Click here for more detail — Anticancer drugs — definition
Anticancer drugs — definition
Anticancer drugs (antineoplastic, oncolytic, cytotoxic agents) selectively kill or arrest growth of malignant tumour cells. The fundamental challenge of cancer chemotherapy is selectivity: cancer cells share virtually all biochemistry with normal cells. The only exploitable differences are: (1) higher growth fraction (more cells in active cell cycle), (2) impaired DNA-damage repair, (3) lineage-specific antigens or hormone dependence in some tumours.
Hence most cytotoxic agents target rapidly dividing cells indiscriminately — both cancer and normal proliferating tissues — leading to predictable toxicity profile: bone marrow suppression (myelosuppression), mucositis (GI epithelium), alopecia (hair follicles), nausea + vomiting (CTZ + GI), reproductive (germ cells).
Three strategic eras: Cytotoxic era (1940s–2000): alkylating agents, antimetabolites, plant alkaloids, antibiotics. Targeted era (2000–2015): imatinib for CML, trastuzumab for HER2+ breast cancer, rituximab for B-cell lymphoma, kinase inhibitors. Immunotherapy era (2015–present): checkpoint inhibitors (nivolumab, pembrolizumab, ipilimumab), CAR-T cell therapy, bispecific antibodies.
Combination chemotherapy is standard practice — drugs from different classes with non-overlapping toxicities and different mechanisms reduce resistance and improve outcomes (CHOP, R-CHOP, FOLFOX, BEACOPP regimens).
Anticancer drugs selectively kill or arrest growth of malignant tumour cells. Cytotoxic agents target rapidly dividing cells (cancer + normal proliferating tissues → toxicity). Targeted therapy hits cancer-specific molecules (kinases, HER2, CD20, immune checkpoints). Combination regimens are standard.
Critical points: hydrate cisplatin patients · leucovorin rescue 24 h after high-dose MTX · doxorubicin lifetime cumulative dose 550 mg/m² (cardiotoxicity) · check TPMT genotype before 6-MP · pregnancy contraindicated for nearly all cytotoxics.
4. Mechanism of Action — Cell Cycle Phase Specificity
📖 Cell-cycle phase specificity — CCS drugs (S, G2, M phase) vs CCNS drugs (all phases incl. G0)
Cell cycle + drug phase specificity
Cell cycle phases.G0: resting / quiescent — most adult cells (most resistant to chemo). G1 (gap 1): cell grows; protein + organelle synthesis; 8–12 h. S (synthesis): DNA replication; 6–8 h. G2 (gap 2): cell prepares for mitosis; 2–6 h. M (mitosis): cell divides; ~1 h. Total cycle 18–24 h for typical tumour cells.
Cell-cycle phase-specific drugs (CCS). Active only in one specific phase. Most effective against rapidly proliferating tumours. Bone marrow toxicity is severe but often limited to one cell type. G1: asparaginase (depletes asparagine for protein synthesis). Corticosteroids (lympholytic in G1). S: antimetabolites — methotrexate, 5-FU, cytarabine, gemcitabine, hydroxyurea (block DNA synthesis only when cell is replicating). G2: bleomycin (G2-specific via free radicals), etoposide (topo II at late S/G2). M: vinca alkaloids (vincristine, vinblastine — bind tubulin, prevent polymerisation), taxanes (paclitaxel, docetaxel — stabilise microtubules, prevent depolymerisation).
Cell-cycle non-specific drugs (CCNS). Act in all phases including G0. Can hit slow-growing tumours. Alkylating agents: cyclophosphamide, cisplatin, busulfan, melphalan — covalent DNA crosslinks. Anthracyclines: doxorubicin, daunorubicin — DNA intercalation + topo II + free radicals. Hormonal agents: work in any phase by altering cellular environment.
Why phase specificity matters clinically. Phase-specific drugs are more effective when given as continuous infusion (cytarabine 5–7 day infusion in AML) or repeated low-dose regimens that catch more cells in the vulnerable phase. Non-specific drugs can be given as bolus and are equally effective. Combination chemotherapy mixes phase-specific and non-specific drugs to hit cells across all states.
