Anticancer Drugs Practice Questions

Q: Hand and foot syndrome can be caused by which of the following agents?

Capecitabine. **Explanation:** **Hand-Foot Syndrome (HFS)**, also known as **Palmar-Plantar Erythrodysesthesia**, is a distinct dermatological toxicity characterized by redness, swelling, and pain on the palms and soles. 1. **Why Capecitabine is correct:** Capecitabine is an oral prodrug of **5-Fluorouracil (5-FU)**. It is the most common agent associated with HFS. The underlying mechanism involves the high levels of the enzyme **thymidine phosphorylase** in the skin of palms and soles, which converts the prodrug into active 5-FU, leading to localized cytotoxic damage. Other drugs frequently causing HFS include **5-FU (infusion)** and **Liposomal Doxorubicin**. 2. **Why other options are incorrect:** * **Cisplatin:** Primarily known for **nephrotoxicity** (prevented by amifostine/hydration) and **ototoxicity**. * **Vincristine:** Characterized by **peripheral neuropathy** (stocking-glove pattern) and autonomic dysfunction (constipation/paralytic ileus). It is notably bone marrow sparing. * **Mitomycin-C:** Associated with **Delayed Myelosuppression** and **Hemolytic Uremic Syndrome (HUS)**. **High-Yield Clinical Pearls for NEET-PG:** * **Management of HFS:** Dose reduction/interruption and topical emollients (Urea cream) or Pyridoxine (Vitamin B6). * **Hand-Foot Skin Reaction (HFSR):** Distinct from HFS; it presents with hyperkeratosis/calluses and is caused by **Tyrosine Kinase Inhibitors (TKIs)** like **Sorafenib** and **Sunitinib**. * **5-FU Toxicity:** Deficiency of the enzyme **DPD (Dihydropyrimidine dehydrogenase)** increases the risk of severe toxicity.

Q: Pemetrexed, a drug useful in breast cancer, belongs to which of the following categories?

Antimetabolite. **Explanation:** **Pemetrexed** is a multi-targeted **antimetabolite** (Option D). Antimetabolites are cell-cycle specific drugs that act primarily during the **S-phase** by interfering with DNA and RNA synthesis. Pemetrexed works by inhibiting three key enzymes involved in folate metabolism: 1. **Thymidylate synthase (TS)** 2. **Dihydrofolate reductase (DHFR)** 3. **Glycinamide ribonucleotide formyltransferase (GARFT)** By inhibiting these enzymes, it prevents the formation of precursor purine and pyrimidine nucleotides, thereby halting DNA synthesis and inducing apoptosis in cancer cells. **Why other options are incorrect:** * **A. Antitumor agents (Antibiotics):** These are derived from microorganisms (e.g., Doxorubicin, Bleomycin) and typically act by intercalating DNA or causing strand breaks, not by mimicking metabolites. * **B. Alkylating agents:** These drugs (e.g., Cyclophosphamide, Cisplatin) work by forming covalent bonds with DNA, leading to cross-linking and strand breakage. They are cell-cycle non-specific. * **C. Hormonal agents:** These include Tamoxifen or Anastrozole, which modulate hormone receptors or synthesis in hormone-dependent cancers. **High-Yield Clinical Pearls for NEET-PG:** * **Indications:** Primarily used in **Malignant Pleural Mesothelioma** (in combination with Cisplatin) and **Non-Small Cell Lung Cancer (NSCLC)**. * **Toxicity Management:** To reduce hematologic and GI toxicity, patients must be pre-treated with **Vitamin B12 and Folic Acid** supplementation. * **Skin Reactions:** Dexamethasone is often co-administered to prevent pemetrexed-induced cutaneous rashes.

Q: Which of the following anticancer drugs is excreted by the lungs?

