/RA).

Question 164: Which of the following drugs is not categorized under anti-VEGF agents?

A. Sunitinib
B. 5-Fluorouracil (Correct Answer)
C. Ranibizumab
D. Bevacizumab

Explanation: ### Explanation **Correct Answer: B. 5-Fluorouracil** **Why 5-Fluorouracil is the correct answer:** 5-Fluorouracil (5-FU) is an **Antimetabolite** (specifically a pyrimidine analog). Its primary mechanism of action is the inhibition of **thymidylate synthase**, which prevents the conversion of dUMP to dTMP. This leads to "thymineless death" of the cell by disrupting DNA synthesis. It does not directly target Vascular Endothelial Growth Factor (VEGF) or its receptors. **Analysis of Incorrect Options:** * **Bevacizumab:** A recombinant humanized **monoclonal antibody** that binds directly to circulating **VEGF-A** ligands, preventing them from binding to their receptors. It is widely used in colorectal and lung cancers. * **Ranibizumab:** A monoclonal antibody fragment (Fab) derived from bevacizumab. It is specifically designed for intravitreal injection to treat **neovascular (wet) Age-related Macular Degeneration (AMD)** by inhibiting VEGF. * **Sunitinib:** An oral **multi-targeted tyrosine kinase inhibitor (TKI)**. It inhibits the intracellular domain of **VEGFR-1, 2, and 3**, as well as PDGFR. It is a first-line agent for Renal Cell Carcinoma (RCC). **NEET-PG High-Yield Pearls:** 1. **VEGF Inhibitor Classification:** * **Antibodies (Ligand binders):** Bevacizumab, Ranibizumab, Aflibercept (VEGF Trap). * **Tyrosine Kinase Inhibitors (Receptor blockers):** Sunitinib, Sorafenib, Pazopanib. 2. **Side Effects of Anti-VEGFs:** Hypertension (most common), proteinuria, impaired wound healing, and arterial thrombosis. 3. **5-FU Toxicity:** Hand-foot syndrome (palmar-plantar erythrodysesthesia) and myelosuppression. Its action is enhanced by **Leucovorin** (folinic acid), which stabilizes the binding of 5-FU to thymidylate synthase.

Question 165: A 56-year-old female presented with breast carcinoma and was prescribed herceptin (trastuzumab). Which of the following statements regarding this drug is true?

A. It is an antibody produced entirely from mouse containing no human component.
B. It is a monoclonal antibody produced by injecting the HER2 antigen. (Correct Answer)
C. It is a polyclonal antibody.
D. It is a monoclonal antibody containing only a human component.

Explanation: **Explanation:** **Trastuzumab (Herceptin)** is a recombinant DNA-derived **monoclonal antibody (mAb)** specifically designed to target the **HER2/neu (ErbB2)** receptor, a tyrosine kinase receptor overexpressed in approximately 20-30% of breast cancers. 1. **Why Option B is Correct:** Monoclonal antibodies are produced by exposing an animal (typically a mouse) to a specific antigen—in this case, the **HER2 antigen**. B-cells from the animal are then fused with myeloma cells to create hybridomas that produce identical (monoclonal) antibodies targeting that specific epitope. 2. **Why Other Options are Incorrect:** * **Option A:** Trastuzumab is **humanized** (95% human, 5% murine). Purely murine antibodies end in the suffix *-omab*. * **Option C:** It is **monoclonal**, meaning it is derived from a single cell line and targets one specific epitope. Polyclonal antibodies are derived from multiple cell lines. * **Option D:** A "fully human" antibody (suffix *-umab*) contains 100% human components. Trastuzumab is "humanized" (suffix **-zumab**), meaning only the complementarity-determining regions (CDRs) are murine. **High-Yield Clinical Pearls for NEET-PG:** * **Mechanism:** It inhibits the proliferation of tumor cells that overexpress HER2 and mediates antibody-dependent cellular cytotoxicity (ADCC). * **Major Side Effect:** **Cardiotoxicity** (decreased LVEF/Heart Failure). Unlike anthracyclines (Doxorubicin), Trastuzumab-induced cardiotoxicity is usually **reversible** and not dose-dependent. * **Contraindication:** Avoid co-administration with anthracyclines due to synergistic cardiotoxicity. * **Nomenclature Tip:** * *-omab*: 100% Mouse * *-ximab*: Chimeric (65% Human) * *-zumab*: Humanized (95% Human) * *-umab*: 100% Human

Question 166: "Radiation recall syndrome" is seen with all of the following except?

