CONCEPTUAL SUMMARY

CLASSIFICATION OF ANTINEOPLASTIC AGENTS

Alkylating Agents

Add alkyl groups to DNA bases → interstrand and intrastrand cross-links → inhibit DNA synthesis → cell death. Cell-cycle NON-SPECIFIC (CCNS) — effective throughout any cell cycle phase; effective against large, slowly growing tumors. Examples:

• Cyclophosphamide (bifunctional nitrogen mustard prodrug — activated in liver), ifosfamide, melphalan, busulfan, carmustine, chlorambucil, bendamustine. Key toxicity of cyclophosphamide and ifosfamide: HEMORRHAGIC CYSTITIS (from toxic metabolite acrolein) — prevented with mesna (binds acrolein). Cyclophosphamide emetogenic risk: MEC at doses ≤ 1,500 mg/m² → HEC at doses > 1,500 mg/m² OR in AC combination.
• Antimetabolites: Structural analogs of normal metabolites — interfere with DNA and RNA synthesis.
  • Antifolates: methotrexate (inhibits dihydrofolate reductase — blocks folate conversion), pemetrexed (inhibits multiple folate-dependent enzymes).
  • Pyrimidine analogs: 5-fluorouracil (inhibits thymidylate synthase — blocks dTMP synthesis), capecitabine (oral prodrug of 5-FU), cytarabine (ara-C — incorporated into DNA, inhibits DNA polymerase), gemcitabine.
  • Purine analogs: cladribine, fludarabine, mercaptopurine, azathioprine. Cell-cycle SPECIFIC (S-phase).
• Antimicrotubule Agents:
  • Taxanes: paclitaxel, docetaxel — STABILIZE microtubules (prevent depolymerization) → mitotic arrest.
  • Vinca alkaloids: vincristine, vinblastine, vinorelbine — INHIBIT microtubule polymerization (prevent formation) → mitotic arrest. Cell-cycle specific (M-phase).
• Topoisomerase Inhibitors (Enzyme Inhibitors):
  • Topoisomerase I inhibitors: irinotecan, topotecan (camptothecins) — stabilize cleavable complex → single-stranded DNA breaks.
  • Topoisomerase II inhibitors: etoposide, teniposide (epipodophyllotoxins) → double-stranded DNA breaks; anthracyclines (doxorubicin, daunorubicin, idarubicin, epirubicin) — also inhibit topo II + intercalate DNA.
• Tyrosine Kinase Inhibitors (TKIs): Block ATP-binding site of tyrosine kinases → inhibit cell growth signaling.
  • BCR-ABL: imatinib, nilotinib, dasatinib, bosutinib, ponatinib (CML).
  • EGFR: erlotinib, gefitinib, osimertinib.
  • VEGFR: sorafenib, sunitinib.
  • HER2: lapatinib, tucatinib.
  • BRAF: vemurafenib, dabrafenib, encorafenib.
  • MEK: trametinib, cobimetinib, binimetinib.
• Hormonal Therapy:
  • Aromatase inhibitors: anastrozole, letrozole, exemestane (postmenopausal).
  • SERMs: tamoxifen (pre- and postmenopausal), raloxifene (postmenopausal only).
  • LHRH agonists: leuprolide, goserelin — cause initial testosterone FLARE → give antiandrogens (bicalutamide, flutamide) BEFORE and during initial LHRH agonist therapy to prevent flare symptoms.
  • LHRH antagonists: degarelix, relugolix — no testosterone flare — antiandrogens NOT required upfront.
  • CYP17 inhibitor: abiraterone (requires prednisone).

PREMEDICATION REQUIREMENTS

• Docetaxel: corticosteroids pre- AND POST-medication (dexamethasone before and after) — prevents FLUID RETENTION (capillary leak syndrome) and hypersensitivity reactions. This is the UNIQUE feature of docetaxel — corticosteroids both before and after the dose.
• Paclitaxel: corticosteroids + H1 antagonist (diphenhydramine) + H2 antagonist (ranitidine/famotidine) — before ONLY — prevents hypersensitivity from Cremophor EL solvent.
• Ifosfamide/high-dose cyclophosphamide: mesna — prevents hemorrhagic cystitis (binds acrolein).
• Irinotecan: atropine — prevents acute cholinergic diarrhea (within 24 hours).
• High-dose methotrexate: leucovorin rescue (calcium folinate) — started 12–42 hours after MTX dose, continued until MTX levels < 0.1 µM.
• Anthracyclines (extravasation): dexrazoxane (Totect) — antidote for extravasation.
• Vinca alkaloids (extravasation): hyaluronidase + warm compresses — antidote for extravasation.

HIGH-DOSE CYTARABINE (ARA-C) OCULAR TOXICITY: Doses > 1,000 mg/m² → chemical conjunctivitis. Prevention: dexamethasone 0.1% ophthalmic drops every 4–6 hours for 7 days post-therapy. Other high-dose cytarabine toxicities: CNS toxicity (ataxia, cerebellar dysfunction), excessive myelosuppression.

SPECIFIC DRUG TOXICITIES

• Vincristine: SIADH (inappropriate ADH secretion), dose-limiting NEUROLOGIC toxicity (peripheral neuropathy, constipation, paralytic ileus), minimal myelosuppression. Max dose cap: 2 mg to limit neurotoxicity.
• Vinblastine: primary toxicity is MYELOSUPPRESSION (dose-limiting leukopenia) — much less neurotoxic than vincristine.
• Vinorelbine: minimal emetogenic risk (vinca alkaloid); myelosuppression.
• Ifosfamide: dose-limiting hemorrhagic cystitis (acrolein) — mesna required; CNS toxicity (encephalopathy).
• Capecitabine: hand-foot syndrome (palmar-plantar erythrodysesthesia) and diarrhea are dose-limiting toxicities.
• Bleomycin: pulmonary toxicity (pulmonary fibrosis) — cumulative dose-dependent — monitor PFTs (DLCO); NO bone marrow suppression; requires NO standard premedication (monitor only). Avoid high-flow oxygen with bleomycin (increases pulmonary toxicity).
• Anthracyclines: cardiotoxicity (dose-dependent cardiomyopathy from free radical generation) — track cumulative lifetime dose — MUGA scan baseline. Dexrazoxane may be used as cardioprotective in select patients. Red urine discoloration (not hematuria).
• Mitoxantrone: used as anthracycline alternative with LESS cardiotoxicity (does not form oxygen-free radicals).
• Cisplatin: nephrotoxicity (dose-limiting), ototoxicity, neuropathy, severe nausea/vomiting (most emetogenic platinum agent). Requires aggressive IV hydration. Contraindicated CrCl < 60 mL/min.
• Glucarpidase: used for impaired methotrexate clearance (elevated MTX levels with renal dysfunction) — enzyme that rapidly degrades methotrexate. Leucovorin is the standard rescue agent; glucarpidase is for specific clearance-impaired situations.

MOLECULAR TARGETS AND ASSOCIATED THERAPIES (HIGH-YIELD)

• CML: t(9;22) BCR-ABL → imatinib, dasatinib, nilotinib, bosutinib, ponatinib.
• AML APL: t(15;17) PML-RARA → ATRA + arsenic trioxide.
• AML FLT3-ITD: midostaurin. AML IDH1: ivosidenib. AML IDH2: enasidenib.
• NSCLC
  • EGFR: osimertinib (preferred).
  • ALK: lorlatinib, alectinib, brigatinib.
  • BRAF V600E: dabrafenib + trametinib.
  • KRAS G12C: sotorasib.
• CRC
  • KRAS/NRAS wild-type: cetuximab, panitumumab (EGFR antibodies).
  • BRAF V600E: encorafenib + cetuximab.
  • MSI-H/dMMR: pembrolizumab.
• Breast
  • HER2+: trastuzumab, pertuzumab, T-DM1, T-DXd.
  • PIK3CA: alpelisib + fulvestrant.
  • Breast/Ovarian BRCA1/2: olaparib, talazoparib, niraparib, rucaparib (PARP inhibitors).
• Melanoma BRAF V600E: vemurafenib, dabrafenib, encorafenib + MEK inhibitor.
• GIST KIT/PDGFRA: imatinib → sunitinib → regorafenib → ripretinib.
• Thyroid RET: selpercatinib.
• mCRPC HRR: olaparib (any HRR except PPP2R2A), rucaparib (BRCA1/2 only), talazoparib + enzalutamide (PALB2/BRCA).
• Glioma IDH1/2: vorasidenib (IDH inhibitor).

IDH MUTATION BIOLOGY: IDH mutation → produces oncometabolite 2-hydroxyglutarate (2-HG) → inhibits alpha-ketoglutarate-dependent demethylases → global HYPERMETHYLATION (G-CIMP) → blocks cellular differentiation. Found in oligodendrogliomas (with 1p/19q codeletion) and some astrocytomas/GBM.

1p/19q CODELETION: Defines oligodendroglioma (with IDH mutation). Associated with favorable prognosis. Guides treatment: radiation followed by PCV chemotherapy.

PRACTICE QUESTIONS — PHARMACOLOGY AND MOLECULAR ONCOLOGY

Cyclophosphamide is classified as which type of antineoplastic agent?

