Anticancer drugs and immunopharmacology

In short

Anticancer (antineoplastic) pharmacology deals with drugs that kill or arrest rapidly dividing malignant cells, while immunopharmacology deals with drugs that suppress, stimulate or redirect the immune system — immunosuppressants for transplants and autoimmune disease, immunostimulants and vaccines, and the newer biologicals that make tumours visible to immune cells. The two subjects now overlap almost completely, because checkpoint inhibitors, monoclonal antibodies and CAR-T cells are anticancer drugs that work through immunity. This unit is examined in B.Pharm Pharmacology-III (PCI syllabus, semester VI), in GPAT and NIPER entrance papers, and in interviews for oncology medical affairs, pharmacovigilance, clinical research and oncology product manufacturing (Cipla, Dr Reddy's, Natco, Intas/Biocon, Emcure, Zydus, Hetero). Dose calculation by body surface area, cell-cycle specificity, resistance mechanisms and organ-specific toxicities are the reliably repeated questions.

Explained

Basic principles of cancer chemotherapy

• Cancer - uncontrolled clonal proliferation with loss of contact inhibition, invasion and metastasis; driven by activated oncogenes (RAS, MYC, BCR-ABL) and lost tumour suppressors (p53, RB).
• Cell-cycle kinetics: G0 (resting) → G1 (synthesis of enzymes) → S (DNA replication) → G2 (protein synthesis) → M (mitosis). Drugs acting only in one phase are cell-cycle specific (CCS); those acting in all phases including G0 are cell-cycle non-specific (CCNS).
• Log-kill hypothesis (Skipper): a given dose kills a constant *fraction*, not a constant number, of cells. A 3-log kill reduces 10¹² cells to 10⁹ — never to zero, so repeated cycles plus host immunity are needed.
• Gompertzian growth: small tumours grow fast (high growth fraction, chemo-sensitive); large bulky tumours have a low growth fraction and many G0 cells, so surgery/radiation first (debulking) makes chemotherapy work better.
• Why combinations: use drugs with proven single-agent activity, different mechanisms, non-overlapping toxicities and no cross-resistance, each at full dose — e.g. CHOP, ABVD, FOLFOX, BEP, CMF.
• Therapy intent: *neoadjuvant* (before surgery, to shrink), *adjuvant* (after surgery, to kill micrometastases), *curative* (testicular cancer, choriocarcinoma, ALL, Hodgkin lymphoma), *palliative*.
• Pulse/cyclic dosing every 21-28 days allows normal marrow (and gut mucosa) to recover; the nadir of blood counts is usually day 7-14.
• Resistance: decreased uptake or increased efflux by P-glycoprotein (MDR1), increased drug-inactivating enzymes, increased target enzyme or altered target, better DNA repair, loss of apoptotic machinery (p53 mutation).