Targeted + biological therapies don't fit the classical cycle map. Trastuzumab, rituximab, imatinib, checkpoint inhibitors target signalling or surface antigens regardless of cycle phase. Hormonal agents act on transcription factors. Their toxicity profiles differ from cytotoxic drugs (less bone marrow suppression, but with class-specific effects: trastuzumab cardiotoxicity, imatinib oedema, checkpoint inhibitors immune-related adverse events).
Figure 1 · Step-by-step anticancer drug attack on a single tumour cell — drugs are added one by one (tap ▶ Play or step buttons)
Step 1 of 7
Figure 2 · Anticancer drug targets — vertical biosynthetic pathway with drugs added on BOTH SIDES at each step (tap ▶ Play or step buttons)
Clinical translation: works best on rapidly dividing cells — explains why haematopoietic + GI + germ + hair tissues bear the brunt of toxicity, and why CCS drugs (S- or M-phase) need either continuous infusion (cytarabine 5–7 d in AML) or repeated low-dose schedules to catch most cells in the vulnerable phase. CCNS drugs (alkylators, anthracyclines) are bolus-effective and hit slow-growing tumours too.
Resistance escapes: p53 mutations make tumour cells refractory to apoptosis (most cancers carry p53 loss); MDR1 efflux pumps export drug; altered drug targets (DHFR amplification → MTX resistance); enhanced DNA repair (HR/NHEJ → platinum resistance).
Mechanism (small-molecule TKI): compete with ATP at the kinase domain ATP-binding pocket → block phosphorylation of downstream substrates → halt growth signalling. Imatinib for BCR-ABL fusion in CML; gefitinib/erlotinib/osimertinib for activating EGFR mutations in NSCLC; vemurafenib for BRAF V600E in melanoma; crizotinib for ALK fusions; sorafenib/sunitinib multi-kinase.
Mechanism (mAb): bind extracellular domain of surface receptor → block ligand binding (trastuzumab/HER2, cetuximab/EGFR) OR mark cell for immune destruction via Fc → ADCC by NK cells + complement-dependent cytotoxicity (rituximab/CD20, alemtuzumab/CD52). Antibody-drug conjugates (T-DM1, brentuximab) deliver cytotoxic payload selectively.
Clinical translation: companion diagnostic FIRST (HER2 IHC/FISH, EGFR mutation testing, BRAF testing, BCR-ABL transcript), THEN drug. Targeted drugs spare bone marrow → less myelosuppression but new class-specific toxicities (trastuzumab cardiotoxicity, EGFR-TKI rash + diarrhoea, multi-kinase hand-foot, BRAF hyperkeratosis).
📖 Hormonal therapy — tamoxifen / aromatase inhibitors for ER+ breast; GnRH agonists + anti-androgens for prostate
Mechanism (breast): tamoxifen — competitive ER antagonist in breast tissue (partial agonist in uterus + bone). Raloxifene — pure SERM. Aromatase inhibitors (anastrozole, letrozole, exemestane) — block peripheral conversion of androgens to oestrogen → suppress ER-driven growth in post-menopausal ER+ breast. Fulvestrant — ER antagonist that also degrades the receptor.
Clinical translation: 5-year tamoxifen reduces recurrence by 50% in ER+ breast; aromatase inhibitor = post-menopausal first-line. ADT (GnRH + anti-androgen) is backbone of metastatic prostate cancer. Toxicities: hot flushes, osteoporosis (DEXA monitoring), increased VTE risk (tamoxifen).