A. Alkylating agent
B. Enzyme inhibitor
C. Antimicrotubule
D. Antimetabolite

Explanation:

• Cyclophosphamide is a bifunctional alkylating agent (nitrogen mustard class). It is a PRODRUG that must be activated in the liver to form its active cytotoxic metabolites. It works by transferring alkyl groups to DNA bases → forming interstrand and intrastrand cross-links → inhibiting DNA synthesis → cell death. It is cell-cycle NON-SPECIFIC (CCNS) — effective in any phase, especially useful against large, slowly growing tumors. Key toxicities: myelosuppression (dose-limiting), alopecia, and hemorrhagic cystitis (from the toxic metabolite acrolein — prevented with mesna and high fluid intake at high doses). Emetogenic risk: MEC at ≤ 1,500 mg/m² but HEC when used in the AC combination or at doses > 1,500 mg/m².
• Enzyme inhibitors (option B) include topoisomerase inhibitors (irinotecan, etoposide, anthracyclines) and TKIs.
• Antimicrotubules (option C) include taxanes and vinca alkaloids.
• Antimetabolites (option D) include methotrexate, 5-FU, and cytarabine.

Which drug requires both pre- AND post-medication with corticosteroids to prevent the fluid retention associated with it?

A. Docetaxel
B. Ifosfamide
C. Vinorelbine
D. Mesna

Explanation:

• Docetaxel (a taxane) requires dexamethasone premedication both BEFORE and AFTER the dose (typically dexamethasone 8 mg PO twice daily starting the day before chemotherapy and continuing for 2 days after) — this UNIQUE pre- and post-dosing schedule specifically prevents FLUID RETENTION (capillary leak syndrome/edema) and reduces hypersensitivity reactions. This is a high-yield distinction: docetaxel = corticosteroids before AND after.
• Paclitaxel (the other taxane) requires steroids + H1 + H2 blockers BEFORE only — for hypersensitivity from Cremophor solvent.
• Ifosfamide (option B) requires MESNA (not corticosteroids) to prevent hemorrhagic cystitis from acrolein.
• Vinorelbine (option C) does not require corticosteroid premedication.
• Mesna (option D) is a protective agent itself — it is given WITH ifosfamide, not the drug requiring corticosteroids.

What is the antidote/rescue agent for methotrexate toxicity?

A. Calcium folinate (leucovorin)
B. Dexrazoxane
C. Glucarpidase
D. Hyaluronidase

Explanation:

• Methotrexate is a folate antagonist that competitively inhibits dihydrofolate reductase — blocking folate conversion needed for DNA synthesis. High-dose methotrexate therapy can cause lethal toxicity to healthy cells without rescue. Calcium folinate (leucovorin) is a REDUCED form of folate that does not require dihydrofolate reductase to enter cells — it directly replenishes folate metabolites needed for DNA synthesis, "rescuing" normal cells from methotrexate toxicity. Timing: rescue must be initiated within 42 hours of the methotrexate dose; continue until MTX levels < 0.1 µM. Third-space fluids (ascites, pleural effusions) can slow MTX clearance and require prolonged rescue.
• Dexrazoxane (option B): antidote for ANTHRACYCLINE extravasation (not methotrexate).
• Glucarpidase (option C): enzyme used in modern practice for impaired methotrexate clearance (elevated MTX levels with renal dysfunction) — rapidly degrades methotrexate; is NOT the primary foundational rescue agent (leucovorin is).
• Hyaluronidase (option D): antidote for VINCA ALKALOID extravasation — administered with warm compresses.

Which drug causes conjunctivitis when used in high doses?

A. Doxorubicin
B. Gemcitabine
C. Cytarabine
D. Cladribine

Explanation:

• High-dose cytarabine (doses > 1,000 mg/m²) causes CHEMICAL CONJUNCTIVITIS. Prevention: dexamethasone 0.1% ophthalmic eye drops administered every 4–6 hours for 7 days following completion of high-dose therapy — this is MANDATORY premedication. Additional high-dose cytarabine toxicities: CNS toxicity (ataxia, cerebellar dysfunction), excessive myelosuppression/thrombocytopenia.
• Doxorubicin (option A) — anthracycline causing cardiotoxicity and RED urine discoloration; not associated with conjunctivitis.
• Gemcitabine (option B) — pyrimidine analog used for solid tumors (pancreatic, lung cancers); not known for ocular toxicity requiring eye drops.
• Cladribine (option D) — purine analog notable for immunosuppression of T-helper cells; not associated with ocular toxicity.

Which drug causes SIADH (syndrome of inappropriate antidiuretic hormone secretion)?

A. Ifosfamide
B. Vincristine
C. Capecitabine
D. Vinblastine

Explanation:

• Vincristine is a vinca alkaloid specifically known to cause SIADH. Its dose-limiting toxicity is NEUROLOGIC — peripheral neuropathy, constipation, and paralytic ileus. Vincristine notably has MINIMAL myelosuppression compared to other vinca alkaloids. Maximum dose cap: 2 mg per dose to limit neurotoxicity.
• Ifosfamide (option A) — associated with dose-limiting hemorrhagic cystitis (acrolein metabolite) and CNS encephalopathy — not the classic SIADH agent.
• Capecitabine (option C) — a pyrimidine analog (oral 5-FU prodrug) with dose-limiting hand-foot syndrome and diarrhea — not associated with SIADH.
• Vinblastine (option D) — same vinca alkaloid class but with dose-limiting MYELOSUPPRESSION (leukopenia) rather than the neurologic/SIADH profile of vincristine; much less neurotoxic.

Antiandrogens should be taken prior to treatment and in combination with which medication?

A. Tamoxifen
B. Aromatase inhibitors
C. LHRH analogues (agonists)
D. LHRH antagonists

Explanation:

• LHRH agonists (leuprolide, goserelin) cause an initial TESTOSTERONE SURGE (flare) when therapy begins — LH and FSH spike before suppression occurs. This flare can trigger WORSENING BONE PAIN and disease exacerbation (especially in prostate cancer with bone metastases). To prevent this: antiandrogens (bicalutamide, flutamide, nilutamide) are administered BEFORE the first LHRH agonist dose and continued for the first several weeks to block androgen receptor activity during the testosterone surge.
• LHRH antagonists (option D) — degarelix, relugolix — directly block LHRH receptors WITHOUT an initial testosterone surge; therefore, antiandrogens are NOT required upfront with antagonists.
• Tamoxifen (option A) — SERM for breast cancer; not relevant to androgen suppression.
• Aromatase inhibitors (option B) — reduce estrogen in postmenopausal breast cancer; not related to androgen/prostate cancer flare prevention.

BK is a 56-year-old female with breast cancer presenting with diarrhea, nausea and vomiting, increased thirst, and fatigue. Which symptoms are consistent with hypercalcemia?

A. Nausea and vomiting, increased thirst, fatigue
B. Fatigue, diarrhea, nausea and vomiting
C. Increased thirst, fatigue, diarrhea
D. Diarrhea, nausea and vomiting, increased thirst

Explanation: Classic hypercalcemia signs and symptoms span GI, renal, neurologic, and cardiac systems.

• GI symptoms: nausea, vomiting, anorexia, and CONSTIPATION (NOT diarrhea — decreased smooth muscle tone causes constipation).
• Renal/fluid: polydipsia (increased thirst), polyuria, dehydration.
• Neurologic/systemic: fatigue, weakness, confusion, lethargy.
• Cardiac: shortened QT interval, arrhythmias. Diarrhea is NOT a symptom of hypercalcemia — diarrhea is more characteristic of chemotherapy agents (irinotecan, 5-FU, capecitabine) or other causes. BK has diarrhea — this is the distractor that should be excluded from the hypercalcemia symptom cluster. Options B, C, and D all incorrectly include diarrhea — making A the only correct answer.

Which of the following correctly matches the chemotherapy agent with its appropriate rescue agent or protective premedication?

Key distinctions for exam: Docetaxel = steroids before AND after (unique). Paclitaxel = steroids + antihistamines before ONLY. Mesna works by binding ACROLEIN (the toxic metabolite of ifosfamide/cyclophosphamide) — it does NOT prevent all ifosfamide toxicities, only cystitis. Leucovorin is the RESCUE agent for methotrexate — not an antidote; it bypasses the blocked enzyme. Dexrazoxane has two roles: (1) cardioprotective agent with high cumulative anthracycline doses in select patients; (2) antidote for anthracycline extravasation.

Match each molecular marker to the most appropriate targeted therapy:

Which of the following statements about chemotherapy agents is TRUE?

A. Cyclophosphamide is a cell-cycle specific agent that only works during S-phase
B. Vinca alkaloids stabilize microtubules and prevent depolymerization
C. Methotrexate inhibits dihydrofolate reductase, blocking the conversion of folic acid to reduced folate metabolites
D. Topoisomerase I inhibitors cause double-stranded DNA breaks

Explanation:

• Methotrexate competitively inhibits dihydrofolate reductase (DHFR) — the enzyme responsible for converting folic acid into reduced folate metabolites needed for DNA synthesis. This is the correct mechanism.
• Option A is incorrect — cyclophosphamide is a cell-cycle NON-SPECIFIC (CCNS) alkylating agent — it works in ANY phase of the cell cycle.
• Option B is incorrect — this describes TAXANES (paclitaxel, docetaxel), which stabilize microtubules. VINCA ALKALOIDS (vincristine, vinblastine, vinorelbine) do the OPPOSITE — they INHIBIT microtubule polymerization (prevent formation).
• Option D is incorrect — TOPOISOMERASE I inhibitors (irinotecan, topotecan) cause SINGLE-stranded DNA breaks. Topoisomerase II inhibitors (etoposide, anthracyclines) cause DOUBLE-stranded DNA breaks.

Which of the following correctly describes the mechanism of IDH mutation in cancer?

