Introduction
Plant products play a vital role in drug discovery; etoposide, a semisynthetic derivative of podophyllotoxin, is a key anticancer agent studied in pharmaceutics and pharmacology. This concise review for B. Pharm students covers etoposide’s origin, chemical class, mechanism of action as a topoisomerase II inhibitor, cell-cycle specificity, pharmacokinetics (absorption, CYP3A4 metabolism, protein binding, excretion), formulations (IV, oral, etoposide phosphate), therapeutic uses, adverse effects (myelosuppression, secondary leukemia), resistance mechanisms (P-gp, mutations), and analytical and stability considerations. Emphasis is on clinical significance, dosing principles, and formulation challenges to prepare you for exam and practice. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. Which plant-derived compound is the precursor for semisynthetic etoposide?
- Podophyllum species (podophyllotoxin)
- Taxus brevifolia (paclitaxel)
- Camptotheca acuminata (camptothecin)
- Digitalis purpurea (digoxin)
Correct Answer: Podophyllum species (podophyllotoxin)
Q2. Etoposide belongs to which chemical class?
- Alkylating agent
- Epipodophyllotoxin derivative
- Anthracycline antibiotic
- Vinca alkaloid
Correct Answer: Epipodophyllotoxin derivative
Q3. What is the primary mechanism of action of etoposide?
- Alkylation of DNA guanine residues
- Intercalation into DNA helix without enzyme interaction
- Stabilizes topoisomerase II–DNA cleavable complex causing double-strand breaks
- Inhibition of microtubule polymerization
Correct Answer: Stabilizes topoisomerase II–DNA cleavable complex causing double-strand breaks
Q4. During which phases of the cell cycle is etoposide most active?
- G0 phase only
- M phase only
- S and G2 phases
- G1 phase only
Correct Answer: S and G2 phases
Q5. Which of the following correctly describes standard clinical formulations of etoposide?
- Only oral; intravenous formulations are not available
- IV and oral; etoposide phosphate is a water‑soluble prodrug
- Only topical formulations for localized tumors
- Inhalation aerosol form is the standard
Correct Answer: IV and oral; etoposide phosphate is a water‑soluble prodrug
Q6. What is the major dose‑limiting toxicity of etoposide?
- Cardiotoxicity
- Myelosuppression (neutropenia)
- Neurotoxicity
- Renal tubular necrosis
Correct Answer: Myelosuppression (neutropenia)
Q7. Etoposide use is associated with an increased risk of which secondary malignancy?
- Basal cell carcinoma
- Therapy-related acute myeloid leukemia (t-AML) with 11q23 abnormalities
- Chronic lymphocytic leukemia after 10 years
- Kaposi sarcoma
Correct Answer: Therapy-related acute myeloid leukemia (t-AML) with 11q23 abnormalities
Q8. Which cytochrome P450 isoform primarily metabolizes etoposide?
- CYP2D6
- CYP1A2
- CYP3A4
- CYP2C9
Correct Answer: CYP3A4
Q9. Which drug is likely to reduce plasma etoposide concentrations by inducing its metabolism?
- Ketoconazole
- Rifampicin
- Fluconazole
- Itraconazole
Correct Answer: Rifampicin
Q10. One mechanism of tumor resistance to etoposide involves which protein?
- Topoisomerase I overexpression
- P-glycoprotein (MDR1) mediated efflux
- Increased glutathione peroxidase activity
- Inhibition of CYP3A4
Correct Answer: P-glycoprotein (MDR1) mediated efflux
Q11. What is the approximate elimination half‑life of etoposide in adults?
- Approximately 1 hour
- Approximately 6 hours
- Approximately 24 hours
- Approximately 72 hours
Correct Answer: Approximately 6 hours
Q12. Which statement best describes etoposide’s plasma protein binding?
- Negligible protein binding (<10%)
- Moderate protein binding (~50%)
- High protein binding (~94%)
- Protein binding is highly variable and unpredictable
Correct Answer: High protein binding (~94%)
Q13. How is etoposide eliminated from the body?
- Exclusively renal excretion of unchanged drug
- Exclusively hepatic metabolism with no renal clearance
- Both renal excretion and hepatic metabolism
- Exhalation as volatile metabolites
Correct Answer: Both renal excretion and hepatic metabolism
Q14. What is the clinical advantage of etoposide phosphate over etoposide base?
- Greater oral bioavailability but more GI toxicity
- Water-soluble prodrug reducing solvent-related toxicity for IV use
- Longer half-life requiring less frequent dosing
- Completely avoids CYP3A4 metabolism
Correct Answer: Water-soluble prodrug reducing solvent-related toxicity for IV use
Q15. Etoposide is a core component of which standard chemotherapy regimen for testicular cancer?
- CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone)
- BEP (bleomycin, etoposide, cisplatin)
- TAC (docetaxel, doxorubicin, cyclophosphamide)
- FOLFOX (folinic acid, 5-FU, oxaliplatin)
Correct Answer: BEP (bleomycin, etoposide, cisplatin)
Q16. Which of the following is a common reversible adverse effect of etoposide?
- Permanent peripheral neuropathy
- Alopecia
- Severe chronic cardiomyopathy
- Pulmonary fibrosis as a direct effect
Correct Answer: Alopecia
Q17. What laboratory parameter should be monitored routinely during etoposide therapy?
- Serum amylase only
- Complete blood count (CBC)
- Fasting blood glucose
- Urine osmolality
Correct Answer: Complete blood count (CBC)
Q18. The DNA damage caused by etoposide is best described as:
- Single-strand DNA nicks only
- Cross-linking of DNA strands
- Double-strand DNA breaks via topoisomerase II stabilization
- Oxidative base modifications without strand breaks
Correct Answer: Double-strand DNA breaks via topoisomerase II stabilization
Q19. Etoposide should be avoided or used with extreme caution in which patient population?
- Pregnancy due to teratogenicity
- Patients with controlled hypertension
- Patients with lactose intolerance
- Patients with hyperthyroidism
Correct Answer: Pregnancy due to teratogenicity
Q20. Which analytical technique is most commonly used to quantify etoposide in plasma samples?
- Gas chromatography without derivatization
- High-performance liquid chromatography (HPLC)
- Colorimetric assay using biuret reagent
- Simple UV spectrophotometry without separation
Correct Answer: High-performance liquid chromatography (HPLC)
Q21. Which clinical complication during etoposide therapy requires immediate management?
- Transient mild alopecia
- Febrile neutropenia
- Minor nausea responsive to antiemetic
- Mild alopecia
Correct Answer: Febrile neutropenia
Q22. A tumor becoming resistant to etoposide via reduced target enzyme activity is due to:
- Overexpression of topoisomerase II
- Mutation or downregulation of topoisomerase II
- Increased DNA uptake of etoposide
- Enhanced DNA repair of single-strand breaks only
Correct Answer: Mutation or downregulation of topoisomerase II
Q23. Why is oral bioavailability of etoposide variable between patients?
- Because it is administered as an inhaled drug
- Variable oral bioavailability due to poor and dose-dependent absorption and first-pass metabolism
- Oral forms are identical to IV so variability is negligible
- Because etoposide is not absorbed unless taken with high-fat meals only
Correct Answer: Variable oral bioavailability due to poor and dose-dependent absorption and first-pass metabolism
Q24. Which formulation excipient in some etoposide preparations can cause hypersensitivity reactions?
- Polysorbate 80 solvent may cause hypersensitivity reactions
- Lactose monohydrate causes allergic reactions in all patients
- Sodium chloride is responsible for anaphylaxis
- Glycerin causes severe hypersensitivity
Correct Answer: Polysorbate 80 solvent may cause hypersensitivity reactions
Q25. Which of the following is a water‑soluble prodrug of etoposide used to improve IV administration?
- Etoposide acetate
- Etoposide phosphate
- Etoposide sulfate
- Etoposide citrate
Correct Answer: Etoposide phosphate
Q26. Before administering etoposide in patients with liver impairment you should check:
- Cardiac enzymes only
- Renal electrolytes only
- Liver function tests (AST, ALT, bilirubin)
- Thyroid function tests
Correct Answer: Liver function tests (AST, ALT, bilirubin)
Q27. Etoposide is a key chemotherapeutic drug for which of the following cancers?
- Small cell lung carcinoma
- Basal cell carcinoma
- Localized prostate cancer only
- Non-invasive skin papilloma
Correct Answer: Small cell lung carcinoma
Q28. The typical latency period for etoposide-associated therapy‑related AML is:
- Less than 6 months
- 1–3 years
- 5–10 years
- Over 10 years
Correct Answer: 1–3 years
Q29. Which drug, by inhibiting P‑glycoprotein, can increase intracellular etoposide concentrations and toxicity?
- Rifampicin
- Verapamil
- Phenytoin
- Carbamazepine
Correct Answer: Verapamil
Q30. For routine plasma quantification of etoposide in pharmacokinetic studies, the preferred detection method is:
- Mass spectrometry without chromatographic separation
- HPLC with UV detection
- Nephalometric turbidity assay
- Paper chromatography followed by colorimetric scanning
Correct Answer: HPLC with UV detection