📖 Checkpoint inhibitors — anti-PD-1 / anti-PD-L1 / anti-CTLA-4 reactivate exhausted T cells; irAE class signature
Mechanism: tumour cells co-opt physiological T-cell brakes by expressing PD-L1 (binds PD-1 on T cells → exhaustion). CTLA-4 limits early T-cell activation in lymph nodes. Antibodies block these checkpoints → reactivate exhausted tumour-infiltrating lymphocytes → durable T-cell-mediated anti-tumour immunity. PD-1 mAbs: nivolumab, pembrolizumab. PD-L1: atezolizumab, durvalumab. CTLA-4: ipilimumab. Combination ipi+nivo for melanoma.
Clinical translation: game-changing in melanoma (5-year OS now 50%+ from <10%), NSCLC (PD-L1 high → first-line monotherapy), RCC, urothelial, MSI-high tumours, Hodgkin lymphoma. Companion biomarkers — PD-L1 IHC, MSI, TMB.
Class signature toxicity = immune-related adverse events (irAEs): any organ — colitis (most common), hypophysitis + thyroiditis + adrenal insufficiency, hepatitis, pneumonitis, dermatitis, myocarditis, type-1 diabetes, autoimmune neurologic. Manage with corticosteroids; severe → hold drug + add infliximab. Pharmacist counselling is critical: "any new symptom, however small, contact us."
📖 Differentiating agents — ATRA matures APL blasts; asparaginase starves ALL; bortezomib for MM; PARP for BRCA-mut
ATRA (all-trans retinoic acid): binds RAR → forces malignant promyelocytes in APL to mature into normal granulocytes. Combined with arsenic trioxide → 90%+ cure in low-risk APL. Watch for differentiation syndrome (fever, dyspnoea, fluid retention) — treat with high-dose steroids.
Asparaginase / pegaspargase / crisantaspase: deaminates extracellular asparagine. Normal cells make asparagine via asparagine synthetase; ALL blasts cannot — selective starvation. Toxicity: hypersensitivity, pancreatitis, coagulopathy, hyperglycaemia.
Proteasome inhibitors (bortezomib, carfilzomib, ixazomib): block 26S proteasome → accumulation of misfolded proteins → ER stress → apoptosis (myeloma cells produce huge amounts of immunoglobulin and are exquisitely sensitive).
CDK4/6 inhibitors (palbociclib, ribociclib, abemaciclib): block G1→S progression in HR+/HER2− breast cancer when added to AI. Hydroxyurea — RNR inhibitor → ↓ dNTPs (CML, sickle cell). PARP inhibitors (olaparib, niraparib) → synthetic lethality in BRCA-mutant ovarian + breast cancers.
Targeted addition: Philadelphia (BCR-ABL+) ALL → imatinib or dasatinib added throughout. Cure rate: paediatric ~90%; adult ~40–50% with MRD-driven adjustment.
📖 AML — "7+3" induction (cytarabine 7 d + daunorubicin 3 d); add midostaurin if FLT3-mut; ATRA + ATO if APL
Induction "7+3": cytarabine 100–200 mg/m² CONTINUOUS infusion × 7 days + daunorubicin 60 mg/m² IV days 1–3. Day-14 marrow → second induction if residual blasts. Consolidation: high-dose cytarabine 3 g/m² q12h × 6 doses (3 cycles). Targeted: FLT3-mut → midostaurin / gilteritinib added. IDH1/2-mut → ivosidenib / enasidenib. CD33+ → gemtuzumab ozogamicin. APL (M3 subtype): ATRA + arsenic trioxide → 90% cure (no chemo needed). Allogeneic stem-cell transplant: intermediate/high-risk in CR1 if donor available.
ABVD = doxorubicin (A=adriamycin) + bleomycin + vinblastine + dacarbazine; 28-day cycle, 2–6 cycles + radiation in early stage. Brentuximab vedotin (anti-CD30 ADC) for refractory or AVD-bleomycin-free regimens. Pembrolizumab + nivolumab for relapsed. Cure rate >85%. Watch bleomycin pulmonary fibrosis — avoid high FiO₂, monitor PFTs.