A. IDH mutation activates BRAF → MEK → ERK signaling pathway
B. IDH mutation produces 2-hydroxyglutarate → inhibits DNA demethylases → global hypermethylation → blocks differentiation
C. IDH mutation causes chromosome instability → monosomy 7
D. IDH mutation activates androgen receptor signaling → prostate cancer progression

Explanation:

• Mutated IDH (isocitrate dehydrogenase) produces the oncometabolite 2-hydroxyglutarate (2-HG) instead of normal alpha-ketoglutarate. 2-HG inhibits alpha-ketoglutarate-dependent DNA demethylase enzymes → global DNA HYPERMETHYLATION (CpG island methylator phenotype/G-CIMP) → disrupts normal gene expression → BLOCKS cellular differentiation.
• IDH mutations are found in oligodendrogliomas (with 1p/19q codeletion), some AML subtypes, and some lower-grade gliomas. They are early driver mutations and key diagnostic markers. Targeted therapy: ivosidenib (IDH1), enasidenib (IDH2) for AML; vorasidenib for IDH-mutant gliomas. Options A, C, and D describe unrelated molecular pathways.

3. Which of the following drugs contains a black box warning for cardiac toxicity?

• A. Temozolomide (7%)
• B. Irinotecan (10%)
• C. Etoposide (15%)
• D. Trastuzumab (68%)

• For board exams and clinical practice, it is important to recognize those chemotherapeutic agents classically associated with cardiac toxicity.
• They include daunorubicin (Cerubidine) and doxorubicin (Adriamycin), mainly in cumulative doses > 400 mg/m^².
• Trastuzumab (Herceptin) is an IgG monoclonal antibody most commonly used for breast cancer.
• Lastly, the tyrosine kinase inhibitors, lapatinib (Tykerb), and sunitinib (Sutent).

9. Imatinib was the first molecularly targeted tyrosine kinase inhibitor (TKI) approved in the US in 2001 against BCR-ABL for the treatment of chronic myelogenous leukemia. Since then, many TKIs have been approved for the treatment of various cancers. These agents are different in that they inhibit multiple tyrosine kinases. Which of the following is true regarding the multigated TKIs?

• A. Associated toxicities may be less than those of other agents (68%)
• B. May be more effective against some resistant tumors (72%)
• C. Unaffected by CYP450 enzyme system (4%)
• D. May be taken without regard to meals (63%)

• The second answer choice is best as cancer is associated with multiple pathophysiologic mechanisms. Therefore, targeting the tumor through inhibition of multiple pathways may provide better outcomes. A good example of this is sunitinib, which has been effective in the treatment of gastrointestinal stromal tumor (GIST) after imatinib failure.
• As targeted agents inhibit multiple tyrosine kinase activities, there is an increased risk of toxicities (first answer option).
• Multitargeted TKIs like sunitinib, sorafenib, and lapatinib have CYP450 drug-drug interaction potential (third answer choice), and meals do affect the pharmacokinetic/pharmacodynamics of these agents, including sorafenib and lapatinib (last answer choice).
• Multitargeted TKIs such as sunitinib, sorafenib, and lapatinib are similar to the first-generation TKIs in that they have a potential for CYP450 drug interactions and drug-food interactions. However, they may also be more effective against resistant tumors and are associated with an increased risk of toxicities.
• Sunitinib was the first drug to show clinical benefit in imatinib-resistant GIST. However, resistance to sunitinib may generally develop within one year of treatment. In patients with GIST who have developed resistance to imatinib and sunitinib, regorafenib (another multitargeted TKI) has been shown to improve progression-free survival compared to placebo.

12. LJ is a 65-year-old female receiving panitumumab for her chemotherapy-resistant metastatic colorectal cancer. What practical information should you share with LJ?

• A. Protect yourself from sun exposure since panitumumab may increase risk of sunburns. (6%)
• B. Avoid fresh fruits and vegetables since they harbor bacteria that could increase infection risk. Only eat fruits that can be peeled and vegetables that are cooked before consumption. (13%)
• C. Maintain hydration since panitumumab may cause kidney damage. (16%)
• D. Always wear shoes and protect your feet since this agent may produce neuropathy and lead to decrease sensations in your extremities. (11%)

• All epidermal growth factor receptor (EGFR) inhibitors can cause skin irritation and predispose patients to develop an acneiform rash on the face and trunk, skin desquamation, folliculitis, dry skin, paronychia, or pruritus.
• Rash is a frequent toxicity occurring in over 90% of patients on cetuximab (Erbitux) and panitumumab (Vectibix).
• EGFR inhibitors seem to produce abnormalities leading to follicular and interfollicular inflammation, bacterial overgrowth, dry skin, and sun or radiation sensitivity.

13. Which of the following toxicities is NOT typical of the PD-1 inhibitors (pembrolizumab and nivolumab)?

• A. Diarrhea (12%)
• B. Elevated liver enzymes (7%)
• C. Proteinuria (57%)
• D. Hypothyroidism (24%)

• Proteinuria is not a common side effect of these drugs.
• PD-1 inhibitors, such as pembrolizumab and nivolumab, work by preventing T cell inactivation from producing antitumor activity. Like the other checkpoint inhibitors, the PD-1 inhibitors are known for causing a unique set of toxicities called immune-mediated adverse events (IAAEs). These include pneumonitis, colitis, hepatitis, endocrinopathies (hypophysitis or hypothyroidism), renal insufficiency, rash, and pruritis.
• While the time to onset of these toxicities varies, treatment typically consists of immunosuppression using corticosteroids.
• PD-1 inhibitors can cause immune-mediated adverse events such as pneumonitis, colitis, hepatitis, endocrinopathies (hypophysitis or hypothyroidism), renal insufficiency, rash, and pruritus.
• Dose modifications based on the severity of these immune-mediated toxicities are listed in the package inserts for nivolumab and pembrolizumab.
• Patients who receive allogeneic stem cell transplants after PD-1 inhibitors should be monitored for hepatic vein-occlusive disease, graft versus host disease and other immune-mediated adverse reactions.

15. Which of the enzymatic pathways involved in drug metabolism make up the greatest contribution in the clearance of drugs?

• A. N-acetyltransferase (NAT) (2%)
• B. Cytochrome P450 (CYP) (83%)
• C. UDP-glucuronosyltransferase (UGT) (14%)
• D. Flavin monooxygenase (FMO) (1%)

16. Which of the following phase II metabolic pathways is most commonly involved in drug metabolism and can also be used for a drug-drug interaction site?

• A. Cytochrome P450 3A4 (CYP3A4) (34%)
• B. UDP-glucuronosyltransferase (UGT) (54%)
• C. P-glycoprotein (Pgp) (11%)
• D. N-acetyltransferase (NAT) (2%)

• Only choices B and D are phase II enzymes involved in drug metabolism, and UDP glucuronyltransferase (UGT) is the most common of the two. Within the UGT enzymes, UGT1A1, 1A4, and 2B7 make up the majority of enzymes involved in drug metabolism.
• Choice A is a phase I or CYP450 metabolic enzyme involved in the oxidation/reduction of drugs. Choice C is an efflux cell membrane transporter and does not “metabolize” drugs.

17. True or False: With medications with some degree of protein binding to albumin, it is the free fraction or unbound medication that exerts a biological or pharmacological effect.

A. True (95%)
B. False (5%)

• Only free or unbound drug can enter into tissue or interact with a cell membrane receptor to initiate or modulate a biological/pharmacological effect.
• This can be clinically important, especially for highly protein-bound drugs that get displaced from their protein binding sites and become free to exert their effects.
• A good example of this is phenytoin (Dilantin) - which is an anticonvulsant used in the management of epilepsy.
• Only medications in their free or unbound state can exert their pharmacologic properties.
• Most medications bind to the protein, albumin, but some also bind to alpha-1 acid glycoprotein and globulins.
• Alpha-1 acid glycoprotein is an acute phase reactant whose levels are always changing.

18. Chemotherapy vesicants that cause tissue damage by DNA binding tend to cause severe and prolonged skin toxicity. Which of the following agents leads to tissue destruction through DNA binding when the patient experiences extravasation?

• A. Vinblastin (28%)
• B. Daunorubicin (52%)
• C. Docetaxel (10%)
• D. Bevacizumab (10%)

• Vesicant chemotherapy agents can be categorized as DNA-binding (alkylating agents, anthracyclines, dactinomycin, mitomycin, mitoxantrone) and DNA non-binding (vinca alkaloids, taxanes). Compared to DNA-binding vesicants, non-DNA-binding vesicants are eventually metabolized by the tissue and more easily neutralized.
• The second answer option is correct, as anthracyclines (daunorubicin) cause tissue damage by ‘DNA binding’ when extravasated.
• Vinca alkaloids (vinblastine) and taxanes (docetaxel) are considered ‘non-DNA binding’.
• Alkylating agents and anthracyclines are considered “DNA-binding” agents and cause significant extravasation injury.
• Although dexrazoxane (Zinecard) has been used for many years to reduce anthracycline-induced cardiotoxicity, the FDA eventually approved dexrazoxane (Totext in 2007 to treat anthracycline extravasation.

23. Which of the following is a side effect of mesna?

• A. Neurotoxicity (11%)
• B. Hyponatremia (23%)
• C. Hemorrhagic cystitis (14%)
• D. False-positive ketone tests (62%)

• Mesna is used for the prevention of hemorrhagic cystitis associated with ifosfamide or high-dose cyclophosphamide.
• However, it may result in false-positive tests for urinary ketones.

28. Which of the following does not require a dose adjustment for renal insufficiency?

• A. Ixabepipone (49%)
• B. Eribulin (19%)
• C. Methotrexate (16%)
• D. Capecitabine (16%)

• Ixabepiprone (ixempra) does not require dose adjustment if the creatinine clearance is over 30 mL/min. It has not been sufficiently studied below that level.
• About 65% of ixabepiprone is excreted in the feces, whereas 21% is excreted in the urine and thus is less dependent on kidney function for renal elimination.

