Chemotherapy Drugs: The Ultimate Guide to Anticancer Drug Classifications, Master This High-Yield Topic for GPAT and NIPER.

Chemotherapy Drugs: The Ultimate Guide to Anticancer Drug Classifications, Master This High-Yield Topic for GPAT and NIPER.

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Chemotherapy is a broad term. For exams like GPAT and NIPER, you score best when you can classify anticancer drugs by mechanism, cell-cycle specificity, and key toxicities. This guide gives you the structure, the “why” behind each class, and high‑yield associations that show up in questions.

How anticancer drugs are classified

  • By mechanism (most practical for exams): alkylators, antimetabolites, antitumor antibiotics, microtubule agents, topoisomerase inhibitors, hormonal agents, targeted therapies, and others (e.g., asparaginase, hydroxyurea).
  • By cell-cycle action: cell cycle–specific (CCS) vs cell cycle–nonspecific (CCNS). This explains schedule dependence and toxicity patterns.
  • By molecular target: kinase inhibitors (EGFR, BCR‑ABL), monoclonal antibodies (HER2, VEGF), immune checkpoint blockers (PD‑1, CTLA‑4).

Knowing why a drug works (its target) predicts both its benefits and its adverse effects. For example, EGFR inhibitors cause acneiform rash because EGFR is active in skin.

Cell cycle map you must know

  • CCS drugs:
    • S phase: methotrexate, 5‑FU, cytarabine, gemcitabine, 6‑MP, cladribine, hydroxyurea.
    • G2 phase: bleomycin.
    • M phase: vinca alkaloids (inhibit polymerization), taxanes (inhibit depolymerization).
  • CCNS drugs: alkylating agents (cyclophosphamide, cisplatin), anthracyclines (doxorubicin), dactinomycin. They hit DNA regardless of phase, so total dose matters more than schedule.

Why it matters: CCS drugs need dividing cells to work; they are schedule dependent and often cause mucositis and myelosuppression. CCNS drugs are more dose dependent and can work on slower tumors.

