Anticancer Drugs — MCQs

Anticancer Drugs Indian Medical PG Practice Questions and MCQs

Question 401: Pentostatin acts by inhibiting which enzyme?

A. RNA dependent DNA polymerase
B. Aldolase
C. Adenosine deaminase (Correct Answer)
D. Adenylyl cyclase

Explanation: **Explanation:** **Pentostatin** (2'-deoxycoformycin) is a potent transition-state analog inhibitor of the enzyme **Adenosine Deaminase (ADA)**. **Mechanism of Action:** ADA is a critical enzyme in the purine salvage pathway that converts adenosine to inosine and deoxyadenosine to deoxyinosine. By inhibiting ADA, Pentostatin leads to an intracellular accumulation of **deoxyadenosine triphosphate (dATP)**. High levels of dATP are toxic to lymphocytes because they inhibit ribonucleotide reductase, thereby depleting the deoxynucleotide pools required for DNA synthesis and repair. This leads to apoptosis, particularly in T and B cells. **Analysis of Incorrect Options:** * **A. RNA-dependent DNA polymerase:** Also known as Reverse Transcriptase, this is the target for antiretroviral drugs (like Zidovudine) used in HIV treatment, not Pentostatin. * **B. Aldolase:** This is a glycolytic enzyme. While some experimental drugs target metabolic pathways, it is not the target for any standard anticancer purine analog. * **D. Adenylyl cyclase:** This enzyme converts ATP to cyclic AMP (cAMP) and is involved in G-protein coupled receptor signaling. It is not a target for cytotoxic chemotherapy. **High-Yield Clinical Pearls for NEET-PG:** * **Drug of Choice:** Pentostatin is highly effective and considered a primary treatment for **Hairy Cell Leukemia**. * **Toxicity:** The major dose-limiting toxicities are myelosuppression and nephrotoxicity. * **ADA Deficiency:** Congenital deficiency of Adenosine Deaminase leads to **Severe Combined Immunodeficiency (SCID)**, highlighting the enzyme's vital role in lymphocyte survival. * **Related Drug:** **Cladribine** is another purine analog used for Hairy Cell Leukemia; it is resistant to degradation by ADA.

Question 402: Thalidomide, used for multiple myeloma, is:

A. Associated with diarrhea
B. Characterized by enantiomeric interconversions (Correct Answer)
C. Metabolized extensively by hepatic CYP system
D. Safe for use in pregnant females

Explanation: **Explanation:** **1. Why Option B is Correct:** Thalidomide exists as a racemic mixture of two enantiomers: the **(R)-enantiomer**, which provides the desired sedative and immunomodulatory effects, and the **(S)-enantiomer**, which is highly teratogenic. A critical pharmacological property of thalidomide is that these enantiomers undergo **spontaneous interconversion (*in vivo* racemization)** under physiological pH. Therefore, even if a pure (R)-enantiomer is administered, it will convert into the toxic (S)-form within the body, making it impossible to eliminate the risk of teratogenicity through purification. **2. Why Other Options are Incorrect:** * **Option A:** Thalidomide is more commonly associated with **constipation**, not diarrhea. It also causes peripheral neuropathy and sedation. * **Option C:** Unlike many drugs, thalidomide is **not extensively metabolized by the hepatic CYP450 system**. It undergoes non-enzymatic spontaneous hydrolysis in the plasma. This makes it relatively safe to use in patients with liver dysfunction. * **Option D:** Thalidomide is a notorious **teratogen (Category X)**. It causes **Phocomelia** (seal-like limbs) by inhibiting angiogenesis via the suppression of TNF-α and basic fibroblast growth factor (bFGF). It is strictly contraindicated in pregnancy. **3. NEET-PG High-Yield Pearls:** * **Mechanism in Myeloma:** It inhibits TNF-α, reduces IL-6, and has anti-angiogenic properties. * **The "STEPS" Program:** Due to its teratogenicity, it is prescribed under a restricted distribution program. * **Analogs:** **Lenalidomide** is a more potent analog used in Multiple Myeloma and 5q-minus Myelodysplastic Syndrome; it is less sedative but causes more bone marrow suppression. * **Other Uses:** Erythema Nodosum Leprosum (ENL) and Aphthous ulcers in HIV.