Classification of anticancer drugs

1. Alkylating agents (CCNS) — transfer alkyl groups to DNA N7-guanine, causing cross-links and strand breaks.
   • Nitrogen mustards: cyclophosphamide (prodrug, activated by hepatic CYP to phosphoramide mustard + acrolein → haemorrhagic cystitis, prevented by mesna and hydration), ifosfamide, chlorambucil, melphalan, bendamustine.
   • Nitrosoureas: carmustine, lomustine — lipid-soluble, cross the blood-brain barrier (brain tumours).
   • Others: busulfan (pulmonary fibrosis), dacarbazine, temozolomide, thiotepa.
   • Platinum compounds (alkylating-like): cisplatin — nephrotoxic, severely emetogenic, ototoxic, peripheral neuropathy; carboplatin — myelosuppressive instead; oxaliplatin — cold-induced neuropathy (FOLFOX in colorectal cancer).
2. Antimetabolites (CCS, S-phase) — structural analogues that block nucleotide synthesis.
   • Folate antagonist: methotrexate inhibits dihydrofolate reductase → no THF → no thymidylate/purines. Rescue with leucovorin (folinic acid); toxicity worsened by NSAIDs, sulfonamides and renal impairment.
   • Pyrimidine antagonists: 5-fluorouracil → FdUMP inhibits thymidylate synthase (hand-foot syndrome, mucositis; DPD deficiency causes severe toxicity); capecitabine (oral prodrug of 5-FU); cytarabine (AML); gemcitabine (pancreatic, lung).
   • Purine antagonists: 6-mercaptopurine (needs TPMT; allopurinol raises its levels — reduce dose to about one-fourth), 6-thioguanine, fludarabine, hydroxyurea (inhibits ribonucleotide reductase; also used in sickle cell disease).
3. Vinca alkaloids and taxanes (CCS, M-phase)
   • Vincristine, vinblastine, vinorelbine — bind tubulin, prevent polymerisation; vincristine is dose-limited by peripheral neuropathy (not marrow) and is fatal if given intrathecally — strictly intravenous.
   • Paclitaxel, docetaxel — stabilise microtubules, prevent depolymerisation; hypersensitivity to the cremophor vehicle needs premedication with dexamethasone and antihistamines; neuropathy, alopecia.
   • Etoposide (podophyllotoxin) and topotecan/irinotecan (camptothecins) inhibit topoisomerase II and I respectively; irinotecan causes early cholinergic and late severe diarrhoea.
4. Cytotoxic antibiotics (mostly CCNS)
   • Doxorubicin, daunorubicin, epirubicin, idarubicin — intercalate DNA, inhibit topoisomerase II, generate free radicals → dose-related, cumulative cardiomyopathy; limit lifetime dose, use dexrazoxane or liposomal formulations; red urine is harmless.
   • Bleomycin — free-radical DNA breaks; pulmonary fibrosis is dose-limiting, minimal myelosuppression.
   • Actinomycin D (dactinomycin) — Wilms' tumour; mitomycin C — bioreductive alkylator.
5. Hormonal and anti-hormonal agents
   • Breast: tamoxifen (SERM — antagonist in breast, agonist in endometrium → endometrial carcinoma and VTE risk; needs CYP2D6 to form endoxifen), aromatase inhibitors letrozole/anastrozole/exemestane (postmenopausal only; osteoporosis), fulvestrant (ER degrader).
   • Prostate: GnRH agonists leuprorelin (leuprolide)/goserelin (initial testosterone flare — cover with an antiandrogen), GnRH antagonist degarelix, antiandrogens bicalutamide, enzalutamide, abiraterone (CYP17 inhibitor).
   • Prednisolone (lympholytic in ALL, lymphoma, myeloma; also antiemetic and appetite-stimulant).
6. Targeted small molecules
   • Imatinib — BCR-ABL tyrosine kinase inhibitor, the landmark drug of CML (also c-KIT in GIST); later generations dasatinib, nilotinib, ponatinib.
   • Gefitinib, erlotinib, osimertinib (EGFR-mutant NSCLC — acneiform rash correlates with response); lapatinib; crizotinib (ALK); sorafenib, sunitinib, pazopanib (multikinase/antiangiogenic); ibrutinib (BTK); palbociclib (CDK4/6); olaparib (PARP inhibitor, BRCA-mutated); bortezomib, carfilzomib (proteasome inhibitors in myeloma); all-trans retinoic acid (ATRA) forces differentiation in APL — watch for differentiation syndrome.
7. Biologicals and immuno-oncology
   • Monoclonals: rituximab (CD20), trastuzumab and pertuzumab (HER2 — cardiotoxic, usually reversible, mandatory echocardiographic LVEF monitoring), bevacizumab (VEGF — hypertension, bleeding, impaired wound healing), cetuximab (EGFR; useless in KRAS-mutant tumours), antibody-drug conjugates (trastuzumab emtansine, brentuximab vedotin).
   • Immune checkpoint inhibitors: nivolumab, pembrolizumab (anti-PD-1), atezolizumab (PD-L1), ipilimumab (CTLA-4) — release the brakes on cytotoxic T cells; cause immune-related adverse events (colitis, hepatitis, thyroiditis, hypophysitis, pneumonitis) treated with corticosteroids, not more chemo.
   • CAR-T cells — autologous T cells engineered with a chimeric antigen receptor against CD19 (B-ALL, DLBCL); principal toxicities are cytokine release syndrome (treated with tocilizumab, an IL-6 receptor blocker) and neurotoxicity. India approved its first indigenous CD19 CAR-T, NexCAR19 (actalycabtagene autoleucel), in 2023 — cost is a fraction of imported products but still in lakhs of rupees.
   • Asparaginase (enzyme; depletes asparagine in ALL — hypersensitivity, pancreatitis), interferon-α, IL-2 (aldesleukin), BCG instilled intravesically for superficial bladder cancer.