📖 NHL — R-CHOP (rituximab + cyclophosphamide + doxorubicin + vincristine + prednisolone); HBV screen before rituximab
R-CHOP = rituximab + cyclophosphamide + doxorubicin (Hydroxydaunorubicin) + vincristine (Oncovin) + prednisolone; 21-day cycle × 6–8. Standard for diffuse large B-cell lymphoma (DLBCL). Add radiation for bulky disease. Pola-R-CHP (polatuzumab) for high-risk. CAR-T (axicabtagene ciloleucel, lisocabtagene) for refractory. Mesna NOT needed at standard cyclophosphamide dose. Hepatitis B reactivation screen before rituximab.
📖 Breast cancer — AC-T then trastuzumab if HER2+; AI or tamoxifen if ER+; pembrolizumab for high-risk TNBC
AC-T: doxorubicin + cyclophosphamide × 4 cycles → paclitaxel × 12 weeks. HER2+: add trastuzumab + pertuzumab (TCHP regimen — docetaxel + carboplatin + trastuzumab + pertuzumab) for 1 year total. Echo q3 mo. ER+ post-menopausal: aromatase inhibitor (letrozole/anastrozole/exemestane) × 5–10 years. Pre-menopausal → tamoxifen × 5 y or AI + ovarian suppression. Triple-negative: AC-T + carboplatin; consider pembrolizumab for high-risk early-stage.
Mechanism: imatinib competes with ATP at BCR-ABL kinase ATP-pocket → halts constitutive tyrosine kinase activity → restores normal haematopoiesis. Treatment: imatinib 400 mg/d PO; monitor BCR-ABL transcript by RT-PCR every 3 months. Major molecular response (MMR) = BCR-ABL ≤0.1% IS within 12 months. Resistance: T315I mutation → switch to ponatinib. Other resistance → dasatinib, nilotinib, bosutinib. Treatment-free remission: sustained MR4.5 ≥2 y → trial of stopping; ~50% relapse, all respond on re-challenge.
📖 Prostate — GnRH agonist (leuprolide) + anti-androgen (bicalutamide); abiraterone or docetaxel for high-volume
Hormone-sensitive metastatic: leuprolide (GnRH agonist) + bicalutamide (anti-androgen, prevents flare) × 4 weeks → abiraterone + prednisolone OR docetaxel for high-volume. Castration-resistant: abiraterone, enzalutamide, docetaxel, cabazitaxel, radium-223, lutetium-177 PSMA, olaparib if BRCA-mut. PSA monitoring drives response and progression. Side effects: hot flushes, ED, osteoporosis (DEXA + bisphosphonate / denosumab), gynaecomastia.
VRd induction: bortezomib (proteasome inhibitor) SC weekly + lenalidomide (immunomodulator) PO + dexamethasone PO weekly. 4–6 cycles → autologous stem-cell transplant (eligible) → maintenance lenalidomide. Quad regimens: daratumumab (anti-CD38 mAb) added in newly diagnosed (D-VRd). Relapsed: carfilzomib, pomalidomide, isatuximab, elotuzumab, selinexor, CAR-T (idecabtagene, ciltacabtagene), bispecific antibodies (teclistamab, talquetamab). Supportive: bisphosphonates / denosumab for bone lesions; VTE prophylaxis on lenalidomide.
7. Adverse Drug Reactions — Class + Drug-Specific
Click each ADR for mechanism, signs/symptoms, management.
⚠️ Myelosuppression — bone marrow stem cell death; neutropenic nadir 7–14 days; febrile neutropenia risk
Mechanism: bone marrow stem cells are rapidly dividing → killed by CCS and CCNS drugs. Signs: nadir 7–14 days post-chemo — neutropenia (febrile neutropenia risk), thrombocytopenia (bleeding), anaemia. Management: filgrastim G-CSF for neutropenia; platelet transfusion if <10,000; erythropoietin for anaemia (caution in some tumours). Empirical antibiotics for febrile neutropenia. Schedule next cycle when ANC >1500.