A. Actinomycin
B. Bleomycin (Correct Answer)
C. Doxorubicin
D. Daunorubicin

Explanation: **Explanation:** **Radiation Recall Syndrome (RRS)** is an inflammatory skin reaction that occurs in a previously irradiated area after the administration of certain cytotoxic drugs. It represents a "latent" radiation injury triggered by chemotherapy, even months or years after radiotherapy. **Why Bleomycin is the correct answer:** While **Bleomycin** is notorious for causing pulmonary fibrosis and skin hyperpigmentation (flagellate dermatitis), it is **not** typically associated with Radiation Recall Syndrome. In contrast, the other options are classic triggers for this phenomenon. **Analysis of other options:** * **Actinomycin D (Dactinomycin):** This is the most common and potent inducer of radiation recall. It is frequently tested in exams as the classic cause. * **Doxorubicin & Daunorubicin:** These Anthracyclines are well-documented triggers for RRS. They are potent radiosensitizers and can cause severe inflammatory reactions in previously treated skin or internal organs (like the esophagus or lungs). **Clinical Pearls for NEET-PG:** * **Common Triggers:** The "Big Three" for RRS are **Actinomycin D, Anthracyclines (Doxorubicin), and Taxanes (Paclitaxel).** Other triggers include Methotrexate and Gemcitabine. * **Clinical Presentation:** It mimics a severe sunburn (erythema, edema, blistering) localized strictly to the previous radiation field. * **Management:** Treatment involves stopping the offending drug and administering corticosteroids. * **High-Yield Distinction:** Do not confuse *Radiation Recall* (occurs after radiation) with *Radiosensitization* (occurs when drug and radiation are given concurrently). Bleomycin is a radiosensitizer but not a recall agent.

Question 167: Imatinib acts on which of the following targets?

A. NMYC
B. Tyrosine kinase (Correct Answer)
C. PDGF
D. VEGF

Explanation: **Explanation:** **Imatinib** is a revolutionary targeted therapy that acts as a selective **Tyrosine Kinase Inhibitor (TKI)**. Its primary mechanism involves binding to the ATP-binding pocket of the **BCR-ABL** tyrosine kinase enzyme. This prevents the phosphorylation of substrates that lead to uncontrolled cell proliferation in Chronic Myeloid Leukemia (CML). * **Why Option B is Correct:** Imatinib specifically inhibits the BCR-ABL fusion protein (the product of the Philadelphia chromosome, t(9;22)). It also inhibits other tyrosine kinases, including **c-KIT** (mutated in Gastrointestinal Stromal Tumors - GIST) and **PDGFR** (Platelet-Derived Growth Factor Receptor). **Analysis of Incorrect Options:** * **Option A (NMYC):** This is a proto-oncogene often amplified in Neuroblastoma. It is a transcription factor, not a direct target for Imatinib. * **Option C (PDGF):** While Imatinib inhibits the *receptor* (PDGFR), it does not target the ligand (PDGF) itself. * **Option D (VEGF):** Vascular Endothelial Growth Factor is a target for drugs like Bevacizumab. Drugs targeting the VEGF *receptor* include Sorafenib and Sunitinib. **High-Yield Clinical Pearls for NEET-PG:** 1. **Drug of Choice (DOC):** Imatinib is the first-line treatment for **CML** and **GIST**. 2. **Resistance:** Resistance to Imatinib often occurs due to a point mutation in the BCR-ABL gene, most notably the **T315I mutation**. 3. **Adverse Effects:** The most characteristic side effect is **periorbital edema** (fluid retention). 4. **Metabolism:** It is metabolized by **CYP3A4**, making it prone to significant drug interactions.

Question 168: Which radiosensitizer drug is used in head and neck cancer treatment?

A. Paclitaxel (Correct Answer)
B. Cisplatin
C. Amikacin
D. Mitomycin-C

Explanation: **Explanation:** **1. Why Paclitaxel is Correct:** Paclitaxel belongs to the **Taxane** group of drugs, which act as **microtubule stabilizers**. They bind to the $\beta$-tubulin subunit, preventing depolymerization and freezing the cell in the **G2/M phase** of the cell cycle. The M (Mitotic) phase is the most radiosensitive phase of the cell cycle. By arresting a large population of tumor cells in this phase, Paclitaxel enhances the lethal effects of ionizing radiation, making it a potent **radiosensitizer** specifically used in the management of locally advanced head and neck squamous cell carcinomas (HNSCC). **2. Analysis of Incorrect Options:** * **Cisplatin:** While Cisplatin is frequently used concurrently with radiation in head and neck cancer (chemoradiotherapy), it is primarily classified as a **radiopotentiator** (inhibiting DNA repair) rather than a classic cell-cycle-specific radiosensitizer like Taxanes. In the context of standard NEET-PG patterns, Paclitaxel is the preferred answer for "radiosensitizer." * **Amikacin:** This is an Aminoglycoside antibiotic used for aerobic gram-negative infections. It has no role in oncology or radiosensitization. * **Mitomycin-C:** This is an alkylating agent used as a bioreductive drug. While it is used in anal canal and some head and neck cancers, it is specifically known as a **hypoxic cell sensitizer** (targeting cells in the center of the tumor with low oxygen), rather than a general radiosensitizer. **3. High-Yield Clinical Pearls for NEET-PG:** * **Radiosensitizers:** Drugs that increase the sensitivity of tumor cells to radiation (e.g., Paclitaxel, 5-Fluorouracil, Hydroxyurea). * **Radioprotectors:** Drugs that protect normal tissues from radiation damage (e.g., **Amifostine**, used to prevent xerostomia in head and neck radiation). * **Side Effect Note:** Paclitaxel is notorious for causing peripheral neuropathy and hypersensitivity reactions (pre-medicate with steroids and antihistamines).