Question 403: Which anticancer drug inhibits dihydrofolate reductase?

A. Vincristine
B. Methotrexate (Correct Answer)
C. Paclitaxel
D. Cisplatin

Explanation: **Explanation:** **Methotrexate (MTX)** is the correct answer because it is a folate antagonist that acts as a competitive inhibitor of the enzyme **dihydrofolate reductase (DHFR)**. This enzyme is responsible for converting dihydrofolate into tetrahydrofolate (THF). THF is a critical co-factor required for the synthesis of thymidylate and purine nucleotides. By inhibiting DHFR, Methotrexate halts DNA synthesis and repair, making it an S-phase specific antimetabolite. **Analysis of Incorrect Options:** * **Vincristine:** A Vinca alkaloid that acts by binding to tubulin and inhibiting **microtubule polymerization**, leading to mitotic arrest in the M-phase. * **Paclitaxel:** A Taxane that works by **stabilizing microtubules** (inhibiting depolymerization), preventing the breakdown of the mitotic spindle during the M-phase. * **Cisplatin:** A platinum compound that acts as an **alkylating-like agent**. It forms intra-strand and inter-strand cross-links with DNA, leading to DNA damage and apoptosis. **High-Yield Clinical Pearls for NEET-PG:** * **Rescue Therapy:** To prevent systemic toxicity (bone marrow suppression/mucositis), **Leucovorin (folinic acid)** is administered. It bypasses the blocked DHFR enzyme to provide a source of reduced folate. * **Resistance:** Most commonly occurs due to decreased drug uptake, decreased polyglutamation, or **amplification/mutation of the DHFR gene**. * **Adverse Effects:** Nephrotoxicity (prevented by hydration and urinary alkalinization), hepatotoxicity (cirrhosis with long-term use), and pulmonary fibrosis. * **Other DHFR Inhibitors:** Pyrimethamine (Antiprotozoal) and Trimethoprim (Antibacterial).

Question 404: Which of the following is NOT used in the management of carcinoma of the prostate?

A. Estrogen
B. Progesterone (Correct Answer)
C. Cyproterone acetate
D. Flutamide

Explanation: Carcinoma of the prostate is an androgen-dependent tumor. Therefore, the primary goal of pharmacological management is **Androgen Deprivation Therapy (ADT)**, achieved by either reducing testosterone production or blocking androgen receptors. ### **Explanation of Options:** * **Progesterone (Correct Answer):** While progestins are used in endometrial and breast cancers, they have no established therapeutic role in the management of prostate cancer. They do not effectively suppress the hypothalamic-pituitary-gonadal axis or block androgen receptors in a clinically significant way for this malignancy. * **Estrogens (Option A):** Historically, high-dose estrogens (e.g., Diethylstilbestrol) were used to treat prostate cancer. They act via negative feedback on the pituitary to decrease LH secretion, thereby reducing testicular testosterone production. However, their use has declined due to cardiovascular side effects. * **Cyproterone Acetate (Option C):** This is a steroidal anti-androgen with dual action: it blocks androgen receptors and has progestational activity that suppresses LH secretion. * **Flutamide (Option D):** This is a non-steroidal (pure) anti-androgen that competitively inhibits androgen receptors in the prostate tissue. It is frequently used alongside GnRH agonists to prevent the "testosterone flare." ### **High-Yield Clinical Pearls for NEET-PG:** * **DOC for Metastatic Prostate Cancer:** GnRH agonists (e.g., **Leuprolide**, Goserelin) or GnRH antagonists (e.g., **Degarelix**). * **Abiraterone:** A CYP17 inhibitor that blocks androgen synthesis in the testes, adrenals, and the tumor itself. * **Enzalutamide:** A potent, next-generation androgen receptor signaling inhibitor. * **Bicalutamide:** Preferred over Flutamide due to a better safety profile (less hepatotoxicity) and once-daily dosing.

Question 405: In the VAPD regimen used in the management of ALL, which of the following drugs is not included?