Mechanism: rapid GI epithelial turnover → killed by chemo. Signs: mouth ulcers, throat pain, diarrhoea, abdominal cramps. Management: palifermin (KGF) for severe mucositis; ice chips during 5-FU to vasoconstrict oral mucosa; loperamide for diarrhoea; counsel on hygiene and diet.
Mechanism: bleomycin generates free radicals; lung has low bleomycin hydrolase. Signs: dry cough, dyspnoea, restrictive pattern on PFT; 10% incidence; can be fatal. Management: baseline + serial PFTs (DLCO); cumulative dose <400 units; avoid high FiO₂ during anaesthesia (worsens damage); stop drug if early signs.
Mechanism: acrolein metabolite excreted in urine → bladder mucosal damage. Signs: haematuria, dysuria, suprapubic pain. Management: mesna (sodium 2-mercaptoethane sulfonate) IV before + 4 + 8 h after chemo binds acrolein in urine; vigorous hydration; bladder catheter irrigation if severe.
⚠️ Vincristine peripheral neuropathy — microtubule disruption in axonal transport; dose cap 2 mg; NEVER intrathecal
Mechanism: microtubule disruption affects axonal transport in peripheral nerves. Signs: dose-cumulative — paraesthesia, loss of deep tendon reflexes, foot drop, paralytic ileus. Management: dose cap 2 mg per dose; reduce dose or stop if severe neuropathy; symptomatic treatment with gabapentinoids; NEVER intrathecal — fatal.
Mechanism: DHFR inhibition depletes tetrahydrofolate → blocks DNA synthesis in normal tissue. Signs: mucositis, hepatotoxicity, myelosuppression, renal damage at high dose. Management: leucovorin (folinic acid) rescue 24 h after high-dose MTX bypasses DHFR block in normal cells (spares MTX in tumour). Glucarpidase for MTX overdose. Avoid NSAIDs (raise MTX levels).
⚠️ Tumour lysis syndrome (TLS) — rapid cell death releases K⁺ + PO₄³⁻ + uric acid; AKI risk; allopurinol/rasburicase + IV fluids
Mechanism: rapid cell death releases intracellular K⁺, PO₄³⁻, uric acid → metabolic emergency. Signs: hyperkalaemia, hyperphosphataemia, hyperuricaemia, hypocalcaemia, AKI. Management: prophylactic allopurinol or rasburicase + IV hydration for high-risk tumours (Burkitt lymphoma, ALL with high WBC). Monitor electrolytes. Dialysis if severe.
Mechanism: NSAIDs reduce renal blood flow + competitively inhibit MTX tubular secretion (organic anion transporter) → MTX clearance falls → toxic plasma levels (myelosuppression, mucositis, AKI). Severity: high — fatalities reported with high-dose MTX + NSAIDs. Action: avoid NSAIDs around high-dose MTX (hold 24 h before, 48–72 h after). Low-dose oral MTX for RA can usually continue with NSAIDs but counsel for symptoms. Use paracetamol instead. Monitor MTX level + creatinine.
📖 MTX + cotrimoxazole — TMP additive folate antagonism → pancytopenia; avoid; use alternative antibiotic
Mechanism: trimethoprim is a weak DHFR inhibitor → additive folate antagonism with MTX → megaloblastic anaemia + pancytopenia. Sulfamethoxazole displaces MTX from albumin. Severity: very high — avoid combination. Action: use alternative antibiotic (amoxicillin, doxycycline) for routine infection. If cotrimoxazole essential (PCP prophylaxis in high-dose MTX patient) → reduce/hold MTX, supplement with leucovorin, monitor CBC + MTX level closely.
📖 5-FU + warfarin — 5-FU/capecitabine inhibit CYP2C9 → ↑ INR; switch to DOAC during chemo
Mechanism: 5-FU and capecitabine inhibit CYP2C9 → ↓ S-warfarin metabolism → INR rises within 1–2 weeks of starting chemo, persisting weeks after. Severity: high — major haemorrhage reported. Action: if anticoagulation required, switch to a DOAC (apixaban, rivaroxaban) or LMWH for chemo duration. If continuing warfarin, halve dose at chemo start, monitor INR weekly, anticipate dose increases at chemo end.
