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analyse_media
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analyse_media
I've used all 5 analyse_media calls. I already have visual input for all 10 images, so I'll now use what I can see directly from the images plus what was extracted to compile the full ordered notes.
Based on all 10 images (5 analysed via tool, 5 read directly as visual input), here is the complete extracted and ordered content:
Chemotherapy Test - Complete Notes (In Order)
Q1. Classification of Anticancer Drugs, Class-Specific Toxicities and Management
I. Classification of Anticancer Drugs
Anticancer drugs are broadly categorised based on their mechanism of action and cellular targets.
A. Cytotoxic (Conventional Chemotherapy)
1. Alkylating agents:
- Nitrogen mustards: Cyclophosphamide, Ifosfamide, Melphalan
- Nitrosoureas: Carmustine, Lomustine
- Alkyl sulfonates: Busulfan
- Triazenes & Hydrazines: Dacarbazine, Temozolomide
2. Platinum Coordination complexes: Cisplatin, Carboplatin, Oxaliplatin
3. Antimetabolites:
- Folate antagonists: Methotrexate, Pemetrexed
- Pyrimidine analogs: 5-Fluorouracil, Capecitabine, Cytarabine, Gemcitabine
- Purine analogs: 6-Mercaptopurine (6-MP), 6-Thioguanine, Fludarabine
4. Natural products / Cytotoxic antibiotics:
- Anthracyclines: Doxorubicin, Daunorubicin, Epirubicin
- Other antibiotics: Bleomycin, Mitomycin-C, Dactinomycin
5. Mitotic spindle inhibitors:
- Vinca alkaloids (inhibit polymerization): Vincristine, Vinblastine, Vinorelbine
- Taxanes (inhibit depolymerization): Paclitaxel, Docetaxel, Cabazitaxel
6. Topoisomerase inhibitors:
- Topoisomerase I inhibitors: Irinotecan, Topotecan
- Topoisomerase II inhibitors: Etoposide, Teniposide
B. Targeted Therapies
1. Small molecule Tyrosine Kinase Inhibitors (TKIs):
- EGFR inhibitors: Erlotinib, Gefitinib, Osimertinib
- BCR-ABL inhibitors: Imatinib, Dasatinib, Nilotinib
- Multi-kinase/VEGFR inhibitors: Sorafenib, Sunitinib, Pazopanib
- ALK inhibitors: Crizotinib, Alectinib
2. Monoclonal antibodies (mAbs):
- Anti-EGFR: Cetuximab, Panitumumab
- Anti-HER2: Trastuzumab, Pertuzumab
- Anti-VEGF: Bevacizumab
- Anti-CD20: Rituximab
3. Antibody-Drug Conjugates (ADCs):
- Trastuzumab deruxtecan (T-DXd)
- Trastuzumab emtansine (T-DM1)
- Sacituzumab govitecan
C. Hormonal Therapies
- Selective Estrogen Receptor Modulators (SERMs): Tamoxifen, Toremifene
- Selective Estrogen Receptor Downregulators (SERDs): Fulvestrant, Elacestrant
- Aromatase inhibitors: Anastrozole, Letrozole (non-steroidal); Exemestane (steroidal)
- GnRH analogues/Antagonists: Leuprolide, Goserelin (agonists); Degarelix, Relugolix (antagonists)
- Antiandrogens: Flutamide, Bicalutamide (First-gen); Enzalutamide, Apalutamide (Second-gen)
D. Immunotherapy & Biological Response Modifiers
1. Immune checkpoint inhibitors:
- Pembrolizumab, Nivolumab, Ipilimumab
2. Cytokines: IL-2, IFN-α
II. Class-Specific Toxicities & Their Management
Drug Class --> Specific Toxicity --> Underlying Mechanism --> Management Strategy
1. Anthracyclines (Doxorubicin):
- Cardiotoxicity
- Acute: Arrhythmias
- Chronic: Dilated cardiomyopathy
- Mechanism: Free radical generation; Topoisomerase II-B inhibition in cardiomyocytes
- Management:
- Cap lifetime cumulative dose (<450-500 mg/m²)
- Co-administer dexrazoxane
- Monitor LVEF
2. Platinum agents (Cisplatin):
- Nephrotoxicity & severe emesis
- Accumulation in central/peripheral nerves; 5-HT3 activation
- Management:
- Aggressive IV hydration with normal saline + mannitol diuresis
- Protocol: Aprepitant + Ondansetron + Dexamethasone + Olanzapine