A. Vincristine
B. Prednisolone
C. Idarubicin (Correct Answer)
D. Doxorubicin

Explanation: The **VAPD regimen** is a standard induction chemotherapy protocol used in the management of **Acute Lymphoblastic Leukemia (ALL)**. The acronym stands for: * **V:** Vincristine * **A:** Adriamycin (Doxorubicin) * **P:** Prednisolone * **D:** L-asparaginase (or sometimes Daunorubicin) ### Why Idarubicin is the Correct Answer **Idarubicin** is an anthracycline primarily used in the treatment of **Acute Myeloid Leukemia (AML)** rather than ALL. While it is structurally related to Doxorubicin, it is not a component of the classic VAPD induction regimen for pediatric or adult ALL. ### Explanation of Incorrect Options * **Vincristine (Option A):** A vinca alkaloid that inhibits microtubule polymerization. It is a backbone of almost all ALL regimens due to its lack of bone marrow toxicity. * **Prednisolone (Option B):** A glucocorticoid that induces apoptosis in lymphoid cells. It is essential for the initial "lymphoblast clear-out." * **Doxorubicin (Option C):** Also known as Adriamycin, this anthracycline inhibits Topoisomerase II. It represents the "A" in VAPD (though Daunorubicin is often substituted, both are part of the protocol logic). ### High-Yield Clinical Pearls for NEET-PG 1. **Vincristine Side Effect:** Distinctive for **peripheral neuropathy** (foot drop, constipation/paralytic ileus) but is **bone marrow sparing**. 2. **L-asparaginase:** Often the "D" in VAPD (referring to the drug's action or specific protocols like VAPL). Its unique side effects include **acute pancreatitis** and **hypofibrinogenemia**. 3. **Anthracycline Toxicity:** Both Doxorubicin and Daunorubicin cause **dilated cardiomyopathy** (dose-dependent). **Dexrazoxane** is used to prevent this cardiotoxicity. 4. **Tumor Lysis Syndrome (TLS):** Always monitor for hyperuricemia and hyperkalemia when starting VAPD in ALL patients with high tumor burden.

Question 406: All are indications of methotrexate except?

A. Leukemia
B. Breast cancer
C. Rheumatoid arthritis
D. Renal failure (Correct Answer)

Explanation: **Explanation:** **Methotrexate (MTX)** is a folate antagonist that inhibits the enzyme **dihydrofolate reductase (DHFR)**, leading to a decrease in tetrahydrofolate levels and subsequent inhibition of DNA synthesis. **Why Renal Failure is the Correct Answer:** Renal failure is a **contraindication**, not an indication, for Methotrexate. MTX is primarily excreted unchanged by the kidneys (via glomerular filtration and active tubular secretion). In patients with renal impairment, the drug accumulates rapidly, leading to life-threatening systemic toxicity, including severe bone marrow suppression and mucosal ulcerations. Furthermore, high-dose MTX can cause crystalluria, further worsening renal function. **Analysis of Other Options:** * **Leukemia:** MTX is a cornerstone in the treatment of Acute Lymphoblastic Leukemia (ALL), used in both induction and maintenance phases, as well as for CNS prophylaxis (intrathecal). * **Breast Cancer:** It is a component of classic chemotherapy regimens like CMF (Cyclophosphamide, Methotrexate, and 5-Fluorouracil). * **Rheumatoid Arthritis:** In low weekly doses, MTX is the "gold standard" Disease-Modifying Antirheumatic Drug (DMARD) due to its anti-inflammatory and immunosuppressive properties. **High-Yield Clinical Pearls for NEET-PG:** * **Rescue Agent:** **Leucovorin (Folinic acid)** is used to "rescue" normal cells from MTX toxicity by bypassing the inhibited DHFR enzyme. * **Other Indications:** Choriocarcinoma (highly sensitive), Psoriasis, Ectopic pregnancy, and Osteosarcoma. * **Side Effects:** Nephrotoxicity, Hepatotoxicity (cirrhosis with long-term use), and Pulmonary fibrosis. * **Drug Interaction:** NSAIDs and Penicillins decrease the renal clearance of MTX, increasing its toxicity.

Question 407: Which of the following is NOT an alkylating agent?