Toxicity and supportive care

• Common to most cytotoxics: bone-marrow suppression (neutropenia, thrombocytopenia, anaemia), mucositis and diarrhoea, alopecia, nausea/vomiting, infertility, teratogenicity, secondary malignancies (alkylating agents → AML), hyperuricaemia.
• Febrile neutropenia (ANC <500/µL with fever) is an emergency — blood cultures and empirical broad-spectrum antibiotics within an hour; filgrastim/pegfilgrastim (G-CSF) shortens neutropenia; erythropoietin for anaemia.
• Emesis control: 5-HT3 antagonists (ondansetron, palonosetron) + dexamethasone + NK1 antagonist (aprepitant) for highly emetogenic regimens such as cisplatin; olanzapine is a cheap, effective add-on.
• Tumour lysis syndrome: hyperuricaemia, hyperkalaemia, hyperphosphataemia, hypocalcaemia, acute kidney injury in bulky leukaemia/lymphoma — hydration + allopurinol (prophylaxis) or rasburicase (established, high risk).
• Organ-specific memory list: cyclophosphamide→bladder; doxorubicin→heart; bleomycin/busulfan→lung; cisplatin→kidney, ear, nerve; vincristine→nerve; methotrexate→liver, kidney, lung, mucosa; 5-FU→hand-foot; trastuzumab→heart; checkpoint inhibitors→autoimmune organ damage.
• Handling safety: cytotoxics are prepared in a Class II biological safety cabinet with personal protective equipment and closed-system transfer devices; spill kits and segregated cytotoxic waste (yellow category) per the Bio-Medical Waste Management Rules, 2016 (as amended).

Immunosuppressants and immunostimulants

• Why: prevent and treat organ-transplant rejection and graft-versus-host disease; control autoimmune disease (rheumatoid arthritis, lupus nephritis, inflammatory bowel disease, psoriasis, multiple sclerosis).
• Calcineurin inhibitors: cyclosporine (binds cyclophilin) and tacrolimus (binds FKBP-12) → block calcineurin → no IL-2 transcription → no T-cell proliferation. Both are nephrotoxic, CYP3A4 substrates (ketoconazole, erythromycin and grapefruit raise levels; rifampicin and phenytoin lower them) and need therapeutic drug monitoring. Cyclosporine causes hirsutism and gum hypertrophy; tacrolimus causes more diabetes and neurotoxicity but less cosmetic effect.
• mTOR inhibitors: sirolimus, everolimus — bind FKBP-12 then inhibit mTOR; hyperlipidaemia, poor wound healing, mouth ulcers; not nephrotoxic (useful to spare calcineurin inhibitors).
• Antiproliferatives: azathioprine (→6-MP; dangerous with allopurinol; TPMT genotype matters), mycophenolate mofetil (inhibits inosine monophosphate dehydrogenase, selective for lymphocytes; GI upset; contraindicated in pregnancy), methotrexate (low weekly dose, anchor drug of rheumatoid arthritis), leflunomide, cyclophosphamide (lupus nephritis, vasculitis).
• Glucocorticoids: broad — inhibit NF-κB, reduce cytokines, cause lymphocyte apoptosis and redistribution; the backbone of induction and rejection treatment.
• Antibodies: basiliximab (anti-CD25 induction), antithymocyte globulin, rituximab (desensitisation, autoimmunity), biologic DMARDs — infliximab, etanercept, adalimumab (TNF-α; screen for latent tuberculosis before starting — essential in India), tocilizumab (IL-6R), ustekinumab/secukinumab (IL-12/23, IL-17), abatacept (CTLA4-Ig co-stimulation blocker), omalizumab (IgE in asthma); tofacitinib/baricitinib are oral JAK inhibitors.
• Shared risks of immunosuppression: infection (including reactivation of tuberculosis, hepatitis B, CMV, herpes zoster), lymphoma and skin cancer, poor vaccine response — live vaccines are contraindicated.
• Immunostimulants: BCG, levamisole, interferons, thalidomide/lenalidomide (immunomodulatory in myeloma — strictly teratogenic, pregnancy-prevention programme), G-CSF, and vaccines — active immunisation under India's Universal Immunisation Programme; HPV vaccine (cervical cancer prevention; an indigenous quadrivalent vaccine, Cervavac, was launched in 2023) and hepatitis B vaccine (prevents hepatocellular carcinoma) are the two cancer-preventing vaccines usually asked.
• Immunosuppression vs immunostimulation: opposite goals but the same mediators — a cytokine blocked in arthritis (TNF-α, IL-6) is the same one whose storm is treated after CAR-T.