Mechanism: all small-molecule TKIs are CYP3A4 substrates. INHIBITORS (clarithromycin, itraconazole, ritonavir, grapefruit juice, voriconazole) raise plasma levels → toxicity. INDUCERS (rifampicin, phenytoin, carbamazepine, St John's Wort) lower levels → loss of efficacy. Severity: high — therapeutic failure or toxicity. Action: screen all new prescriptions and OTC against CYP3A4 list. Avoid grapefruit. Use azithromycin instead of clarithromycin. If induction unavoidable, double TKI dose with TDM.
Mechanism: all three classes damage proximal tubular cells (cisplatin via DNA adducts, aminoglycosides via mitochondrial dysfunction) and cochlear outer hair cells. Effects are additive. Severity: very high. Action: avoid concurrent gentamicin/tobramycin/amikacin. Use beta-lactams or fluoroquinolones for infection. Furosemide → spironolactone where possible. Mandatory: pre-cisplatin hydration with NaCl + KCl + MgSO₄ + mannitol, baseline + serial creatinine + audiometry. Switch to carboplatin if eGFR <60.
📖 Anthracyclines + trastuzumab — concurrent use ↑ HF rate 1%→27%; SEQUENCE doxorubicin THEN trastuzumab
Mechanism: doxorubicin generates iron-mediated free radicals → cardiomyocyte damage. Trastuzumab blocks HER2 signalling needed for cardiac stress repair → unmasks damage. Concurrent use ↑ heart-failure rate from 1% → 27%. Severity: very high. Action: SEQUENCE — finish anthracycline FIRST → wait 3 months → start trastuzumab. Echo / MUGA at baseline + every 3 months on trastuzumab. Hold trastuzumab if LVEF drops >10% absolute or below 50%. Use liposomal doxorubicin (Doxil) or replace with non-anthracycline (TCH = docetaxel + carboplatin + trastuzumab).
📖 Allopurinol + 6-MP / azathioprine — XO block → 4× drug accumulation → fatal pancytopenia; reduce to 25%
Mechanism: 6-MP and azathioprine (prodrug → 6-MP) are inactivated by xanthine oxidase. Allopurinol blocks XO → 6-MP accumulates 4-fold → severe myelosuppression. Severity: very high — fatal pancytopenia reported. Action: if both required, REDUCE 6-MP/azathioprine by 75% (i.e., to ¼ dose) and monitor CBC weekly for 4 weeks then monthly. Consider febuxostat (also XO inhibitor — same problem) vs alternative urate management. Genotype TPMT — homozygous deficient + allopurinol → catastrophic.
📖 Live vaccines during chemo — ↓ cell-mediated immunity → disseminated vaccine virus; AVOID 6 mo post-chemo
Mechanism: chemotherapy suppresses cell-mediated immunity → live attenuated vaccine (MMR, BCG, varicella, yellow fever, intranasal influenza, oral typhoid, oral polio, rotavirus) can cause systemic disease. Severity: very high — fatal in profoundly immunosuppressed. Action: NO live vaccines during chemo and for 6 months after. Ideally complete vaccinations 4 weeks BEFORE starting chemo. Inactivated vaccines (flu shot, COVID, pneumococcal) are safe and recommended (but reduced response). Family contacts CAN have most live vaccines except oral polio (now historic).
9. Contraindications
Outline
Absolute: pregnancy (most cytotoxics teratogenic) · breastfeeding · severe myelosuppression · active severe infection · live vaccines Drug-specific: doxorubicin in pre-existing cardiomyopathy · bleomycin in pulmonary fibrosis · cisplatin in renal failure · vincristine in severe neuropathy · methotrexate in severe renal/hepatic impairment Caution: elderly, performance status <2, multiple comorbidities
📌 Outline above lists the absolute and relative contraindications. Tap each card for full reasoning + workaround.