- Co-administer MESNA to bind & detoxify acrolein
3. Alkylating agents (Cyclophosphamide):
- Haemorrhagic cystitis; Accumulation of its toxic metabolite acrolein in the urinary bladder
- Management:
- Vigorous IV hydration
- Co-administer MESNA to bind & detoxify acrolein
4. Vinca alkaloids (Vincristine):
- Peripheral neuropathy; Disruption of axonal transport; Disruption of mitochondrial transport
- Management:
- Pre-medication protocol: Dexamethasone + Diphenhydramine + Vitamin B6 (Pyridoxine); Famotidine
- Symptomatic: Gabapentin, Pregabalin, Duloxetine
5. Taxanes (Paclitaxel):
- Hypersensitivity reactions (via Cremophor EL vehicle: mediated Histamine release & Vitamin release)
- Hand-foot syndrome & neurotoxicity; mucositis; & neutropenia
- Management:
- Re-medication protocol: Dexamethasone + Diphenhydramine + Famotidine
- Dose reduction / interruption
6. Fluoropyrimidines (5-FU, Capecitabine):
- Hand-foot syndrome & mucositis
- Local extravasation & drug accumulation in capillary beds of palms/soles
- Management:
- Topical emollients, cold compresses and pyridoxine (Vitamin B6)
- Dose reduction/interruption
Drug-Specific Toxicities (Continued):
7. Topoisomerase I (Irinotecan):
- Severe diarrhea
- Early (<24h): Cholinergic syndrome
- Late (>24h): SN-38 metabolite-mediated mucosal injury
- Management:
- Early: Atropine (IV/SC)
- Late: High-dose loperamide (4 mg initially, then 2 mg every 2 hours until clean for 12h)
8. Bleomycin:
- Pulmonary fibrosis
- Oxidative damage leading to collagen deposition due to lack of bleomycin hydrolase in lungs
- Management:
- Restrict cumulative dose to <400 units
- Serial monitoring of PFTs/DLCO
- Discontinue permanently; high-dose corticosteroids
III. Immune-Related Adverse Events (irAEs) - Management
(From the irAE management page)
- Steroid-refractory cases: If no response within 48-72 hours of systemic steroids, introduce targeted immunosuppressants:
- Infliximab (Anti-TNF-α) for severe steroid-refractory colitis
- Mycophenolate Mofetil (MMF) for steroid-refractory hepatitis (Infliximab is avoided in hepatitis due to risks of hepatotoxicity)
- Hormone replacement therapy (Levothyroxine, Hydrocortisone) is mandated permanently for irreversible endocrine toxicities
IV. Immune Checkpoint Inhibitors - Mechanisms
1. CTLA-4 inhibitors
- Mechanism: CTLA-4 operates early during the priming phase of T-cell activation within secondary lymphoid organs. It outcompetes the stimulatory molecule CD28 for binding to CD80/CD86 on Antigen Presenting Cells (APCs)
- Examples: Ipilimumab, Tremelimumab
2. PD-1 inhibitors (Programmed Cell Death Protein 1)
- Mechanism: PD-1 operates during the effector phase within the peripheral tumor microenvironment. Activated T-cells express PD-1, which binds to PD-L1/PD-L2 on tumor cells, sending an inhibitory signal that induces T-cell anergy or apoptosis
- Examples: Pembrolizumab, Nivolumab, Cemiplimab
3. PD-L1 inhibitors (Programmed Death Ligand 1)
- Mechanism: Targets the ligand expressed on the surface of tumor cells and tumor-infiltrating immune cells, preventing its interaction with the PD-1 receptor
- Examples: Atezolizumab, Durvalumab, Avelumab
4. LAG-3 inhibitors (Lymphocyte-Activation Gene 3)
- Mechanism: Blocks an immune checkpoint that suppresses T-cell activation and cytokine secretion, often co-expressed with PD-1 in exhausted T-cells
- Examples: Relatlimab (frequently combined with Nivolumab)
V. Antimicrobial Stewardship Programme (ASP) Interventions & Strategies
ASP Interventions & Strategies:
-
Reporting: Regularly sharing data with prescribers, pharmacists & nurses.