Screening methods, regulation and Indian practice

• Screening of anticancer agents: in-vitro cytotoxicity on cell lines (MTT, SRB, NCI-60 panel, trypan blue dye exclusion, clonogenic assay); in-vivo transplantable tumours in mice (Ehrlich ascites carcinoma, Dalton's lymphoma, sarcoma-180, P388/L1210 leukaemia), xenografts in nude mice; endpoints are tumour volume, % growth inhibition and increase in lifespan.
• Immunopharmacology screens: carbon-clearance and sheep-RBC haemagglutination titre for phagocytosis/humoral response, delayed-type hypersensitivity footpad test, mitogen-induced lymphocyte proliferation, graft rejection models.
• India: cytotoxics, immunosuppressants and biologicals are Schedule H/H1 prescription drugs under the Drugs and Cosmetics Act, 1940 and Rules, 1945; clinical trials and new-drug approval follow the New Drugs and Clinical Trials Rules, 2019 (CDSCO, Subject Expert Committees, registered ethics committees, CTRI registration, compensation for trial injury).
• Similar biologics (biosimilars) follow the CDSCO/DBT Guidelines on Similar Biologics (2016 revision) — India is a major biosimilar producer (trastuzumab, rituximab, bevacizumab, filgrastim).
• Access and cost: many oncology drugs are in the National List of Essential Medicines with ceiling prices fixed by NPPA under the Drug (Prices Control) Order, 2013; Ayushman Bharat PM-JAY funds chemotherapy packages; India's first compulsory licence (2012) was for the anticancer drug sorafenib. Exact prices and NLEM entries are revised periodically — verify current NPPA notifications before quoting.
• Some cytotoxics are also narcotic-free but hazardous; disposal, transport and pharmacovigilance reporting (PvPI, Form for suspected ADR) apply.

Key points

• Cell-cycle specific (CCS) - kills cells only in one phase (antimetabolites in S, vinca/taxanes in M); best given by prolonged infusion.
• Cell-cycle non-specific (CCNS) - kills resting and dividing cells (alkylating agents, platinum, anthracyclines); dose-dependent, best as bolus.
• Log-kill - each cycle kills a fixed fraction of cells, so cure needs repeated cycles plus immune clearance.
• Growth fraction - proportion of cells actively cycling; high in leukaemias (chemo-curable), low in bulky solid tumours.
• Mesna - thiol that binds acrolein and prevents cyclophosphamide/ifosfamide haemorrhagic cystitis.
• Leucovorin rescue - folinic acid bypasses DHFR block and saves normal cells after high-dose methotrexate.
• Vincristine - never intrathecal (fatal); dose-limiting toxicity is neuropathy, not myelosuppression.
• Doxorubicin - cumulative, dose-related cardiomyopathy; limit lifetime dose, use dexrazoxane or liposomal form.
• Bleomycin - pulmonary fibrosis, little marrow toxicity; monitor lung function.
• Cisplatin - most emetogenic; needs saline hydration and triple antiemetics; nephro-, oto- and neurotoxic.
• Imatinib - proof of concept for targeted therapy; inhibits BCR-ABL in chronic myeloid leukaemia.
• Trastuzumab - HER2 monoclonal; test HER2 status first; monitor LVEF for reversible cardiotoxicity.
• Checkpoint inhibitors - anti-PD-1/PD-L1/CTLA-4; adverse effects are autoimmune and need steroids.
• Calcineurin inhibitors - cyclosporine and tacrolimus block IL-2 transcription; nephrotoxic, CYP3A4-dependent, need blood-level monitoring.
• Mycophenolate - inhibits IMPDH; lymphocyte-selective because lymphocytes lack the salvage pathway.
• Azathioprine + allopurinol - dangerous combination; xanthine oxidase block causes severe myelosuppression.
• TNF-α blockers - screen for latent tuberculosis before use; live vaccines contraindicated in all immunosuppressed patients.
• Tumour lysis syndrome - high K⁺, PO₄³⁻, uric acid with low Ca²⁺; prevent with hydration and allopurinol/rasburicase.

Formulas and examples

Example 1 — BSA and cyclophosphamide dose. Woman, 160 cm, 60 kg; CMF regimen, cyclophosphamide 600 mg/m².