5-Fluorouracil. **Explanation:** **Correct Answer: A. 5-Fluorouracil (5-FU)** 5-Fluorouracil is a pyrimidine analog that undergoes extensive hepatic metabolism. The rate-limiting enzyme, **dihydropyrimidine dehydrogenase (DPD)**, converts 5-FU into dihydrofluorouracil [1]. Ultimately, it is broken down into **carbon dioxide (CO₂)**, urea, and α-fluoro-β-alanine. The CO₂ produced during this metabolic degradation is primarily **excreted through the lungs**. This unique pharmacokinetic property is the basis for the "13C-FU breath test" used to assess DPD activity in patients. **Analysis of Incorrect Options:** * **B. Cyclophosphamide:** This alkylating agent is a prodrug activated by hepatic CYP450 enzymes. Its metabolites, including the toxic byproduct **acrolein** (which causes hemorrhagic cystitis), are primarily excreted via the **kidneys**. * **C. Doxorubicin:** This anthracycline antibiotic is metabolized by the liver and is predominantly excreted via the **biliary system** (feces). Dose adjustment is required in patients with hepatic dysfunction. * **D. Cisplatin:** This platinum compound is cleared almost exclusively by the **kidneys** through glomerular filtration and tubular secretion [2]. It is notorious for causing nephrotoxicity. **High-Yield Clinical Pearls for NEET-PG:** * **DPD Deficiency:** Patients with a genetic deficiency of dihydropyrimidine dehydrogenase (DPD) are at high risk for severe, life-threatening toxicity (mucositis, myelosuppression) when given 5-FU. * **Hand-Foot Syndrome:** A common dermatological side effect associated with 5-FU and its oral prodrug, Capecitabine. * **Rescue Agent:** **Uridine triacetate** is the specific antidote for 5-FU overdose or toxicity.

Q: The figure shows the mechanism of action of which of the following drugs?

Nilotinib. ***Nilotinib*** - **Second-generation tyrosine kinase inhibitor** that specifically targets **BCR-ABL** fusion protein in chronic myeloid leukemia (CML). - Binds to the **ATP-binding site** of BCR-ABL kinase, blocking its autophosphorylation and downstream signaling pathways that promote cell proliferation. *Methotrexate* - Acts as a **dihydrofolate reductase (DHFR) inhibitor**, preventing conversion of dihydrofolate to tetrahydrofolate. - Mechanism involves **folate antagonism**, not tyrosine kinase inhibition, disrupting **DNA synthesis** and **purine metabolism**. *Pertuzumab* - **Monoclonal antibody** that binds to **HER2 receptor**, preventing **heterodimerization** with other HER family receptors. - Mechanism involves **receptor blockade** rather than kinase inhibition, primarily used in **HER2-positive breast cancer**. *Cisplatin* - **Platinum-based alkylating agent** that forms **DNA cross-links** between and within DNA strands. - Mechanism involves **DNA damage** and **apoptosis induction**, not kinase pathway interference like tyrosine kinase inhibitors.

Q: Which of the following antineoplastic drugs causes hepatotoxicity?

6-mercaptopurine. **Explanation:** **6-Mercaptopurine (6-MP)** is a thiopurine antimetabolite that acts as a purine analogue. It is a well-known cause of **hepatotoxicity**, which typically manifests as cholestatic jaundice, elevated transaminases, or even hepatic necrosis. The toxicity is often dose-related and is linked to its metabolism by the enzyme **Thiopurine Methyltransferase (TPMT)**. Patients with genetic deficiencies in TPMT are at a significantly higher risk of severe bone marrow suppression and hepatotoxicity when treated with standard doses of 6-MP or its prodrug, Azathioprine. **Analysis of Incorrect Options:** * **5-Fluorouracil (5-FU):** Primarily associated with gastrointestinal toxicity (mucositis, diarrhea) and **Hand-Foot Syndrome** (palmar-plantar erythrodysesthesia). It is not typically associated with significant hepatotoxicity. * **Doxorubicin:** An anthracycline antibiotic famous for its **cardiotoxicity** (dilated cardiomyopathy) due to free radical generation. Its main dose-limiting toxicity is myelosuppression. * **Etoposide:** A topoisomerase II inhibitor. Its primary adverse effects are myelosuppression and alopecia; it is also associated with a risk of secondary leukemia. **High-Yield NEET-PG Pearls:** * **TPMT Testing:** Always screen for TPMT activity before starting 6-MP to prevent life-threatening toxicity. * **Drug Interaction:** **Allopurinol** inhibits Xanthine Oxidase (the enzyme that degrades 6-MP). Co-administration leads to toxic levels of 6-MP; therefore, the dose of 6-MP must be reduced by 50-75%. * **Other Hepatotoxic Chemo Agents:** Methotrexate (cirrhosis/fibrosis), L-asparaginase, and Busulfan (Veno-occlusive disease).