Question 169: Which of the following is used in the treatment of urinary bladder carcinoma?

A. 5-Fluorouracil (5FU)
B. Bacillus Calmette-Guérin (BCG) (Correct Answer)
C. Cyclophosphamide
D. 6-Mercaptopurine

Explanation: **Explanation:** The correct answer is **Bacillus Calmette-Guérin (BCG)**. **Why BCG is correct:** BCG is a live-attenuated strain of *Mycobacterium bovis*. In oncology, it is the gold standard for **intravesical immunotherapy** in patients with non-muscle invasive bladder cancer (NMIBC), particularly high-grade tumors and Carcinoma in situ (CIS). When instilled into the bladder, BCG triggers a local inflammatory response and a robust T-cell mediated immune reaction (Th1 response). This immune activation leads to the destruction of malignant cells by cytotoxic T lymphocytes and natural killer (NK) cells. **Why the other options are incorrect:** * **5-Fluorouracil (5FU):** An antimetabolite (pyrimidine analog) primarily used for colorectal, breast, and head/neck cancers. While used topically for actinic keratosis, it is not a standard treatment for bladder carcinoma. * **Cyclophosphamide:** An alkylating agent used for various malignancies (lymphomas, leukemia). Paradoxically, it is a **risk factor** for bladder cancer because its metabolite, **Acrolein**, causes hemorrhagic cystitis and chronic urothelial irritation. * **6-Mercaptopurine:** A purine analog used mainly in the maintenance therapy of Acute Lymphoblastic Leukemia (ALL). It has no role in bladder cancer management. **High-Yield Clinical Pearls for NEET-PG:** * **Acrolein Toxicity:** To prevent hemorrhagic cystitis caused by Cyclophosphamide, patients are given **MESNA** (2-Mercaptoethane sulfonate Na) and aggressive hydration. * **BCG Contraindications:** It should not be used in patients with gross hematuria, traumatic catheterization, or immunosuppression due to the risk of systemic BCG-osis (sepsis). * **Other Intravesical Agents:** If BCG fails or is unavailable, **Mitomycin C** or **Gemcitabine** are alternative intravesical chemotherapeutic agents used for bladder cancer.

Question 170: Which one of the following drugs is a Topoisomerase 1 inhibitor?

A. Doxorubicin
B. Irinotecan (Correct Answer)
C. Etoposide
D. Vincristine

Explanation: **Explanation:** The correct answer is **Irinotecan**. **1. Mechanism of Action (Topoisomerase I Inhibitors):** Topoisomerase I is an enzyme responsible for creating single-strand breaks in DNA to relieve torsional strain during replication. Drugs like **Irinotecan** and **Topotecan** (derivatives of Camptothecin) bind to the DNA-topoisomerase I complex, preventing the religation of these single-strand breaks. This leads to lethal double-strand DNA damage and cell death. **2. Analysis of Incorrect Options:** * **Doxorubicin:** An anthracycline antibiotic that inhibits **Topoisomerase II**, intercalates DNA, and generates free radicals. * **Etoposide:** A podophyllotoxin derivative that specifically inhibits **Topoisomerase II**, leading to double-strand DNA breaks. * **Vincristine:** A Vinca alkaloid that inhibits **microtubule polymerization** by binding to tubulin, causing mitotic arrest in the M-phase. **3. High-Yield Clinical Pearls for NEET-PG:** * **Irinotecan Side Effects:** Known for causing severe **diarrhea**. * *Early-onset:* Occurs within 24 hours (cholinergic crisis); treated with **Atropine**. * *Late-onset:* Occurs after 24 hours; treated with **Loperamide**. * **Pharmacogenomics:** Patients with **UGT1A1*28 polymorphism** (Gilbert syndrome) are at a higher risk of severe toxicity from Irinotecan due to impaired glucuronidation of its active metabolite, SN-38. * **Mnemonic:** Remember **"I"** for **I**rinotecan and Topoisomerase **I**. Remember **"E"**toposide and **"D"**oxorubicin for Topoisomerase **II** (Two).

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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