• BSA = √(160 × 60 / 3600) = √(9600/3600) = √2.6667 = 1.63 m²
• Dose = 600 × 1.63 = 978 mg → practically rounded to 1,000 mg (vials of 500 mg).
• 5-FU at 600 mg/m² = 978 mg; methotrexate at 40 mg/m² = 65.2 mg ≈ 65 mg.

Example 2 — Calvert formula for carboplatin. Man, 60 years, 70 kg, serum creatinine 1.0 mg/dL, target AUC 5.

• CrCl = [(140 − 60) × 70] / (72 × 1.0) = 5600/72 = 77.8 mL/min
• Dose = 5 × (77.8 + 25) = 5 × 102.8 = 514 mg ≈ 510 mg rounded to vial size.
• If serum creatinine were 2.0 mg/dL, CrCl = 38.9 → dose = 5 × 63.9 = 319 mg — i.e. renal impairment nearly halves the dose.

Example 3 — Log kill and cycles needed. A lymphoma has 10¹² cells; each cycle gives a 2-log kill (99% killed, f = 0.99), and between cycles the tumour regrows 1 log.

• Net kill per cycle = 2 − 1 = 1 log.
• Cells after 1 cycle = 10¹¹; after 6 cycles = 10¹² × 10⁻⁶ = 10⁶ cells.
• To reach 10⁰ (one cell) needs 12 cycles — which is why maintenance therapy and immune clearance matter, and why dose-dense schedules that cut regrowth time improve cure rates.

Example 4 — Absolute neutrophil count and a dose decision. Day-10 counts after FOLFOX: total WBC 1,800/µL, neutrophils 22%, bands 3%.

• ANC = 1,800 × (22 + 3)/100 = 1,800 × 0.25 = 450/µL → Grade 4 neutropenia.
• With fever ≥38.3 °C this is febrile neutropenia: cultures and empirical antibiotics within 1 hour, G-CSF support, and the next cycle delayed with a dose reduction (commonly 20-25%) per protocol.

Example 5 — Doxorubicin cumulative dose. Patient of BSA 1.70 m² on doxorubicin 60 mg/m² every 3 weeks.

• Dose per cycle = 60 × 1.70 = 102 mg.
• After 4 cycles, cumulative = 408 mg → 408/1.70 = 240 mg/m².
• Conventional cumulative ceiling is about 450-550 mg/m² (lower with prior chest irradiation or trastuzumab), so roughly 7-9 such cycles is the practical limit; echocardiography is used to decide beyond this.

Where it is used

• Oncology formulation and manufacturing: dedicated cytotoxic blocks with containment and negative-pressure areas at Cipla, Dr Reddy's, Natco, Intas, Zydus, Emcure, Hetero — roles in production, QA/QC, validation and cleaning-validation of cytotoxic lines.
• Biosimilars and biologics: Biocon, Dr Reddy's and Intas make trastuzumab, rituximab, bevacizumab, filgrastim and pegfilgrastim for India and export — pharmacologists work on comparability, immunogenicity and regulatory dossiers.
• Hospital and clinical pharmacy: central drug-admixture units at Tata Memorial, AIIMS, CMC Vellore, regional cancer centres — BSA-based dose verification, extravasation and antiemetic protocols, chemotherapy counselling.
• Clinical research and pharmacovigilance: oncology CRO/CRA roles under the New Drugs and Clinical Trials Rules, 2019; signal detection for immune-related adverse events; adverse-event reporting to PvPI (NCC-IPC, Ghaziabad).
• Transplant and rheumatology practice: therapeutic drug monitoring of cyclosporine/tacrolimus, biologic DMARD dispensing with tuberculosis screening, biosimilar switching support.
• Medical affairs and medico-marketing: oncology and immunology product managers, MSLs explaining HER2/EGFR/PD-L1 biomarker testing to oncologists.