Q: Stocking and glove neuropathy is seen in which of the following chemotherapeutic agents?

Paclitaxel. **Explanation:** **Correct Option: B (Paclitaxel)** Paclitaxel, a taxane, acts by stabilizing microtubules and preventing their disassembly (arresting cells in the M-phase). Its most characteristic dose-limiting toxicity is **peripheral neuropathy**, typically presenting in a **"stocking and glove" distribution**. This occurs because taxanes interfere with microtubule-dependent axonal transport, leading to distal axonal degeneration. Sensory symptoms (numbness, tingling, and burning pain) usually precede motor involvement. **Analysis of Incorrect Options:** * **A. Vinblastine:** While Vinca alkaloids (like Vincristine) are notorious for neurotoxicity, Vinblastine is primarily associated with **bone marrow suppression** (Vin**b**lastine **b**lasts the **b**one marrow). Vincristine is more commonly linked to peripheral neuropathy than Vinblastine. * **C. Etoposide:** This is a Topoisomerase II inhibitor. Its major side effects are myelosuppression and alopecia. It is also associated with an increased risk of secondary leukemia. * **D. Mitoxantrone:** An anthracenedione used in prostate cancer and MS. Its primary concern is **cardiotoxicity** (though less than Doxorubicin) and it can cause a harmless blue-green discoloration of urine and sclera. **High-Yield Clinical Pearls for NEET-PG:** * **Microtubule Inhibitors:** Remember "Vincas prevent assembly, Taxanes prevent disassembly." * **Other drugs causing Peripheral Neuropathy:** Vincristine, Cisplatin, Oxaliplatin (cold-induced), Thalidomide, and Bortezomib. * **Paclitaxel Pre-medication:** To prevent hypersensitivity reactions (due to the Cremophor EL vehicle), patients are pre-treated with Dexamethasone, H1 blockers, and H2 blockers.

Q: Which of the following immunosuppressive agents acts primarily by inhibiting helper T cells?

Cyclosporine. **Explanation:** **Correct Answer: A. Cyclosporine** Cyclosporine is a potent immunosuppressant classified as a **Calcineurin Inhibitor**. Its primary mechanism involves binding to the intracellular protein **Cyclophilin**. This complex inhibits Calcineurin, a phosphatase required for the dephosphorylation and activation of the **Nuclear Factor of Activated T-cells (NFAT)**. Consequently, the transcription of **Interleukin-2 (IL-2)** is blocked. Since IL-2 is the primary cytokine responsible for the proliferation and activation of **Helper T-cells (CD4+ cells)**, Cyclosporine effectively suppresses T-cell-mediated immunity. **Analysis of Incorrect Options:** * **B. Azathioprine:** This is a purine antimetabolite (prodrug of 6-Mercaptopurine). It inhibits DNA synthesis, affecting the proliferation of both T and B lymphocytes non-specifically, rather than acting primarily as a signaling inhibitor in helper T-cells. * **C. Cytarabine:** An antimetabolite (Pyrimidine analog) used primarily in chemotherapy for Acute Myeloid Leukemia (AML). It inhibits DNA polymerase and is not used as a primary immunosuppressant for T-cell inhibition. * **D. Cycloserine:** An antitubercular drug (second-line) that inhibits bacterial cell wall synthesis by acting as an analog of D-alanine. It has no role in immunosuppression. **High-Yield Clinical Pearls for NEET-PG:** * **Side Effects of Cyclosporine:** Remember the "5 H's"—**H**irsutism, **H**yperplasia of gums (gingival hypertrophy), **H**ypertension, **H**yperlipidemia, and **H**epatotoxicity. It is also notably **Nephrotoxic**. * **Drug Interactions:** Cyclosporine is metabolized by **CYP3A4**; its levels increase with Grapefruit juice and Macrolides. * **Comparison:** Unlike Cyclosporine, **Tacrolimus** binds to **FKBP-12** but shares the same mechanism of inhibiting Calcineurin. Tacrolimus does *not* cause hirsutism or gingival hyperplasia.