-
Education: Providing updates on AMR & optimal prescribing practices to clinical staff.
-
ASP Interventions & Strategies:
- Front-end Strategy (Pre-authorization): Restricting specific broad-spectrum or reserve antibiotics. Clinicians must obtain approval from the ASP team before prescribing.
- Back-end Strategy (Prospective Audit and Feedback - PAF): The ASP team reviews active antibiotic prescriptions after 48-72 hours to recommend adjustments (escalation, de-escalation, or discontinuation).
- IV-to-Oral switch: Transitioning patients from IV to highly bioavailable oral antimicrobials (e.g. Fluoroquinolones, Linezolid) once clinically stable, reducing line infections and length of stay.
- Dose optimization: Utilizing PK/PD principles (e.g. extended infusions of beta-lactams) to maximize bacterial eradication.
(B) AWaRe Classification
- Developed by the World Health Organization (WHO) as part of the Essential Medicine List. The AWaRe framework categorizes antibiotics into three distinct groups to guide optimal utilization & curb global resistance.
VI. Recent Advances in Oncology
(A) Breast Cancer
1. Therapeutic shift in HER2+ Positive disease: Trastuzumab deruxtecan (T-DXd), a second-generation Antibody-Drug Conjugate (ADC) featuring a highly potent topoisomerase I inhibitor payload and cleavable linker demonstrating a powerful "bystander effect", has expanded into earlier treatment settings. Clinical data has established it as a first-line metastatic option alongside traditional THP (Taxane + Herceptin + Pertuzumab) maintenance strategies, and it is increasingly utilized in neoadjuvant and adjuvant protocols for residual disease.
2. Expansion of CDK 4/6 inhibitors: Cyclin-dependent kinase 4/6 inhibitors (Palbociclib, Ribociclib, Abemaciclib) are firmly established in HR+/HER2- metastatic breast cancer. Recent updates show expanded utility of palbociclib-based regimens in HR+/HER2+ disease when added to standard maintenance endocrine and HER2 therapies, improving progression-free survival (PFS).
3. Targeting Endocrine Resistance: The approval of Elacestrant, a novel oral Selective Estrogen Downregulator (SERD), provides a targeted option for patients with ER+/HER2- metastatic breast cancer harboring ESR1 mutations who progress on first-line endocrine combinations.
4. TROP2-directed ADCs: Sacituzumab govitecan has seen expanded clinical use in both Triple-Negative Breast Cancer (TNBC) and pre-treated hormone receptor-positive/HER2-negative metastatic breast cancer, targeting TROP2 to deliver its SN-38 cytotoxic payload directly to the tumor.
(B) Malignant Melanoma
1. Dual checkpoint inhibition as Frontline Care: Dual immunotherapy combining Relatlimab (LAG-3 inhibitor) and Nivolumab (PD-1 inhibitor) has solidified its position as a preferred first-line treatment standard for advanced or metastatic melanoma, demonstrating superior progression-free survival compared to single-agent anti-PD-1 therapy with a more manageable toxicity profile than the combination of Ipilimumab and Nivolumab.