Interview questions

• Q: What is the log-kill hypothesis and what does it imply for treatment? A: Each chemotherapy dose kills a constant fraction of tumour cells, not a fixed number; so repeated cycles are needed and no single dose can eradicate a tumour, with the host immune system clearing the last cells.
• Q: Why are drugs combined rather than given alone? A: To attack different targets, prevent emergence of resistant clones and keep each drug at full dose by choosing agents with non-overlapping toxicities.
• Q: Which anticancer drug needs mesna and why? A: Cyclophosphamide (especially ifosfamide) — its metabolite acrolein injures the bladder urothelium, and mesna binds acrolein in urine to prevent haemorrhagic cystitis.
• Q: Explain leucovorin rescue. A: After high-dose methotrexate, folinic acid supplies reduced folate directly, bypassing the blocked dihydrofolate reductase, and rescues normal marrow and mucosa while tumour cells that take up less folate stay damaged.
• Q: Why must vincristine never be given intrathecally? A: Intrathecal vincristine causes fatal ascending myeloencephalopathy; it is a strictly intravenous drug, and labels and syringes are kept separate from intrathecal methotrexate or cytarabine.
• Q: Doxorubicin and trastuzumab both affect the heart — how do they differ? A: Doxorubicin causes cumulative, dose-related and largely irreversible cardiomyopathy through free radicals; trastuzumab causes non-cumulative, usually reversible LVEF decline, and the two together greatly increase risk.
• Q: How does imatinib work and why was it a breakthrough? A: It occupies the ATP-binding site of the BCR-ABL fusion tyrosine kinase in chronic myeloid leukaemia, blocking the single driver lesion — the first clear proof that a molecularly targeted oral drug can control a cancer.
• Q: What are immune checkpoint inhibitors and how are their side effects managed? A: Antibodies against PD-1, PD-L1 or CTLA-4 that remove inhibitory signals on T cells; the resulting immune-related adverse events (colitis, hepatitis, thyroiditis, pneumonitis) are managed by withholding the drug and giving corticosteroids.
• Q: Compare cyclosporine and tacrolimus. A: Both inhibit calcineurin and block IL-2 transcription — cyclosporine via cyclophilin, tacrolimus via FKBP-12; tacrolimus is more potent with more diabetes and neurotoxicity, cyclosporine causes hirsutism and gum hypertrophy, and both are nephrotoxic CYP3A4 substrates needing level monitoring.
• Q: Why is azathioprine with allopurinol dangerous? A: Allopurinol inhibits xanthine oxidase, which normally inactivates 6-mercaptopurine, so active metabolite levels rise sharply and cause profound myelosuppression — the dose must be cut to about a quarter or the combination avoided.
• Q: Which vaccines prevent cancer, and which vaccines must be avoided in immunosuppressed patients? A: Hepatitis B vaccine (hepatocellular carcinoma) and HPV vaccine (cervical cancer) prevent cancer; all live vaccines — BCG, oral polio, MMR, varicella, yellow fever — are contraindicated in immunosuppression.
• Q: How is a cytotoxic dose calculated and verified in practice? A: From body surface area by the Mosteller formula (or Calvert's formula using GFR for carboplatin), checked against protocol limits, renal and hepatic function, prior cumulative dose and current blood counts before each cycle.
• Q: Which screening models are used for anticancer activity? A: In-vitro cytotoxicity assays such as MTT and SRB on cell lines, then transplantable tumours in mice (Ehrlich ascites carcinoma, Dalton's lymphoma, P388 leukaemia) and human xenografts in nude mice, measuring growth inhibition and increase in lifespan.

Common mistakes

• Using weight instead of body surface area for cytotoxic doses, or forgetting that carboplatin is dosed by AUC and GFR, not mg/m².
• Mixing up cell-cycle specific and non-specific drugs — and therefore the schedule (infusion versus bolus) they need.
• Attributing the dose-limiting toxicity of vincristine to the marrow; it is neuropathy, just as bleomycin's is lung, not marrow.
• Confusing leucovorin (rescue after methotrexate) with mesna (protects bladder from cyclophosphamide) and dexrazoxane (protects heart from anthracyclines).
• Saying checkpoint inhibitor side effects are treated with more immunosuppressive chemotherapy; they are treated with corticosteroids and drug interruption.
• Giving tamoxifen to premenopausal patients' postmenopausal regimen or vice versa — aromatase inhibitors work only after menopause, when ovarian oestrogen synthesis has stopped.
• Forgetting pre-treatment checks: HER2/EGFR/PD-L1 biomarker status, latent tuberculosis before TNF blockers, TPMT before thiopurines, and pregnancy prevention with thalidomide/lenalidomide.
• Treating hyperuricaemia after bulky-tumour chemotherapy as incidental instead of recognising tumour lysis syndrome needing hydration and urate-lowering therapy.

Related topics

• Pharmacodynamics: how drugs act · Antimicrobial drugs · Pharmaceutical biotechnology and biosimilars · Pathophysiology of cancer and cell signalling · Clinical pharmacy and therapeutic drug monitoring · Pharmaceutical jurisprudence: Drugs and Cosmetics Act and NDCT Rules 2019