39. What type of IgG monoclonal antibody is panitumumab?

• A. Chimeric (7%)
• B. Humanized (21%)
• C. Human (68%)
• D. Mouse (14%)

• Panitumumab (Vectibix) is a recombinant, fully human IgG kappa monoclonal antibody that binds to the epidermal growth factor receptor.
• The monoclonal antibody nomenclature depicts before the ‘-mab’ suffix is the letter ‘u’ = human’.

40. Which of the CYP450 enzymes is most likely to be inhibited by both diltiazem and verapamil and therebymincrease the risk for drug-drug interactions?

• A. CYP450 α2C9 (g%)
• B. CYP450 α2C19 (5%)
• C. CYP450 α2D6 (10%)
• D. CYP450 3A4 (77%)

• It is well known that both of these drugs can mediated drug interactions of substrates of CYP450 3A4 due to their inhibition of the enzyme.
• While they may inhibit the activity of some of the other CYP450 enzymes, the 3A4 enzyme is most likely to result in clinically relevant drug-drug interactions with medications who are to be substrates for CYP450 3A4.
• This is likely to be more so with verapamil.
• They can also cause drug interactions via their ability to inhibit the efflux cell transporter. MDR1 or P-gp.

34. Which of the following drug characteristics is known to influence the mechanism and degree of absorption from the gastrointestinal tract?

• A. Degree of lipophilicity of the drug (83%)
• B. Drug name and manufacturer (1%)
• C. Number of hydrogen bonds (14%)
• D. Shape of the tablet or capsule (1%)

• For a drug to be "lipophilic," it is "lipid" or "fat-loving" and generally opposes water or hydrophilic environments. The degree of lipophilicity directly impacts the ability of that medication to penetrate through a lipid cell membrane. A more lipophilic drug will more likely be able to go through a cell membrane (lipid bilayer) for absorption, especially if moving down a concentration gradient.
• Other important factors that can influence the medication's absorption is the degree of ionization (or charge) it carries. Regardless, if it has positive or negative charges as part of its structure, the more charges on the molecule, the less lipophilic it becomes. The presence of an electrical charge on the drug molecule is also influenced by the pH of the environment it is in (e.g., stomach versus small intestine versus in the bloodstream).
• All of these factors can contribute in the overall absorption process.
• Lipophilic or hydrophobic medications are more likely to cross through cell membranes which are made up of lipids, thereby influencing their distribution into certain tissues.

• Medications that are lipophilic or hydrophobic tend to have larger volumes of distribution (Vd).

35. Which of these chemotherapeutic drugs do not require dose reduction if the creatinine clearance is less than 25 ml/min?

• A. Bleomycin (16%)
• B. Doxorubicin (51%)
• C. Topotecan (15%)
• D. Pemetrexed (18%)

• The majority of doxorubicin is eliminated in the feces unchanged and only 5% is excreted in the kidneys.
• This pharmacokinetic characteristic allows for no renal dose adjustments in renal impairment.

37. Which of the following best describes pharmacokinetics? (Select all that apply)

• A. The study of pharmacology that is involved in determining the binding affinity for a given pharmacologic response seen in patients (10%)
• B. Determines the half-life (t1/2), volume of distribution (Vd), degree of protein binding for a drug (38%)
• C. Determines the effective dose for which 50% of the desired pharmacologic response (i.e. ED50) (13%)
• D. The study of pharmacology that describes the movement of drug throughout the body (40%)

• Pharmacokinetics is the area of pharmacology involved in the “movement” of the drug throughout the body and characterizes components of absorption, distribution, metabolism, and elimination (ADME). This pertains to the last answer choice, which is correct.
• Individual drug characteristics described in the study of pharmacokinetics include bioavailability, half-life, duration of action, degree of protein binding, the volume of distribution, degree of renal and hepatic elimination. This pertains to the second answer choice, which is correct.
• Pharmacodynamics is the area of pharmacology involved in determining the “effect” on the body (i.e., the “biologic or pharmacologic” response). This pertains to the first and third answer choices.
• The binding affinity is a parameter evaluated in the study of the pharmacodynamics of a medication and is reflective of how “tight” or the “strength of relationship” between the drug molecule and its receptor. The “potency” of a medication depends on both its receptor binding affinity and the degree of efficacy manifested. This is commonly referred to as the ED50 (effective dose) or EC50 (effective concentration) where 50% of the desired biologic or pharmacologic response is generated in the body. This pertains to the third answer choice.
• Pharmacokinetics is the area of pharmacology involved in the ‘movement’ of drug throughout the body, whereas pharmacodynamics is the area of pharmacology involved in the study of the ‘effect’ on the body (i.e., the ‘biologic or pharmacologic’ response).
• The bioavailability is related to the amount of drug that makes it into the central or systemic circulation compared to the amount administered.
• Medications administered by IV infusion or IV push have a 100% bioavailability because all the medication administered is directly put into central or systemic circulation (i.e., none of the drug is lost from the patient’s mass metabolism by the liver or eliminated in the stool before making it into the portal circulation).

38. Since the first TKI was approved in 2001, many TKIs have been approved for the treatment of various cancers. Each of these TKIs has a unique toxicity profile compared to conventional chemotherapy. Which of the following TKIs is correctly paired with its corresponding monitoring parameters?

• A. Sorafenib blood pressure, skin, amylase/lipase (45%)
• B. Lapatinib ECHO, creatinine, skin (19%)
• C. Ruxolitinib CBC, cholesterol, TSH (15%)
• D. Dasatinib CBC, cholesterol, fluid retention (21%)

• The first answer choice is correct. Sorafenib is associated with hypertension, hand-foot syndrome, and increased amylase/lipase.
• Lapatinib (second answer choice) is associated with a decreased left ventricular ejection fraction and hand-foot syndrome when given with capecitabine but is minimally renally eliminated.
• Ruxolitinib (third answer choice) is associated with myelosuppression and hyperlipidemia but not hypothyroidism.
• Dasatinib (last answer choice) is associated with myelosuppression and pleural effusions but not hyperlipidemia.
• Each TKI has a unique toxicity profile depending on the receptors it targets.
• While each TKI has its own set of unique side effects, the majority of TKIs are associated with myelosuppression, nausea/vomiting, and diarrhea.

39. Which drug listed below is well known for causing pulmonary toxicity?

A. Bleomycin (88%)
B. Etoposide (4%)
C. Doxorubicin (6%)
D. Topotecan (2%)

41. Which of the following monoclonal antibodies is matched with its corresponding target and black-boxed warning?

• A Bevacizumab: VEGF, nephrotoxicity (19%)
• B Brentuximab vedotin: CD20, progressive multifocal leukoencephalopathy (PML) (20%)
• C Pertuzumab: HER2, pneumonitis (18%)
• D Eculizumab: complement protein C5, meningococcal infections (43%)

• Eculizumab is a monoclonal antibody that binds to complement protein C5, it has a black boxed warning of life-threatening meningococcal infections for which patients should either receive prophylaxis with vaccines or antibiotics.
• Although bevacizumab binds to VEGF, its black-boxed warnings are for GI perforation and severe or fatal hemorrhage.
• Although brentuximab vedotin has a black boxed warning for PML, its target is CD30.
• Although pertuzumab targets HER2, its black boxed warning is for cardiac failure decreased LVEF.
• Eculizumab is a monoclonal antibody that binds to complement protein C5. Patients should be counseled on the risk of serious meningococcal infections and receive prophylaxis with vaccines or antibiotics.
• Due to the risk of meningococcal infections, eculizumab is available only through a REMS program.

42.0True or False. The lower the therapeutic index (TI), the safer the medication and least likely it is considered a "narrow therapeutic index" drug.

A True (9%)
B False (91%)

• By definition, the larger the therapeutic index (TI), the safer the medication and least likely it will be labeled a narrow therapeutic index drug, as seen with medications such as lithium, digoxin, phenytoin, theophylline.
• The definition for the TI is - median toxic dose divided by the median effective dose.
• Therefore, the larger the dose required in order to be lethal, the larger the TI will become assuming the median effective dose does not also change.
• A large therapeutic index (TI) is always desired for any medication because it offers the greatest degree of safety for potential medication dosing errors. The larger the TI, the better as it relates to safety.

45. You are learning about the pharmacology of various chemotherapy agents, such as cell cycle-specific chemotherapy agents. Which of the below are considered cell cycle-specific?

• A Busulfan, cyclophosphamide, vincristine (19%)
• B Docetaxel, melphalan, dacarbazine (10%)
• C Paclitaxel, vinblastine, cytarabine (60%)
• D Busulfan, docetaxel, cytarabine (12%)

• The cell cycle has Go, G1, S, G2, and M phases, where various cell activities are ongoing, including protein synthesis, DNA synthesis, mitosis, etc.Answer is correct as paclitaxel, vinblastine, and cytarabine are all cell cycle-specific. These agents may induce their anti-cancer effects only in one of the phases of the cancer cycles. For instance, vinca alkaloids and taxanes work in the M phase, whereas antimetabolites interfere in the S phase.
• Cell cycle non-specific agents act independently of the cell cycle phases. Alkylating agents such as cyclophosphamide, meiphalan, dacarbazine, busulfan are cell cycle non-specific.
• Cell cycle-specific agents include the antimetabolites, vinca alkaloids, taxanes, and epipodophyllotoxins whereas the alkylating agents are cell cycle non-specific.
• Etoposide is cell cycle-specific and acts both in the M and S phases.

What efflux cell membrane transporter or pump does cyclosporine utilize in its elimination from the cell?