2. Neoadjuvant immunotherapy: Clinical strategies have pivoted towards utilizing single-agent or dual ICIs in the neoadjuvant (pre-surgical) setting for resectable Stage III melanoma. This approach induces early pathological complete responses (pCR) and generates robust, long-term anti-tumor T-cell clones prior to tumor excision.
3. Advanced AI-driven screenings and diagnostics: Recent clinical integrations leverage deep learning convolutional neural networks (CNNs) alongside 3D Total Body Photography (TBP) and sequential digital dermoscopic imaging to track subtle morphologic variations in high-risk melanocytic naevi, significantly lowering the number needed to biopsy (NNB) ratios in specialized clinics.
4. Targeted Therapy combinations: For BRAF V600 mutated melanomas, triple combinations adding anti-PD-1/PD-L1 agents to BRAF/MEK inhibitor backbone (e.g. Dabrafenib + Trametinib + Spartalizumab) are used to combat early resistance mutations in select patient profiles.
(C) Multiple Myeloma
1. Transition from Triplets to Quadruplets in Frontline Setting: The therapeutic standard for Newly Diagnosed Multiple Myeloma (NDMM) - both transplant-eligible and transplant-ineligible - has transitioned from triplet regimens (e.g. RVd: Lenalidomide, Bortezomib, Dexamethasone) to quadruplet regimens. The integration of anti-CD38 monoclonal antibodies, primarily Daratumumab (or Isatuximab), into frontline backbones (D-RVd) significantly deepens clinical responses, translating to prolonged...
*[Notes end here as captured across all 10 pages]*Here are the 5 additional pages extracted and arranged in order, continuing from where the previous set left off:
Q2 (A) Antibiotic Stewardship Program (ASP)
An Antibiotic Stewardship Program (ASP) is a systematic, organizational approach designed to optimize antimicrobial prescribing, improve patient outcomes, reduce toxicity, and minimize the selection pressure that drives antimicrobial resistance (AMR).
1. Core Objectives
- Clinical optimization: Ensure the right drug is given to the right patient at the right dose, route and duration.
- Safety enhancement: Minimize adverse drug events, notably Clostridioides difficile-associated diarrhea.
- Economic benefit: Lower direct healthcare costs without compromising patient care.
- Public health preservation: Restrict the emergence & spread of multi-drug resistant (MDR) pathogens.
2. Core Elements of an ASP (CDC Guidelines)
- Leadership commitment: Dedication of human, financial, and IT resources.
- Accountability: Appointing a single leader (ideally an infectious disease physician) responsible for outcomes.
- Pharmacy Expertise: Appointing a co-leader pharmacist specialized in infectious diseases.
- Action (Interventions): Implementing specific interventions (e.g. prospective audit & feedback, pre-authorization).
- Tracking: Monitoring antibiotic prescribing patterns & resistance profiles (antibiogram).
3. ASP Interventions & Strategies
- Reporting: Regularly sharing data with prescribers, pharmacists & nurses.
- Education: Providing updates on AMR & optimal prescribing practices to clinical staff.
- Front-end Strategy (Pre-authorization): Restricting specific broad-spectrum or reserve antibiotics. Clinicians must obtain approval from the ASP team before prescribing.
- Back-end Strategy (Prospective Audit and Feedback - PAF): The ASP team reviews active antibiotic prescriptions after 48-72 hours to recommend adjustments (escalation, de-escalation, or discontinuation).
- IV-to-Oral switch: Transitioning patients from IV to highly bioavailable oral antimicrobials (e.g. Fluoroquinolones, Linezolid) once clinically stable, reducing line infections and length of stay.
- Dose optimization: Utilizing PK/PD principles (e.g. extended infusions of beta-lactams) to maximize bacterial eradication.
(B) AWaRe Classification
Developed by the World Health Organization (WHO) as part of the Essential Medicine List. The AWaRe framework categorizes antibiotics into three distinct groups to guide optimal utilization & curb global resistance.