Major classes, prototypes, and what exams test

  • Alkylating agents (CCNS): add alkyl groups to DNA, crosslink strands, and trigger apoptosis. Fast-dividing tissues get hit first.
    • Nitrogen mustards: cyclophosphamide, ifosfamide. Key toxicity: hemorrhagic cystitis from acrolein. Prevent with MESNA and hydration. Ifosfamide can cause encephalopathy (chloracetaldehyde).
    • Nitrosoureas: carmustine, lomustine. Cross the BBB because they are lipophilic. Use in brain tumors. Delayed myelosuppression; carmustine can cause pulmonary fibrosis.
    • Alkyl sulfonate: busulfan. Myeloablation before transplant. Causes severe myelosuppression and “busulfan lung” (fibrosis).
    • Triazenes: dacarbazine, temozolomide. Methylate DNA. Temozolomide is oral and useful in gliomas. Myelosuppression and nausea are common.
    • Platinum compounds: cisplatin, carboplatin, oxaliplatin. Crosslink DNA like alkylators. Cisplatin causes nephrotoxicity and ototoxicity because proximal tubules and cochlear cells are sensitive to ROS. Prevent renal injury with saline diuresis and sometimes amifostine. Carboplatin: more myelosuppression, less renal/oto toxicity. Oxaliplatin: cold‑induced neuropathy and laryngopharyngeal spasm.
  • Antimetabolites (S phase): mimic nucleotides and block DNA synthesis.
    • Folate analogs: methotrexate (DHFR inhibitor), pemetrexed (multi‑TS/DHFR). MTX toxicity: myelosuppression, mucositis, hepatotoxicity, and crystalluria. Leucovorin rescues normal cells by bypassing DHFR. Alkalinize urine to prevent MTX precipitation.
    • Pyrimidine analogs: 5‑FU inhibits thymidylate synthase via FdUMP. Leucovorin enhances 5‑FU binding to TS (it is not a rescue here). Toxicities: diarrhea, mucositis, hand‑foot syndrome; severe toxicity with DPD deficiency. Cytarabine (ara‑C): chain termination; cerebellar toxicity and chemical conjunctivitis. Gemcitabine: broad use; myelosuppression and thrombocytopenia.
    • Purine analogs: 6‑MP, 6‑TG, cladribine, fludarabine. 6‑MP is metabolized by xanthine oxidase; reduce dose with allopurinol or febuxostat to avoid hepatotoxicity. Cladribine is resistant to ADA, so it kills lymphocytes (hairy cell leukemia). Fludarabine causes profound immunosuppression and neurotoxicity.
  • Antitumor antibiotics:
    • Anthracyclines: doxorubicin, daunorubicin. Intercalate DNA, inhibit topoisomerase II, and generate free radicals. Dose‑related dilated cardiomyopathy occurs because cardiac tissue has low antioxidant enzymes. Prevent with dexrazoxane. Vesicants; cause red‑orange urine.
    • Bleomycin (G2 specific): free radical DNA breaks. Minimal myelosuppression; instead causes pulmonary fibrosis and skin changes. Lungs are vulnerable due to low bleomycin hydrolase.
    • Dactinomycin: intercalates DNA; used in pediatric tumors (Wilms, rhabdomyosarcoma). Myelosuppression is dose‑limiting.
  • Microtubule agents (M phase):
    • Vinca alkaloids: vincristine, vinblastine, vinorelbine. Prevent tubulin polymerization. Neurons rely on microtubules for axonal transport, so vincristine causes neuropathy and autonomic ileus; relatively less myelosuppression. Vinblastine “blasts” the bone marrow.
    • Taxanes: paclitaxel, docetaxel, cabazitaxel. Stabilize microtubules; cells cannot complete mitosis, leading to apoptosis. Cause neuropathy, myelosuppression, and hypersensitivity (formulation solvents). Premedicate with steroids and antihistamines. Docetaxel causes fluid retention.
  • Topoisomerase inhibitors:
    • Topo I: irinotecan, topotecan. Irinotecan causes early cholinergic diarrhea (treat with atropine) and late secretory diarrhea (treat aggressively with loperamide). UGT1A1*28 polymorphism increases risk.
    • Topo II: etoposide, teniposide. Myelosuppression and risk of secondary AML with 11q23 translocations.
  • Hormonal and endocrine therapies:
    • SERMs: tamoxifen (ER antagonist in breast, agonist in endometrium and bone). Decreases breast cancer recurrence but increases risk of endometrial carcinoma and VTE; causes hot flashes.
    • Aromatase inhibitors: anastrozole, letrozole, exemestane. Lower estrogen in postmenopausal women; cause bone loss and arthralgia.
    • Androgen axis: leuprolide (GnRH agonist) + bicalutamide (antiandrogen) to block flare; or degarelix (GnRH antagonist). Expect hot flashes, metabolic effects, osteoporosis.
    • Glucocorticoids (e.g., prednisone): lympholytic, key in leukemias/lymphomas, and reduce chemo‑induced nausea; long‑term toxicities are typical Cushingoid features.
  • Targeted therapies and immunotherapy:
    • BCR‑ABL: imatinib, dasatinib, nilotinib. Inhibit the fusion kinase in CML. Toxicities: edema (imatinib), pleural effusions (dasatinib), QT prolongation (nilotinib).
    • EGFR TKIs: erlotinib, gefitinib, afatinib, osimertinib. Rash and diarrhea signal on‑target effect; interstitial lung disease can occur. Osimertinib hits T790M and can prolong QT.
    • ALK inhibitors: crizotinib, alectinib. Visual trails, bradycardia, myalgia; alectinib has better CNS penetration.
    • HER2 antibodies: trastuzumab, pertuzumab. Reversible cardiomyopathy because HER2 is involved in cardiomyocyte survival.
    • VEGF/VEGFR blockers: bevacizumab (mAb), sunitinib, sorafenib, pazopanib. Hypertension and proteinuria due to endothelial effects; impaired wound healing and bleeding with bevacizumab.
    • BRAF/MEK: vemurafenib, dabrafenib + trametinib. Cutaneous SCC, photosensitivity, fever.
    • Checkpoint inhibitors: ipilimumab (CTLA‑4), nivolumab/pembrolizumab (PD‑1), atezolizumab (PD‑L1). Remove immune brakes, so immune‑related adverse events occur: dermatitis, colitis, hepatitis, pneumonitis, and endocrinopathies (thyroiditis, hypophysitis). Treat moderate to severe cases with steroids.
  • Other high‑yield agents:
    • ATRA (tretinoin) and arsenic trioxide for APL (t(15;17)). Risk of differentiation syndrome: fever, pulmonary edema, hypotension; treat with steroids.
    • Hydroxyurea: inhibits ribonucleotide reductase; S phase. Increases HbF; used in myeloproliferative disorders and sickle cell disease. Myelosuppression, leg ulcers.
    • Proteasome inhibitors: bortezomib, carfilzomib in myeloma. Cause peripheral neuropathy (more with bortezomib) and herpes zoster reactivation (use antiviral prophylaxis).
    • IMiDs: thalidomide, lenalidomide. Antiangiogenic and immunomodulatory. Teratogenic; also neuropathy, constipation (thalidomide), and myelosuppression/VTE (lenalidomide).
    • L‑asparaginase/pegaspargase: depletes asparagine so leukemic lymphoblasts cannot synthesize protein. Causes pancreatitis, hyperglycemia, coagulopathy, and hypersensitivity.