• A. P-glycoprotein (8%)
• B. MRP1 (5%)
• C. OATP1B1 (7%)
• D. OATP1B3 (3%)

Cyclosporine's metabolism is dependent on the presence and function of the cytochrome P450 (CYP) 3A4 enzyme, which means cyclosporine is a substrate CYP3A4. Furthermore, cyclosporine's elimination from cells and ultimately from the body is partially mediated by P-glycoprotein (Pgp), making it also a substrate for Pgp. For purposes of being complete, cyclosporine is also a potent inhibitor of several influx cell membrane transporters (OATP1B1, OATP1B3, OATP2B1) as well as the efflux cell membrane transporters (MRP2 and P-gp). As such, it is evident why drug interactions between cyclosporine and other medications are not only complex but cannot be easily or fully explained by a simple comparison of the CYP450 enzyme pathways between two or more medications.

49. Tyrosine kinase inhibitors (TKIs) have changed the way we manage various cancers. They also possess unique side effects that differ compared with chemotherapy. Which of the following is a less likely side effect of multi-targeted TKIs compared with standard chemotherapy?

• A. Hypertension (12%)
• B. Hand-foot syndrome (19%)
• C. QT prolongation (13%)
• D. Myelosuppression (57%)

• The last answer option is correct. As TKIs have a unique side effect profile compared to standard chemotherapy, Myelosuppression can be seen with TKIs, but the incidence and severity are significantly less than with standard chemotherapy agents.
• Since TKIs are designed to inhibit the activity of specific molecules, patients receiving TKIs are more likely to have a hand-foot syndrome, hypertension, OTC prolongation, and many other non-hematologic toxicities (first, second, and third answer options).
• Compared to standard chemotherapy, TKIs are not as likely to cause myelosuppression. Instead, TKIs have a unique side effect profile that may include hand-foot syndrome, hypertension, OTC prolongation.
• A multi-targeted TKI such as sorafenib can potentially cause the hand-foot syndrome, hypertension, and QTc prolongation.

50. Non-steroidal anti-inflammatory drugs (NSAIDs) are known to be weak acids. Which of the following observations(s) is/are accurate as it relates to the pharmacokinetics of NSAIDs? (Select all that apply)

• When the pH = pKa of the drug, there is an equal amount of the drug in its ionized state (i.e., charged state) and non-ionized state (non-charged state). When the pH is raised above the pKa, the drug molecule shifts to being less non-ionized to a state of donating its proton (i.e., H-ion) and becoming more ionized. Therefore, taking NSAIDs with antacids can raise the pH above the pKa and will cause the NSAID to become more ionized or hydrophilic. This pertains to the third and last answer options.
• Charged or ionized drug molecules are more hydrophilic (i.e., water-loving) and get trapped in that environment since hydrophilic molecules are less likely to cross cell membranes made of a “lipid” bi-layer.
• Drugs that are acids or weak acids are more likely to bind to albumin; whereas more basic drugs are more likely to bind to the alpha-1 acid glycoprotein. This pertains to the first answer choice.
• Drugs that are weak acids are more likely to get trapped in basic or alkaline environments since the pH is above the pKa.
• Drugs in an ionized state are more hydrophilic and less likely to move across cell membranes.
• When taking an NSAID by mouth where the stomach is at its normal acidic pH, the NSAID will be in its non-ionized state making it more lipophilic which will facilitate topical gastritis since it can cross through cell membranes and once inside the cells the pH is more basic thereby causing H ions to release inside the cell (i.e., a condition called H-ion back diffusion). Taking an NSAID with food or an antacid can reduce this.

52. Which of the following agents are known to cross the blood brain barrier and have some activity for CNS malignancies?

• A. Oxaliplatin (11%)
• B. Carmustine (71%)
• C. Rituximab (8%)
• D. Paclitaxel (10%)

• Carmustine (BICNU, Gilade®) is an alkylating agent (Nintrosourea type) approved to be used in the treatment of a variety of brain tumors.
• It is able to cross the blood brain barrier very effectively and achieve concentrations in the cerebrospinal fluid (CSF) that are greater than 50% of concentrations found in the blood.
• It is also highly lipid soluble and thus has a large volume of distribution of 33 L/kg33L/kg.

53. Which of the following agents(s) is/are known to exhibit zero-order elimination kinetics, where the rate of elimination is independent of the drug concentration initially given? (Select all that apply)

• A. Aspirin (42%)
• B. Ethanol (41%)
• C. Gentamicin (10%)
• D. Meloxicam (7%)

While most approved medications on the market follow first-order elimination kinetics, ethanol, aspirin, higher doses of phenytoin, theophylline and warfarin are exceptions to the rule.

• A. Vd represents the free fraction of drug in the body (42%)
• B. Vd can be calculated by determining the amount of drug in the body divided by the amount of drug in the plasma (36%)
• C. Drugs with a large Vd tend to leave the plasma and bind to tissue (40%)
• D. The Vd of a drug indicates the type of tissue a drug distributes into (22%)

• The volume of distribution (Vd) for a drug refers to the amount of drug present in the entire body compared to the amount of drug present in the plasma. This pertains to the second answer option.
• Drugs with a large Vd tend to distribute more into the tissue, but the Vd does NOT tell you which type of tissue. All you know is that the drug is not in the plasma. This pertains to the third and last answer options.
• As a general rule, drugs that are more lipophilic (i.e., fat-loving or soluble) tend to have a larger Vd and distribute into the fat.
• Drugs with a small Vd tend to reside mainly in the plasma since most of them tend to be hydrophilic (i.e., water-loving). A good example of this is the aminoglycoside antibiotic, gentamicin.
• The first answer option is a distractor and is reflective of protein binding, where the free fraction is the only pharmacologically active form of the drug.
• The volume of distribution (Vd) for a drug refers to the amount of drug present in the entire body compared to the amount of drug present in the plasma, but knowing the Vd for a drug does not tell which tissue that drug distributes into.
• Benzodiazepines are lipophilic molecules with a very large Vd and are known to distribute into fat tissue.
• Digoxin has a very large Vd and is known to distribute into the muscle mainly and thus is a dosed based on lean body mass.

57. LT is a 59-year-old male who is diagnosed with metastatic lung cancer. Today he presents with the progression of his lung cancer on platinum-based combination chemotherapy. Oncology fellow would like to initiate this patient on erlotinib, but not sure of its mechanism. Which of the following is the best response to his question?

• A Erlotinib inhibits epidermal growth factors (EGFRs) activity by preventing phosphorylation of extracellular domain of epidermal growth factor receptor (EGFR) (33%)
• B Erlotinib inhibits EGFRs activity by preventing phosphorylation of intracellular domain of the EGFR (42%)
• C Erlotinib inhibits EGFRs activity by binding to EGF and therefore preventing EGF interaction with EGFR (7%)
• D Erlotinib inhibits EGFRs activity by binding to EGFR and therefore preventing EGF interaction with EGFR (48%)

• The second answer is the correct answer because erlotinib is a tyrosine kinase inhibitor. All tyrosine kinase inhibitors work intracellularly and prevent auto-phosphorylation of receptor and further signal transduction.
• There is no phosphorylation activity that occurs extracellularly (first answer option).
• There are monoclonal antibodies that may inhibit growth factor activities by binding to a ligand or growth factor, like bevacizumab (third answer option) or binding to the receptor on the extracellular domain, like cetuximab (last answer option).
• TKIs work intracellularly and inhibit auto-phosphorylation of the reception, preventing further signal transduction.
• Erlotinib, gefitinib, afatinib, and osimertinib are all TKIs that inhibit autophosphorylation of the intracellular domain of EGFR.

• A. Protect carmustine from light (4%)
• B. Carmustine should be transferred into a non-PVC container and tubing (3%)
• C. Infuse carmustine over 2 hours or longer (1%)
• D. All of the above (92%)

61. Which of the following characterize a medication with a desirable and safe therapeutic index (TI) that is less likely to cause toxicity if there is an accidental overdose? (Select all that apply)

• A. A medication with a long half-life in the body (3%)
• B. A medication with a large LD50 in comparison to the ED50 (41%)
• C. A medication with a TI that is large (48%)
• D. A medication that exhibits zero-order elimination kinetics (8%)

• Only the second and third answer choices describe a medication with a safe or desirable therapeutic index (TI).
• By definition, the TI is the LD5050/ED5050 for a medication. The LD5050 is the dose of drug concentration that is lethal in 50% of patients and the ED5050 is the dose or drug concentration that exerts the desired pharmacologic effect in a patient. Therefore, the larger the LD5050 compared to the ED5050 the safer the medication.
• The larger the TI the lower risk in lethal toxicity if there is an accidental or intentional overdose.
• Medications with small TIs are more likely to cause toxicity if used outside the normal dosing and are less forgiving if a mistake is made.
• Medications with long half-lives can create a challenge during an accidental overdose due to the maintained pharmacologic effects of the drug over time. However, long half-lives do not necessarily mean the medications are unsafe or have a small TI, because a safer and desirable TI involves the margin of difference between the LD5050 and ED5050. This pertains to the first answer choice.
• Medications that exhibit zero-order elimination kinetics generally have a less than desirable safety profile, which is in part why most FDA-approved medications exhibit first-order elimination kinetics. This pertains to the last answer choice.
• The therapeutic index (TI) is the LD50/ED50 for a medication, and the larger the LD50 compared to the ED50 the safer the medication.
• Medications with a TI > 10 are generally considered to have a safer profile.
• Lithium and digoxin are classically known to have a very small TI and thus are categorized as drugs having a "narrow therapeutic index".