Q: Which antimetabolite antineoplastic agent is used in the treatment of mesothelioma?

Pemetrexed. **Explanation:** **Pemetrexed** is the correct answer. It is a multi-targeted antifolate antimetabolite that inhibits three key enzymes in folate metabolism: **thymidylate synthase (TS)**, **dihydrofolate reductase (DHFR)**, and **glycinamide ribonucleotide formyltransferase (GARFT)**. Its primary clinical indication is in the treatment of **malignant pleural mesothelioma** (in combination with Cisplatin) and non-small cell lung cancer (NSCLC). **Analysis of Incorrect Options:** * **A. 6-thioguanine:** A purine analog used primarily in the treatment of acute leukemias (AML). It does not have a role in solid tumors like mesothelioma. * **B. 5-FU (5-Fluorouracil):** A pyrimidine analog used extensively for GI tract cancers (colorectal, gastric) and breast cancer, but it is not the standard of care for mesothelioma. * **C. Busulfan:** An **alkylating agent** (specifically an alkyl sulfonate), not an antimetabolite. It is primarily used in chronic myeloid leukemia (CML) and as a conditioning agent before bone marrow transplantation. **High-Yield Clinical Pearls for NEET-PG:** * **Supplementation:** To reduce the hematologic and GI toxicity of Pemetrexed, patients must be pre-treated with **Vitamin B12 and Folic Acid**. * **Skin Reactions:** Dexamethasone is often given to prevent the cutaneous rash associated with Pemetrexed. * **Mechanism:** Unlike Methotrexate (which primarily inhibits DHFR), Pemetrexed’s inhibition of TS and GARFT makes it more effective against a broader range of solid tumors. * **Drug of Choice:** Pemetrexed + Cisplatin is the first-line chemotherapy regimen for unresectable mesothelioma.

Q: Coasting effect is seen with which of the following agents?

Platinum compounds. **Explanation:** The **"Coasting Effect"** refers to a unique clinical phenomenon where neurotoxicity (specifically peripheral sensory neuropathy) continues to progress or worsen for several weeks to months even after the offending drug has been discontinued. **1. Why Platinum Compounds are correct:** Platinum-based agents, most notably **Oxaliplatin** (and to a lesser extent Cisplatin), are the classic cause of the coasting effect. These drugs accumulate in the dorsal root ganglia. Due to their slow clearance from neuronal tissues, DNA damage and oxidative stress continue to evolve even after plasma levels drop. Patients may report worsening numbness, tingling, or pain long after their final chemotherapy cycle. **2. Why the other options are incorrect:** * **Nitrogen mustards (e.g., Cyclophosphamide):** Their primary dose-limiting toxicity is myelosuppression and hemorrhagic cystitis. While they can cause some neurotoxicity (Ifosfamide), they do not typically exhibit the coasting phenomenon. * **Methotrexate:** Known for myelosuppression, mucositis, and hepatotoxicity. While intrathecal use can cause leucoencephalopathy, it does not cause the delayed sensory "coasting" seen with platinums. * **Dacarbazine:** Primarily causes severe nausea/vomiting and myelosuppression. It is not associated with progressive delayed neuropathy. **High-Yield Clinical Pearls for NEET-PG:** * **Oxaliplatin:** Distinctive for **cold-induced dysesthesia** (exacerbated by cold drinks/weather). * **Cisplatin:** Notable for **ototoxicity** (high-frequency hearing loss) and **nephrotoxicity** (prevented by aggressive hydration and Amifostine). * **Vinca Alkaloids (Vincristine):** Also cause peripheral neuropathy, but unlike platinums, the symptoms usually stabilize or improve relatively quickly upon discontinuation rather than "coasting."