A. 5-Fluorouracil (Correct Answer)
B. Melphalan
C. Cyclophosphamide
D. Chlorambucil

Explanation: The correct answer is **5-Fluorouracil (5-FU)** because it belongs to the **Antimetabolite** class of anticancer drugs, specifically the pyrimidine analogs, rather than the alkylating agents. [1], [2] **1. Why 5-Fluorouracil is the correct answer:** 5-FU acts by inhibiting the enzyme **thymidylate synthase** [1]. It mimics uracil and undergoes conversion into a "false" nucleotide (FdUMP), which prevents the synthesis of thymidine [2]. This leads to "thymineless death" of the cell. Since it interferes with metabolic pathways rather than directly cross-linking DNA strands, it is classified as an antimetabolite [1]. **2. Why the other options are incorrect:** * **Melphalan:** A nitrogen mustard derivative used primarily in Multiple Myeloma. It is a classic alkylating agent [3]. * **Cyclophosphamide:** The most widely used alkylating agent [3]. It is a prodrug activated by hepatic CYP450 into phosphoramide mustard, which causes DNA cross-linking. * **Chlorambucil:** A nitrogen mustard used mainly in Chronic Lymphocytic Leukemia (CLL) [3]. Like the others, it works by attaching alkyl groups to DNA bases (usually Guanine at the N7 position). **High-Yield Clinical Pearls for NEET-PG:** * **Mechanism of Alkylating Agents:** They form reactive carbonium ions that create **intra-strand and inter-strand DNA cross-links**, leading to apoptosis. * **Common Side Effect:** Most alkylating agents are **vesicants** and carry a risk of secondary malignancies (like AML). * **Cyclophosphamide Specifics:** Watch for **Hemorrhagic Cystitis** caused by the metabolite **Acrolein**. This is prevented by aggressive hydration and **MESNA** (Mercaptoethane sulfonate). * **5-FU Specifics:** It is often used with **Leucovorin** (folinic acid), which *potentiates* its action by stabilizing the binding of 5-FU to thymidylate synthase [1].

Question 408: Which anticancer drug(s) does not suppress bone marrow?

A. 5-FU
B. Cisplatin
C. Chlorambucil
D. Vincristine (Correct Answer)

Explanation: **Explanation:** The correct answer is **Vincristine**. **1. Why Vincristine is correct:** Vincristine is a **Vinca alkaloid** that acts as a spindle poison by binding to tubulin and inhibiting microtubule polymerization. Its unique clinical profile is characterized by **minimal bone marrow suppression** (myelosuppression). This makes it an ideal component of combination chemotherapy regimens (like MOPP or CHOP), as it can be administered alongside myelosuppressive drugs without compounding hematological toxicity. Its dose-limiting toxicity is **peripheral neuropathy** rather than leukopenia or thrombocytopenia. **2. Why the other options are incorrect:** * **5-Fluorouracil (5-FU):** An antimetabolite that inhibits thymidylate synthase. It causes significant myelosuppression, along with GI toxicity (mucositis). * **Cisplatin:** A platinum compound that causes DNA cross-linking. While its primary dose-limiting toxicity is **nephrotoxicity** and ototoxicity, it still causes moderate bone marrow suppression. * **Chlorambucil:** An alkylating agent (nitrogen mustard). Like most alkylating agents, it is highly toxic to rapidly dividing cells in the bone marrow, leading to dose-dependent myelosuppression. **3. High-Yield Clinical Pearls for NEET-PG:** * **Mnemonic for Non-myelosuppressive drugs:** "**V**ery **B**ad **C**ancer **L**eaves **A**ll **S**pare" * **V**incristine (Peripheral neuropathy) * **B**leomycin (Pulmonary fibrosis) * **C**isplatin (Nephrotoxicity/Ototoxicity) * **L**-Asparaginase (Pancreatitis/Clotting issues) * **A**driamycin/Doxorubicin (Cardiotoxicity - though it *is* myelosuppressive, its cardiotoxicity is more unique) * **S**teroids * **Vincristine vs. Vinblastine:** Remember, "Vincristine **C**risps the nerves (neurotoxicity), Vinblastine **B**lasts the marrow (myelosuppression)."