62. Which of the following agents should be dose adjusted in a patient with severe hepatic impairment?

• A. Cyclophosphamide (19%)
• B. Oxaliplatin (12%)
• C. Vinorelbine (58%)
• D. Bleomycin (12%)

• Vinorelbine (Navelbine) is a vinca alkaloid antineoplastic agent commonly used for the treatment of non-small cell lung cancer and should be used with caution and at lower doses in patients with known hepatic insufficiency.
• There are dose adjustments based on the serum bilirubin level:
  • If the bilirubin is < 2, then give 100% of the daily dose.
  • If it is between 2.1 - 3.0, then give 50% of the dose.
  • Lastly, if it is > 3, then give only 25% of the dose.
• Failing to do so can further increase the risk for hematological and neurological toxicities already associated with vinorelbine.

63. Which of the following components listed below are not normally considered to be part of pharmacokinetics?

• A. Absorption or bioavailability (2%)
• B. Receptor binding affinity (96%)
• C. Distribution (1%)
• D. Elimination (1%)

• A You may administer either agent first (5%)
• B You should administer the fluorouracil first followed the next day by leucovorin (17%)
• C You should administer the fluorouracil first followed immediately by leucovorin (21%)
• D You should administer the leucovorin first followed by fluorouracil (57%)

• Leucovorin can increase reduced folate cellular levels and therefore increase the stability of a ternary complex formed from the association of 5-fluoro-2-deoxy-5’ monophosphate (FdUMP). thymidylate synthase (TS), and reduced folate.
• This ternary complex provides prolonged TS inhibition and greater cytotoxicity.

65. Which of the following is the primary target of cetuximab?

• A. EGFR (71%)
• B. TGF alpha (8%)
• C. KRAS (8%)
• D. VEGF (12%)

Panitumumab (Vectibix) and cetuximab (Erbitux) bind to the extracellular domain of epidermal growth factor receptor (EGFR) and prevent ligand binding and receptor activation.

66. If a patient develops Grade 3 or 4 pustular lesions from erlotinib (Tarceva), which option would be the most appropriate?

• A. Permanently discontinue erlotinib (29%)
• B. Oral or topical clindamycin plus topical moisturizers (64%)
• C. Diphenhydramine (5%)
• D. Benzoyl peroxide (3%)

• Epidermal growth factor receptor (EGFR) inhibitors typically cause dermatological adverse effects.
• Treatment of a rash such as the one in this case requires topical therapies and antibiotics for the pustular lesions.

68. Which of these drugs would likely require dose reduction in a patient with hepatic insufficiency?

• A. Vincristine (66%)
• B. Topotecan (13%)
• C. Cladribine (7%)
• D. Hydroxyurea (14%)

• Vincristine (Vincasar PFS) is a vinca alkaloid antineoplastic agent commonly used to treat ALL, brain tumors, Hodgkin lymphoma, Non-Hodgkin's lymphoma, Wilm's tumor, neuroblastoma, and rhabdomyosarcoma.
  • If the serum bilirubin is > 3 mg/dL then the dose should be ≤ 5% of the normal dose.
  • If the bilirubin is 3–5 mg/dL then give ≥ 25% of the normal dose and if > 5 mg/dL or AST is > 180, then avoid its use.
• Failing to do so may increase the risk for developing hepatic sinusoidal obstruction syndrome (SOS) or what was previously called veno-occlusive disease.
• Look for signs and symptoms of hepatic SOS. Increases in bilirubin levels > 1.4 mg/dL development of ascites, hepatomegaly, and/or upper abdominal pain.
• Of note, vincristine is also classically associated with neurotoxicity.

71. What is the mechanism of synergy that is produced when leucovorin and fluorouracil are given sequentially?

• A. Leucovorin rescues fluorouracil toxicities by supplying necessary cofactors that have been depleted by TS (thymidylate synthase) inhibition. (32%)
• B. A ternary complex is formed with reduced folates, 5-fluoro-2-deoxy-5'-monophosphate (FdUMP), and TS to provided protracted TS inhibition and toxicity (60%)
• C. A complex is formed with reduced folates. glycinamide ribonucleotide formyltransferase (GARFT), and TS to provided protracted GARFT inhibition and toxicity (5%)
• D. A ternary complex is formed with folic acid, 5-fluorouridine, 5'-triphosphate (FUTP), and TS to provided protracted TS inhibition and toxicity (13%)

• Leucovorin can increase reduced folate cellular levels and therefore increase the stability of a ternary complex formed from the association of 5-fluoro-2-deoxy-5 monophosphate (FdUMP). Thymidylate synthase (TS), and reduced folate.
• This ternary complex provides prolonged TS inhibition and greater cytotoxicity than fluorouracil alone.

72. Why does bleomycin cause pulmonary disease and also hyperpigmentation of the skin?

• A. The vasculature is unable to filter bleomycin as it travels through the lung and skin (16%)
• B. Bleomycin is metabolized by bleomycin hydrolase, which is present in low levels in the lung and skin (70%)
• C. Bleomycin mimics asbestos, which is toxic to the mesothelial and epithelial cells (13%)
• D. Bleomycin is not toxic to the lungs or skin (2%)

• Bleomycin undergoes detoxification by bleomycin hydrolase
• Theoretically if the skin and lung enzyme concentrations are absent or low, those tissues may be more susceptible to bleomycin toxicities.
• However, correlation of bleomycin hydrolase levels with tumor cell sensitivity has been thus far negative

73. Bendamustine structurally is a combination of which two antineoplastic classes?

• A. Platinum and nitrosourea (7%)
• B. Purine antimetabolite and alkylator (59%)
• C. Vinca alkaloid and taxane (5%)
• D. Nitrosourea and pyrimidine antimetabolite (29%)

74. Which of the following is accurate about the protein binding of drugs? (Select all that apply)

• A The most common carrier protein involved is albumin (41%)
• B Drugs that are bound can exert their pharmacologic effects on the cells (3%)
• C Drugs can be displaced from binding sites by other drugs (38%)
• D Drugs that are more basic tend to bind to alpha-1 acid glycoprotein (18%)

• Proteins found in the body that are involved in the binding of drugs include most commonly albumin, alpha-1 acid glycoprotein, and globulins.This pertains to the first answer option.
• Drugs that are acidic or neutral will tend to bind to albumin, whereas more basic drugs tend to bind to an alpha-1 acid glycoprotein. This pertains to the last answer option.
• Only drugs that are in the “unbound” state (or “free-fraction”) can bind to target receptors on cells to exert their pharmacologic effects on the body. This pertains to the second answer option.
• One type of drug-drug interaction that can occur includes protein binding displacement. This especially occurs when two highly protein-bound drugs are used together and share the same protein binding pattern. This pertains to the third answer option.
• The three main carrier proteins in the body for drugs include albumin, alpha-1 acid glycoprotein, and globulins, and only a free or unbound drug can exert its pharmacologic effects.
• Examples of basic drugs that have significant binding to alpha-1 acid glycoprotein include: amitriptyline, metoclopramide, nicardipine, prednisolone, nortriptyline, propranolol, and verapamil.

75. Which of the following is NOT a side effect of nilotinib (Tasigna)?

A Fluid retention (13%)
B QTc prolongation (7%)
C Pancreatitis and elevated serum lipase (14%)
D Nephrotoxicity (66%)

76. Which of the following is accurate about the therapeutic index (TI) of a medication?

A. A larger TI is safer than a smaller TI (94%)
B. A smaller TI is safer than a larger TI (3%)
C. Medications with a long-half have a TI that is considered less desirable (2%)
D. Drugs with a large volume of distribution (Vd) generally have a less desirable TI (2%)

• The first answer is the only correct answer because it is simply the definition of the therapeutic index (TI), which is the LD₅₀/ED₅₀ for a medication.
• The larger the LD₅₀ compared to the ED₅₀, the safer the medication.
• A smaller TI is considered a medication with a “narrow therapeutic index”, which is known to be less desirable. This pertains to the second answer choice.
• Medications with long half-lives or large volumes of distribution do not necessarily mean they are unsafe or have a small TI; because a safer and desirable TI involves the margin of difference between the LD₅₀ and ED₅₀. The further apart these two values are, generally, the safer the medication. This pertains to the third and last answer choices.
• The therapeutic index (TI) is the LD₅₀/ED₅₀ for a medication, and the larger the LD₅₀ compared to the ED₅₀, the safer the medication.
• Medications with a TI > 10 are generally considered to have a safer profile.

81. What is the main method of carboplatin elimination from the body?

• A. Renal (86%)
• B. Hepatic (8%)
• C. Feces (4%)
• D. Hydrolysis (2%)

• About 70% of the administered carboplatin will be excreted unchanged in the urine over a period of 24 hours. As such, it needs to be dose adjusted for impaired renal function (i.e., creatinine clearance [CrCl] or glomerular filtration rate [GFR]).
• In fact, carboplatin is the only chemotherapy agent dosed using the Calvert formula, which takes into account renal function. The Calvert formula is dose mg = AUC × (GFR + 25). AUC = area under the curve.
• The FDA recommends using a glomerular filtration rate (GFR) of no more than 125 mL/min to avoid overdosing the carboplatin and causing toxicity. Typical carboplatin AUC ranges from 3–7 mg/mL/min.

82. Four different orally delivered medications were administered to a patient on four separate occasions in order to determine which of the four had the greatest degree of absorption or bioavailability. Based on the following F-values, which of the four drugs had the greatest degree of absorption or bioavailability?

A Drug A (F = 0.35) (1%)
B Drug B (F = 0.55) (87%)
C Drug C (F = 0.10) (9%)
D Drug D (F = 0.48) (2%)

The F-value is a "fraction" of the amount of drug administered that actually made it into blood or central circulation. The larger the F-value, the greater the percentage of drug administered was absorbed, and that makes it into the central blood circulation.