📖 Pregnancy — embryotoxic + teratogenic; absolute in 1st trimester; counsel contraception 6 mo post
Mechanism: alkylators + antimetabolites + topoisomerase poisons cross placenta and damage rapidly dividing fetal tissues — risk of malformation, growth restriction, fetal demise, secondary leukaemia, infertility. Severity: absolute in 1st trimester (organogenesis). 2nd/3rd trimester some agents possible (anthracyclines + cyclophosphamide for breast cancer in pregnancy with informed consent). MTX, hormonal agents, retinoids = ABSOLUTELY contraindicated entire pregnancy. Counselling: highly effective contraception during chemo + 6 months after for women, 3 months for men. Discuss fertility preservation BEFORE chemo (oocyte / sperm cryopreservation). Pregnancy testing pre-cycle. Termination discussion if pregnancy in trimester 1.
📖 Severe bone-marrow suppression — wait for ANC ≥1500 + plt ≥100,000 + Hb >9 before next cycle
Mechanism: previous cycle has not recovered → next cycle would cause life-threatening cytopenias (febrile neutropenia, bleeding, transfusion-dependent anaemia). Threshold: ANC ≥1500 + platelets ≥100,000 + Hb >9 before next cycle. Action: dose-reduce 25–50% if persistent toxicity. Add G-CSF prophylaxis (filgrastim / pegfilgrastim) for high-risk regimens. Delay cycle 1 week if not recovered.
📖 Active severe infection — chemo deepens neutropenia → uncontrollable; treat HBV + TB before mAbs
Mechanism: chemo deepens neutropenia → infection becomes uncontrollable. Action: treat infection to clinical stability + obtain neg cultures FIRST. If chemo cannot be delayed (aggressive lymphoma), protect with broad-spectrum antibiotics + G-CSF + close monitoring. Treat HBV + TB latent infection BEFORE rituximab + checkpoint inhibitors.
📖 Severe hepatic impairment — reduce doxorubicin/vincristine/paclitaxel/irinotecan; UGT1A1 genotype for irinotecan
Affected drugs: doxorubicin (50–75% dose reduction if bilirubin >1.5), vincristine (avoid if bilirubin >3), paclitaxel (significant reduction), irinotecan (UGT1A1*28 + raised bilirubin → severe neutropenia). Action: baseline LFTs + UGT1A1 genotype before irinotecan. Switch to renally-cleared alternative (carboplatin instead of cisplatin if also liver issues). Reverse-distribution check.
📖 Severe renal impairment — high-dose MTX absolute CI <60 eGFR; cisplatin → carboplatin AUC-Calvert; lenalidomide adjust
Common offenders: paclitaxel (Cremophor vehicle — not the drug), platinum (cisplatin, carboplatin, oxaliplatin — IgE-mediated; risk rises after 6 cycles), L-asparaginase (E. coli protein), rituximab (cytokine-release), monoclonal antibodies in general. Action: standard paclitaxel premedication = dexamethasone 20 mg PO 12 + 6 h before + diphenhydramine + ranitidine. Nab-paclitaxel (albumin-bound, no Cremophor) avoids the issue. Platinum desensitisation protocols available. Alternative class: oxaliplatin → carboplatin if oxaliplatin allergy. Anaphylaxis kit at every infusion chair.
10. Clinical Context / Pathology
📚 Clinical context
Chemotherapy is given in cycles every 2–4 weeks for normal tissue recovery. Combination regimens with non-overlapping toxicities reduce resistance (CHOP, R-CHOP, BEACOPP, FOLFOX, BEP). Three eras: cytotoxic (1940s+) → targeted (2000+) → immunotherapy (2015+). Pharmacist role: dispense + counsel + manage side effects + monitor TKI interactions + contraception counselling + supportive care (ondansetron, filgrastim, mesna, leucovorin) + palliative care support.
Unifying theme: every regimen balances tumour control against organ-specific toxicity.