1. ACCESS group
- Characteristics: Antibiotics that exhibit a narrow spectrum of activity, lower resistance potential, and a favourable safety profile. They should be widely available, affordable and quality-assured.
- Clinical Utility: First- or second-choice options for empirical treatment of common infectious syndromes (e.g. community-acquired pneumonia, skin infections).
- Examples: Amoxicillin, Ampicillin, Benzylpenicillin, Cefazolin, Gentamicin, Doxycycline, Metronidazole.
2. WATCH group
- Characteristics: Antibiotics with higher resistance potential or a broader spectrum of activity. They include key agents critically important for human medicine.
- Clinical Utility: Reserved for highly specific indications and used when Access group drugs are ineffective. Their use must be closely monitored to prevent rapid resistance development.
- Examples: Ceftriaxone, Cefotaxime (3rd gen Ceph), Ciprofloxacin, Levofloxacin, Azithromycin, Clarithromycin (Macrolides), Piperacillin-Tazobactam, Meropenem.
3. RESERVE group
- Characteristics: "Last-resort" antibiotics that should be protected and reserved strictly for the treatment of confirmed or highly suspected infections caused by multi-drug resistant (MDR) pathogens.
- Clinical utility: Highly restricted. Their use should be governed by patient-specific ASP pre-authorizations and microbiological confirmation.
- Examples: Colistin, Polymyxin B, Linezolid, Daptomycin, Ceftazidime-Avibactam, Tigecycline.
- Global Target: The WHO specifies a country-level target where at least 60% of all national antibiotic consumption should come from the Access group to promote rational use.
Q3. Immune Checkpoint Inhibitors (ICIs)
ICIs are monoclonal antibodies that disrupt the inhibitory signaling pathways utilized by tumor cells to evade T-cell-mediated immunosurveillance. By blocking these checkpoints, ICIs restore and amplify the host's anti-tumor T-cell responses.
T-cell activation:
- MHC → TCR (Signal 1)
- CD80/86 → CD28 (Signal 2)
- [T-cell kills tumor]
I. Major Classes & Examples
1. CTLA-4 inhibitors (Cytotoxic T-lymphocyte Associated Protein 4):
- Mechanism: CTLA-4 operates early during the priming phase of T-cell activation within secondary lymphoid organs. It outcompetes the stimulatory molecule CD28 for binding to CD80/CD86 on Antigen Presenting Cells (APCs).
- Examples: Ipilimumab, Tremelimumab
2. PD-1 inhibitors (Programmed Cell Death Protein 1):
- Mechanism: PD-1 operates during the effector phase within the peripheral tumor microenvironment. Activated T-cells express PD-1, which binds to PD-L1/PD-L2 on tumor cells, sending an inhibitory signal that induces T-cell anergy or apoptosis.
- Examples: Pembrolizumab, Nivolumab, Cemiplimab
3. PD-L1 inhibitors (Programmed Death Ligand 1):
- Mechanism: Targets the ligand expressed on the surface of tumor cells and tumor-infiltrating immune cells, preventing its interaction with the PD-1 receptor.
- Examples: Atezolizumab, Durvalumab, Avelumab
4. LAG-3 inhibitors (Lymphocyte-Activation Gene 3):
- Mechanism: Blocks an immune checkpoint that suppresses T-cell activation and cytokine secretion, often co-expressed with PD-1 in exhausted T-cells.
- Examples: Relatlimab (frequently combined with Nivolumab)
Immune-Related Adverse Events (irAEs)
Because ICTs remove physiological "brakes" on the immune system, they can trigger systemic, autoimmune-like toxicities called immune-related adverse events (irAEs). These can affect almost any organ system:
- Dermatological: Maculopapular rash, pruritus, vitiligo, and rare life-threatening conditions like Stevens-Johnson Syndrome (SJS).
- Gastrointestinal: Immune-mediated colitis, presenting as severe diarrhea and bowel perforation.