83. What common adverse effect from EGFR inhibitors can predict an increase in response rate and survival?

A. Anemia (15%)
B. Interstitial lung disease (6%)
C. Rash (74%)
D. Diarrhea (6%)

EGFR inhibitors like erlotinib can produce an impressive acneiform rash that may correlate with response and survival for various tumors.
If a patient presents with a non-threatening rash, clinicians typically treat through the rash to ensure the patient continues to receive the drug.
Severe life-threatening rashes will require temporary or permanent cessation of therapy.

87. Which protein in the body do many medications bind to for transport in the blood?

A Alpha-1 antitrypsin (2%)
B Amyloid (1%)
C Albumin (92%)
D Alpha-1 acid glycoprotein (6%)

Albumin is the main carrier protein for many medications in the body. The recognition of albumin's influence on drug binding is of clinical relevance for a number of medications. When medications are bound to albumin, they are not free (or unbounded) to then interact with the desired target (receptor, enzyme, gene, etc.). Said another way, only free or unbounded medication exerts a pharmacological or biological effect in the patient. In addition, the concentration of albumin in the body can also influence the concentration of the free or unbounded drug. For example, a medication with high protein (or albumin) binding in the presence of a low albumin concentration will generally mean that there will be a greater free fraction available to exert a pharmacological effect. This can be good or bad. Having too much free or unbounded drug can result in an exaggerated pharmacological effect that may manifest as an adverse drug reaction or side effect. A classic example of this situation is the use of phenytoin (Dilantin) for the treatment of epilepsy. Standard doses used in a patient with low albumin levels can increase its free fraction and, thus, cause Dilantin toxicity. Some drugs depend on the presence of albumin for its pharmacokinetic profile, such as insulin detemir (Levemir) used for the management of diabetes mellitus.
While alpha-1 acid glycoprotein is also a carrier of some medications, albumin is well known to be the major carrier. Amyloid is an abnormal sheet of protein that is associated with a number of disorders to organs, i.e., not a plasma protein. Alpha-1 antitrypsin is made in the liver but is used in the alveoli to prevent that overactivation of local trypsin that can breakdown local tissue (a deficiency of this is associated with pancreatic emphysema).

90. The following precautions and warnings are listed in the bevacizumab prescribing information. Which one does not require permanent discontinuation of the drug if this adverse effect should occur?

A Non-gastrointestinal fistula formation (8%)
B Myocardial infarction (4%)
C Proteinuria (6%)
D Nephrotic syndrome (4%)
E Reversible posterior leukoencephalopathy syndrome (16%)

Proteinuria occurs in approximately 20% of patients, whereas nephrotic syndrome in <1% of bevacizumab patients.
If ≥2 protein found on urinalysis, a 24-hour urine collection should be conducted.
If ≥2 grams of protein/24 hours is detected, bevacizumab is held until the urine protein is <2 grams/24 hours.
Presence of nephrotic syndrome necessitates permanent discontinuation of bevacizumab.

93. A new medication is being investigated to treat hyperuricemia in adult patients and was evaluated in normal healthy adult patients without hyperuricemia. In this study, the patients were given 250 mg by intravenous infusion over 5 minutes. The drug concentrations were then measured and plotted over a period of time until the drug was eliminated completely from the body. The researchers found that the new drug exhibited first-order elimination kinetics. Which of the following is/are correct about this new drug? (Select all that apply)

A The rate of elimination is independent of the drug concentration in the body (12%)
B After 2 half-lives of the drug, approximately 75% of the drug originally administered has been eliminated (3%)
C The amount of drug eliminated is the same per hour over the entire time frame (12%)
D The rate of elimination is dependent on the drug concentration present in the body (37%)

Both the second and fourth answer choices are correct and simply describe the main concepts of first-order elimination kinetics.
For drugs following first-order elimination kinetics, the drug concentration is reduced by 50% or one-half over each half-life (i.e., in the 1ˢᵗ half-life = 50% of the original dose is gone, and after the 2ⁿᵈ half-life=75% of the original dose is now gone from the body; or 25% of the original dose remains).
The other two answers (first and third options) say the exact same thing and reflect a drug exhibiting zero-order elimination kinetics.
Drugs that follow first-order elimination kinetics have a rate of elimination that is "DEPENDENT" on the drug concentration (i.e., the more drug you give the patient, the more that will be eliminated per hour), whereas a drug that exhibits zero-order elimination kinetics will eliminate only a set amount of drug per hour and is "INDEPENDENT" of the drug concentration.
Over 95% of the drugs currently used on the market follow first-order elimination kinetics.
Drugs like aspirin, ethanol, and higher doses of phenytoin follow zero-order elimination kinetics.

99. What laboratory value(s) should be monitored while receiving panitumumab?

A Complete blood counts (CBC) (21%)
B CBC and urinary protein (14%)
C Magnesium (60%)
D Liver function tests (14%)

Since panitumumab is a targeted agent towards EGFR, it does not directly cause blood count disruptions.
The only abnormality that has been noted is approximately 30% will develop hypomagnesemia, however, 7% developed significant hypomagnesemia.
Some patients will develop both hypomagnesemia and hypocalcemia.

103. According to the prescribing information, which one of the following oral chemotherapy agents requires the patient to take with food?

A. Capecitabine (66%)
B. Erlotinib (20%)
C. Hydroxyurea (14%)
D. Lapatinib (10%)

According to the package insert, capecitabine (Xeloda) should be administered within 30 minutes after a meal.
Lapatinib (Tykerb) and erlotinib (Tarceva) are recommended to be taken on an empty stomach, but its absorption is significantly enhanced when taken with food.
There is no recommendation for hydroxyurea in its prescribing information.

104. The creatine clearance is an estimation for which of the following physiologic parameters that is also known to influence drug elimination?

A Hepatic extraction (2%)
B Intestinal absorption of protein (1%)
C Glomerular filtration rate (97%)
D Biliary excretion rate (1%)

Creatinine is a byproduct of muscle metabolism, 90% of which is filtered into the bowman's space in the glomerulus. The other 10% is secreted into the renal tubule at the level of the proximal segment. As such, it is an estimate of the glomerular filtration rate (GFR) even though it does slightly overestimate the GFR due to secretion. Clinically, the creatinine clearance has been used for determining dose adjustments in medications more dependent on renal function for elimination, whereas the GFR is used for staging patients with chronic kidney disease (CKD) or chronic renal failure (CRF) - see figure below. Sometimes the creatinine clearance is similar or the same as the GFR (depending on the calculation used). For a comprehensive medical calculator for renal function, go to Pharmacology Weekly.
The hepatic extraction ratio does influence drug elimination but is not related to the creatinine clearance. The others are distractors are less related.

105. Besides neutropenia, what is the other dose-limiting toxicity of paclitaxel?

A. Stomatitis (8%)
B. Neuropathy (81%)
C. Palmar-plantar erythrodysesthesia (8%)
D. Ataxia (3%)

Paclitaxel is a microtubule-stabilizing agent that produces peripheral neuropathy as a major adverse event.
Paclitaxel binding of the microtubular polymer can lead to axonal degeneration, especially with larger doses greater than 200 mg/m² or with cumulative exposure.

110. Which of the following types of thrombocytopenia related to heparin use is characterized as occurring after 4 days of heparin therapy?

A. Heparin associated thrombocytopenia (10%)
B. Heparin Induced thrombocytopenia (84%)
C. Type I Heparin linked thrombocytopenia (2%)
D. Non-immune mediated heparin associated thrombocytopenia (4%)

The two main categories are non-immune and immune-mediated thrombocytopaenia.
Non-immune-mediated is now generally referred to as heparin-associated thrombocytopenia (HAT), but in the past had also been called type I HIT. In short, the reduction in platelet counts generally do not fall below 100,000/mm33 (or result in reductions in platelet counts beyond 30–50%) and are not associated with the formation of IgG antibodies or thrombus formation. This small decrease in platelet count also typically occurs earlier than in HIT and generally returns to baseline within a few days of heparin discontinuation.
This is different from the immune-mediated type or HIT, which is associated with platelet reductions of >30–50% and, in many cases, is also associated with the development of potentially life-threatening thrombosis formation. Heparin-induced thrombocytopenia is also different from HAT in that the typical onset of platelet reductions occur after 4 days of heparin or low-molecular-weight heparin (LMWH) therapy, versus within 48–72 hours for HAT. This type of HIT has been traditionally called type II HIT. To confuse matters slightly more, some literature and regulatory agencies also call it heparin-induced thrombocytopenia & thrombosis (HITT).

112. Which type of medication dosage formulation almost always has a bioavailability of 100% or a F-value of 1.0?
A Tablet (1%)
B Capsule (1%)
C Intravenous (98%)
D Transdermal (1%)
[expand] Answer (C)

While a tablet and even a capsule can get very close to a 100% bioavailability, these dosage forms 'generally' do not and vary from one medication to another. However, giving a medication directly into the systemic (or central circulation) implies a 100% bioavailability. Furthermore, intravenous (IV) delivery also bypasses first-pass metabolism by the liver that normally occurs with oral administration of a medication.

113. Which tyrosine kinase inhibitor prevents the formation of the fusion oncogene EML4-ALK?
A. Crizotinib (Xalkori) (60%)
B. Dasatinib (Sprycel) (20%)
C. Vandetanib (Caprelsa) (11%)
D. Vemurafenib (Zelboraf) (9%)

Crizotinib is a tyrosine kinase inhibitor (TKI) for locally advanced or metastatic non-small cell lung cancer that possesses an ALK (anaplastic lymphoma kinase) mutation.
By blocking the phosphorylation of ALK, this will not allow the fusion protein to be developed and will, therefore, allow apoptosis.
The brand name, Xalkori, has the letters ALK to allow for easy recognition.