Q: Which of the following anticancer drugs is least likely to cause nausea and vomiting?

Chlorambucil. **Explanation:** The emetogenic potential of chemotherapy is a high-yield topic for NEET-PG. Anticancer drugs are classified into four categories based on their risk of causing nausea and vomiting: High (>90%), Moderate (30–90%), Low (10–30%), and Minimal (<10%). **1. Why Chlorambucil is correct:** Chlorambucil is an oral alkylating agent (nitrogen mustard) used primarily in Chronic Lymphocytic Leukemia (CLL). It is classified as having **minimal emetogenic potential** ( 90% risk). It triggers both acute and delayed emesis by releasing serotonin from enterochromaffin cells and acting on the Chemoreceptor Trigger Zone (CTZ). * **Doxorubicin & Daunorubicin (Options C & D):** These anthracyclines are classified as having **moderate emetogenic potential** (30–90% risk). When combined with cyclophosphamide (AC regimen), they are treated as highly emetogenic. **NEET-PG High-Yield Pearls:** * **Highest Emetogenic Potential:** Cisplatin (most common answer), Dacarbazine, and high-dose Cyclophosphamide. * **Drug of Choice for Cisplatin-induced vomiting:** 5-HT3 antagonists (e.g., Ondansetron) are used for acute emesis; NK1 receptor antagonists (e.g., Aprepitant) are added for delayed emesis. * **Least Emetogenic Agents:** Vincristine, Bleomycin, Busulfan, and Chlorambucil. * **Anticipatory Vomiting:** Best managed with Benzodiazepines (e.g., Lorazepam).

Question 1

Hand and foot syndrome can be caused by which of the following agents?

Accepted Answer

Capecitabine

Answer

Cisplatin

Answer

Vincristine

Answer

Mitomycin-C

Question 2

Pemetrexed, a drug useful in breast cancer, belongs to which of the following categories?

Accepted Answer

Antimetabolite

Answer

Antitumor agent

Answer

Alkylating agent

Answer

Hormonal agent

Question 3

Which of the following anticancer drugs is excreted by the lungs?

Accepted Answer

5-Fluorouracil

Answer

Cyclophosphamide

Answer

Doxorubicin

Answer

Cisplatin

Question 4

The figure shows the mechanism of action of which of the following drugs?

Accepted Answer

Nilotinib

Answer

Methotrexate

Answer

Pertuzumab

Answer

Cisplatin

Question 5

Which of the following antineoplastic drugs causes hepatotoxicity?

Accepted Answer

6-mercaptopurine

Answer

5-fluorouracil

Answer

Doxorubicin

Answer

Etoposide

Question 6

Stocking and glove neuropathy is seen in which of the following chemotherapeutic agents?

Accepted Answer

Paclitaxel

Answer

Vinblastine

Answer

Etoposide

Answer

Mitoxantrone

Question 7

Which of the following immunosuppressive agents acts primarily by inhibiting helper T cells?

Accepted Answer

Cyclosporine

Answer

Azathioprine

Answer

Cytarabine

Answer

Cycloserine

Question 8

Which antimetabolite antineoplastic agent is used in the treatment of mesothelioma?

Accepted Answer

Pemetrexed

Answer

6-thioguanine

Answer

5-FU

Answer

Busulfan

Question 9

Coasting effect is seen with which of the following agents?

Accepted Answer

Platinum compounds

Answer

Nitrogen mustards

Answer

Methotrexate

Answer

Dacarbazine

Question 10

Which of the following anticancer drugs is least likely to cause nausea and vomiting?

Accepted Answer

Chlorambucil

Answer

Cisplatin

Answer

Doxorubicin

Answer

Daunorubicin

Anticancer Drugs — MCQs

Anticancer Drugs — MCQs

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