Dose‑limiting toxicities and protective agents

  • Methotrexate: myelosuppression, mucositis, nephrotoxicity. Rescue with leucovorin; use hydration and urinary alkalinization. Glucarpidase clears MTX in renal failure.
  • 5‑FU/capecitabine: diarrhea, mucositis, hand‑foot. Severe toxicity in DPD deficiency. Uridine triacetate is an antidote for overdose/early severe toxicity.
  • Cisplatin: nephrotoxicity and ototoxicity. Prevent with saline diuresis; consider amifostine. Sodium thiosulfate can protect hearing in selected pediatric use.
  • Ifosfamide/cyclophosphamide: hemorrhagic cystitis. Prevent with MESNA + hydration.
  • Doxorubicin: cardiomyopathy. Limit cumulative dose; use dexrazoxane.
  • Vincristine: neuropathy and ileus. Keep dose low; avoid azole interactions that raise levels.
  • Bleomycin: pulmonary fibrosis. Monitor DLCO; avoid high oxygen exposure.
  • Irinotecan: diarrhea. Atropine for early; high‑dose loperamide for late.

Resistance mechanisms you should recognize

  • Increased drug efflux: P‑glycoprotein (MDR1) pumps out vincas, taxanes, and anthracyclines.
  • Target modification: topoisomerase mutations (etoposide), tubulin mutations (taxanes/vincas), kinase gatekeeper mutations (EGFR T790M, BCR‑ABL T315I).
  • Enhanced DNA repair: MGMT repairs alkylation (temozolomide resistance).
  • Metabolic changes: DPD deficiency increases 5‑FU toxicity; TPMT deficiency increases thiopurine toxicity; UGT1A1*28 increases irinotecan toxicity.

Why this is tested: resistance explains loss of response and guides next‑line therapy (e.g., osimertinib for EGFR T790M).

High‑yield quick checks

  • Vesicants: anthracyclines and vinca alkaloids. Extravasation causes tissue necrosis; manage with cold/warm compresses and specific antidotes (dexrazoxane for anthracyclines; hyaluronidase for vincas).
  • “Bleo lungs, not marrow”: bleomycin spares bone marrow but scars lungs.
  • “Vincristine = nerves; Vinblastine = bone marrow.”
  • Tamoxifen: reduces breast cancer recurrence but raises endometrial cancer and VTE risk due to partial agonism.
  • 5‑FU vs MTX and leucovorin: leucovorin enhances 5‑FU effect; it rescues from MTX.
  • Platinum triad: nephrotoxicity, ototoxicity, neuropathy (oxaliplatin gives cold neuropathy).
  • Brain tumors: choose nitrosoureas or temozolomide because they cross the BBB.
  • TLS risk drugs: steroids in leukemia, cytarabine, and rituximab can trigger tumor lysis.

Supportive care that saves lives (and marks)

  • Tumor lysis syndrome (TLS): prevent with hydration and allopurinol; treat high uric acid with rasburicase. TLS causes hyperkalemia, hyperphosphatemia, hypocalcemia, and AKI.
  • Antiemetics: use 5‑HT3 antagonists (ondansetron), NK1 antagonists (aprepitant), dexamethasone for highly emetogenic regimens like cisplatin.
  • Myelosuppression: give G‑CSF (filgrastim) for febrile neutropenia risk. Time your cycles based on neutrophil recovery because marrow is the dose‑limiting tissue for many drugs.
  • Infection and HBV reactivation: screen before rituximab and some TKIs. Prophylax as needed.
  • Osteoprotection: AIs and ADT cause bone loss; use calcium, vitamin D, and consider bisphosphonates or denosumab.

Applying the map: quick case picks

  • APL with t(15;17): choose ATRA ± arsenic; watch for differentiation syndrome.
  • HER2‑positive breast cancer: add trastuzumab; monitor LVEF.
  • EGFR‑mutant NSCLC: start an EGFR TKI (e.g., osimertinib if T790M). Expect rash and diarrhea.
  • Testicular cancer: BEP regimen (bleomycin, etoposide, cisplatin). Monitor lungs and kidneys.
  • Brain glioma: temozolomide; check MGMT methylation for sensitivity.

Master the classification, connect each mechanism to its signature toxicity, and remember the rescue agents. That logic will help you answer most GPAT/NIPER questions on chemotherapy drugs, even when the regimen names or cancer subtypes vary.

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