Question 409: 5-FU is the chemotherapeutic agent of choice for all except:

A. Carcinoma of Breast
B. Carcinoma of Stomach
C. Carcinoma of Pancreas (Correct Answer)
D. Carcinoma of Colon

Explanation: **Explanation:** 5-Fluorouracil (5-FU) is a pyrimidine analog that acts as an antimetabolite by inhibiting **thymidylate synthase**, thereby blocking DNA synthesis. While 5-FU is a cornerstone in the management of various solid tumors, it is no longer considered the "agent of choice" for pancreatic cancer. **Why Carcinoma of Pancreas is the correct answer:** Historically, 5-FU was used for pancreatic cancer, but modern oncology has shifted toward more effective regimens. Currently, **Gemcitabine** (a deoxycytidine analog) or the **FOLFIRINOX** regimen (which includes 5-FU but as part of a multi-drug approach) are preferred. For single-agent therapy, Gemcitabine has shown superior clinical benefit and survival rates compared to 5-FU alone in pancreatic malignancy. **Analysis of Incorrect Options:** * **Carcinoma of Colon:** 5-FU remains the backbone of treatment for colorectal cancer (e.g., FOLFOX or FOLFIRI regimens). It is the definitive drug of choice in this category. * **Carcinoma of Stomach:** 5-FU is a primary component of many gastric cancer protocols (like the FLOT regimen) and is highly effective in adenocarcinomas of the GI tract. * **Carcinoma of Breast:** 5-FU is a standard component of classical regimens like **CMF** (Cyclophosphamide, Methotrexate, 5-FU) and **FAC**, making it a drug of choice for breast cancer. **NEET-PG High-Yield Pearls:** * **Mechanism:** Irreversible inhibition of thymidylate synthase ("Thymidylate death"). * **Leucovorin (Folinic Acid) Interaction:** Unlike with Methotrexate (where it acts as a rescue), Leucovorin is given with 5-FU to **enhance** its toxicity by stabilizing the binding of 5-FU to thymidylate synthase. * **Side Effects:** Hand-foot syndrome (palmar-plantar erythrodysesthesia), myelosuppression, and mucositis. * **Pharmacogenetics:** Patients with **DPD (Dihydropyrimidine dehydrogenase) deficiency** are at high risk of severe, life-threatening toxicity from 5-FU.

Question 410: Which of the following disease-modifying antirheumatic drugs (DMARDs) acts by increasing adenosine extracellularly?

A. Methotrexate (Correct Answer)
B. Sulfasalazine
C. Azathioprine
D. Leflunomide

Explanation: **Explanation:** **Methotrexate (MTX)** is the first-line DMARD for Rheumatoid Arthritis. While it is a dihydrofolate reductase (DHFR) inhibitor at high doses (used in chemotherapy), its anti-inflammatory action at low doses is primarily mediated by **adenosine**. **Mechanism of Action:** Methotrexate inhibits the enzyme **AICAR transformylase**, leading to the intracellular accumulation of AICAR (aminoimidazole carboxamide ribonucleotide). Accumulated AICAR inhibits adenosine deaminase, resulting in an increase in the release of **adenosine** into the extracellular space. Adenosine then acts on **A2A receptors** on inflammatory cells to suppress the production of pro-inflammatory cytokines (like TNF-α and IL-1), thereby exerting its potent anti-inflammatory effect. **Analysis of Incorrect Options:** * **B. Sulfasalazine:** It is broken down into sulfapyridine and 5-ASA. Its mechanism involves inhibiting NF-κB and suppressing cytokine production, but it does not primarily act via adenosine. * **C. Azathioprine:** A prodrug of 6-mercaptopurine, it acts as a purine antimetabolite that inhibits DNA synthesis, primarily affecting T-cell and B-cell proliferation. * **D. Leflunomide:** It inhibits the enzyme **dihydroorotate dehydrogenase (DHODH)**, which blocks *de novo* pyrimidine synthesis, leading to G1 cell cycle arrest in lymphocytes. **High-Yield NEET-PG Pearls:** * **DOC:** Methotrexate is the "Anchor Drug" for Rheumatoid Arthritis. * **Supplementation:** Always co-prescribe **Folic acid** to reduce GI toxicity and mucosal ulcers without compromising efficacy. * **Contraindication:** It is strictly **teratogenic** (causes fetal cranial anomalies) and contraindicated in pregnancy. * **Monitoring:** Watch for hepatotoxicity (monitor LFTs) and pulmonary fibrosis.

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

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Immunotherapy

Practice Questions

Management of Chemotherapy Side Effects

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