118. Which monoclonal antibody is conjugated with a toxin?

A Alemtuzumab (Campath) (18%)
B Brentuximab (Adcetris) (58%)
C Ofatumumab (Arzerra) (10%)
D Ipilimumab (Yervoy) (14%)
[expand] Answer (B)

Brentuximab is combined with vedotin or monomethyl auristatin E, a microtubule disrupting agent causing cell cycle arrest and apoptosis.
Brentuximab is a monoclonal antibody designed to bind with CD30 positive cells.
Brentuximab vedotin is an antibody-drug conjugate (ADC), which "ADC" is found within the brand name, Adcetris.

128. A patient has been taking Drug A for six months with a good response to hypertension treatment. This patient is then started on a Drug B for a viral infection, and now the patient is reporting that his blood pressure is not as controlled despite his doctor increasing the dose of Drug A. Which of the following best describes this drug interaction?

Labels:

A Drug B is likely an irreversible antagonist that is causing a non-competitive interaction (4%)
B Drug B's metabolism is affected by the presence of a genetic polymorphism that is causing a competitive interaction (4%)
C Drug B is likely competing with Drug A for the same receptor binding site (4%)
D The use of Drug B is requiring a smaller dose of Drug A to achieve the same efficacy (2%)
[expand] Answer (A)
Only the first answer choice is correct. The use of Drug B in this patient is causing an irreversible drug interaction with Drug A, thereby causing a reduction in the maximal pharmacologic response that could be achieved with Drug A at a particular drug concentration. As such, Drug B is acting as an antagonist with irreversible activity on the target receptor used by Drug A.
A shift to the right in the dose-response curve (not pictured above) is classically seen in patients experiencing a competitive drug-drug interaction where both Drug A and Drug B are trying to compete for the same receptor binding site. This pertains to the third answer choice.
While Drug B's metabolism could be influenced by the presence of genetic polymorphism, that is not what is being displayed here in this dose-response curve. The second answer choice is a distractor.
The last answer choice is not correct by simply looking at the graph; which shows that the drug concentration (i.e., amount of drug provided by a particular dose) is not changing, but rather the degree of pharmacologic response exhibited.
A drug that functions as an irreversible antagonist non-competitively inhibits the activity of another drug, thereby resulting in a reduced pharmacologic response.
Irreversible antagonists typically result in a non-competitive interaction with an agonist on the same target receptor.

130. Which of the following designations in the name of a monoclonal antibody describes it to be a humanized monoclonal IgG antibody?
A -umab (44%)
B -ximab (6%)
C -omab (2%)
D -zumab (48%)

Naming set by the International Nonproprietary Names (INN) by the World Health Organization (WHO):
Drug Name organization:
Prefix-substem A-substem B-suffix
Prefix per manufacturer
Substem A - target class
Substem B - species mAb derived
Suffix (or stem) = -mab

132. Which of the targeted agents has the potential to produce interstitial lung disease?

A. Erlotinib, pazopanib, vemurafenib (20%)
B. Vandetanib, lapatinib, cetuximab (24%)
C. Imatinib, dasatinib, nilotinib (29%)
D. Bevacizumab, sunitinib, sorafenib (27%)

Tyrosine Kinase Inhibitors Primary Targets EGFR Monoclonal Antibodies
Gefitinib (Iressa) EGFR Cetuximab (Erbitux)
Erlotinib (Tarceva) EGFR Panitumumab (Vectibix)
Lapatinib (Tykerb) EGFR HER2
Vandetanib (Caprelsa) EGFR VEGFR

Any agent that possesses activity against EGFR (epidermal growth factor receptor) will have a warning for the pulmonary toxicity, interstitial lung disease (ILD). The ILD incidence with gefitinib and erlotinib in lung cancer patients has been reported to be as high as 8% in Japanese patients than <1% in the rest of the world. It is theorized that EGFR signaling may be responsible for the repair of the damaged lung tissue. Therefore, using EGFR inhibitors may negatively affect the pneumocyte's ability to respond to lung injury leading to ILD and pulmonary fibrosis. The ILD risk factors were evaluated in Japanese patients receiving erlotinib or gefitinib. From a multivariate analysis, poor performance status and previous pulmonary fibrosis were the two main risk factors.

134. DS is a 68-year-old with non-small lung cancer who presents to his oncologist with complaints of heartburn and stomach pains. He denies any black or bloody stools and does not have any nausea or vomiting. He is currently receiving erlotinib therapy. He has stable pain, which is controlled with nonsteroidal anti-inflammatory drugs (NSAID) along with morphine. Which agent would be the most appropriate therapy for his suspected NSAID induced gastritis?

A. Stop NSAIDs and begin aluminum hydroxide / magnesium hydroxide (65%)
B. Stop NSAIDs and begin cimetidine (8%)
C. Continue NSAIDs and start ranitidine (11%)
D. Continue NSAIDs and start omeprazole (26%)

Stopping NSAIDs will be the most appropriate initial therapy for DS.
PPIs or H2 blockers will be more effective than antacids for gastritis but will potentially decrease the pH-dependent absorption of erlotinib.
Antacids do not significantly alter gastric pH, so that this interaction will be unlikely.
Some data claims that separating the H2 blockers from the erlotinib dose will minimize this interaction. The package insert for erlotinib recommends giving erlotinib 10 hours after the H2 blocker and at least 2 hours before the next dose of the H2 blocker. Cimetidine could be administered in that fashion but is not desirable because of a drug interaction.
Cimetidine is an inhibitor of cytochrome P450 3A4 which is required for erlotinib metabolism.

136. True or False:

The creatinine clearance can be calculated in both pediatric and adult patients by using the Cockcroft-Gault equation.

A True (16%)
B False (84%)

The use of the Cockcroft-Gault equation is only applicable for patients over 18 years of age.
This equation was validated and studied primarily in adult men and, therefore, does not apply to children.
The Schwartz and Traub methods have been used to estimate the glomerular filtration rate in children < 18 years of age.
When in doubt, a 24-hour urine collection can be useful for pediatric patients but is cumbersome and time consuming in certain situations.

37. The oncologist plans to start a patient on paclitaxel and carboplatin for NSCLC if the target AUC is 6 and the patient has a GFR of 75. what is the dose of carboplatin this patient should receive?

A 400 mg (6%)
B 500 mg (6%)
C 600 mg (86%)
D 700 mg (2%)

Although the specific formula used for this calculation is not explicitly detailed in the provided sources, the sources consistently identify AUC 6 as the target for the carboplatin and paclitaxel regimen used in treating Non-Small Cell Lung Cancer (NSCLC).

In clinical practice, carboplatin dosing is determined using the Calvert formula, which is calculated as follows (please note this formula is not in your provided sources and should be independently verified):

Total Dose (mg) = Target AUC × (GFR + 25)

Applying the values from your query:

Target AUC = 6
GFR = 75
Calculation: 6 × (75 + 25) = 6 × 100 = 600 mg

138. Ifosfamide's metabolite, chloroacetaldehyde, has been implemented in causing which toxicity?
A. Neurotoxicity (65%)
B. Thrombocytopenia (14%)
C. Cardiomyopathy (13%)
D. Tinnitus (7%)

140. Which of the following is a known pathway of Phase I drug metabolism?

A N-acetyltransferase (6%)
B UGT1A4 (6%)
C Glutathione conjugation (11%)
D CYP450 2C9 (78%)

The only answer choice listed that contributes to phase I is the CYP450 cytochrome P450 monooxygenase system or also known as cytochrome P-450-dependent mixed-function oxidase system which are involved in oxidation, reduction or hydrolysis of drugs which can generate drug metabolites that are more active than the parent drug, active or inactive.
UGT (also referred to as the enzymes UDP-glucuronyltransferase), N-acetyltransferase and glutathione conjugation are all pathways of Phase II drug metabolism.
Phase II pathways of metabolism generally make the drug metabolite less active or inactive through conjugation reactions that make the drug metabolite charged and more hydrophilic for improved renal elimination. Commonly charged conjugates added include glutathione, glucuronic acid, glycine, or sulfate.
Pathways involved in phase I drug metabolism include oxidation, reduction, and hydrolysis enzymes. With the CYP450 enzymes being a primary contributor.
The most common pathway of Phase I metabolism involved in drug metabolism is the CYP450 3A4 enzyme.

141. What physiological process that influences drug elimination can significantly decrease as the patient ages and thus, have a direct impact on drug dosing?

A. Renal function (glomerular filtration rate) (91%)
B. Gastric emptying (2%)
C. Skin thickness (1%)
D. Forced expiratory volume (FEV) (1%)

It is well known that all elderly patients (> 50 yrs) start to lose renal function. The average loss in glomerular filtration rate (GFR) is about 1% per year over 50. Since many medications are renally eliminated, the calculation of the creatinine clearance (CrCl) is very important to the appropriate dosing and use of medications. It is also important to know that it is "normal" for older patients to have a low GFR when compared to a younger person. If the rate is greater than 1% per year then an underlying kidney problem is likely present.
For a comprehensive medical calculator that assess renal function, go to Pharmacology Weekly.

142. What is the biologic target of cetuximab?

A EGFR (71%)
B TGF alpha (8%)
C KRAS (9%)
D VEGF (13%)

Pantumumab (Vectibix) and cetuximab (Erbitux) are monoclonal antibodies for 'mabs' that bind to the extracellular domain of endothelial growth factor receptor (EGFR) and thereby prevent ligand binding and receptor activation.
Pantumumab differs from cetuximab because it is a 100% human antibody, whereas cetuximab is a chimeric antibody (67% human and 33% mouse).
Both agents are used in the treatment of colorectal cancer. Cetuximab is also used for lung cancer.