- Endocrine: Hypophysitis (anterior pituitary inflammation), thyroiditis (hypothyroidism or hyperthyroidism) and Type 1 Diabetes mellitus due to insulitis.
- Pulmonary: Pneumonitis, manifesting as non-productive cough, dyspnea, and hypoxia.
- Hepatic: Autoimmune hepatitis (elevated transaminases).
Management of irAEs:
- Grade 1 (mild): Continue ICI therapy with close clinical monitoring; treat symptoms topically (e.g. topical steroids for mild rash).
- Grade 2 (moderate): Hold the ICI; Initiate oral Prednisone (0.5-1 mg/kg/day). Resume therapy once symptoms resolve to Grade ≤1.
- Grade 3/4 (severe/life-threatening): Permanently discontinue the ICI; Hospitalize the patient and initiate high-dose intravenous methylprednisolone (1-2 mg/kg/day).
- Steroid-refractory cases: If no response within 48-72 hours of systemic steroids, introduce targeted immunosuppressants:
- Infliximab (Anti-TNF-α) for severe steroid-refractory colitis
- Mycophenolate Mofetil (MMF) for steroid-refractory hepatitis (Infliximab is avoided in hepatitis due to risks of hepatotoxicity)
- Hormone replacement therapy (Levothyroxine, Hydrocortisone) is mandated permanently for irreversible endocrine toxicities.
Recent Advances in Oncology (Continued)
(C) Multiple Myeloma (continued)
...progression-free survival and sustained Minimal Residual Disease (MRD) negativity.
2. T-cell redirecting bispecific antibodies (BiTEs): Bispecific T-cell engagers (BiTEs) have transformed the treatment of relapsed or refractory multiple myeloma (RRMM). Agents such as Teclistamab and Elranatamab (targeting BCMA on plasma cells and CD3 on T-cells) and Talquetamab (targeting GPRC5D and CD3) dual-bind to bypass traditional MHC activation pathways, orchestrating direct T-cell-mediated destruction of malignant plasma cells.
3. Second-Line Integration of CAR-T-cell therapies: B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell therapies, specifically Ciltacabtagene autoleucel (Cilta-cel) and Idecabtagene vicleucel (Ide-cel), have migrated from late-stage salvage therapies into earlier lines of treatment (e.g. after 1-3 prior lines of therapy), demonstrating unprecedented response rates in functional relapses.
4. Next-Generation Cereblon E3 Ligase Modulators (CELMoDs): Novel agents like Iberdomide and Mezigdomide are undergoing advanced assessment. Developed to possess significantly higher binding affinity for Cereblon than standard IMiDs (Lenalidomide/Pomalidomide), they induce rapid degradation of the Ikaros and Aiolos transcription factors, demonstrating clear activity in triple-class refractory myeloma.
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Class specific toxicity and their management Based on this classification
Here is the complete Class-Specific Toxicity and Management table based exactly on the classification shown in your textbook diagrams:
Class-Specific Toxicities & Management of Anticancer Drugs
ANTICANCER DRUGS (1) — Cytotoxic Drugs (1)
1. Alkylating Agents
Nitrogen Mustards (Cyclophosphamide, Ifosfamide, Melphalan, Chlorambucil, Mechlorethamine, Bendamustine)
| Toxicity | Mechanism | Management |
|---|---|---|
| Haemorrhagic cystitis (Cyclophosphamide, Ifosfamide) | Toxic metabolite acrolein accumulates in bladder | MESNA (binds & detoxifies acrolein); vigorous IV hydration; frequent voiding |
| Myelosuppression | Direct bone marrow suppression | G-CSF support; dose reduction |
| Gonadal toxicity / infertility | DNA alkylation of germ cells | Sperm/oocyte cryopreservation before therapy |
| Secondary malignancies (AML/MDS) | Mutagenic DNA crosslinking | Long-term surveillance |
| SIADH (Cyclophosphamide) | Direct renal tubular effect | Fluid restriction; monitor serum Na⁺ |
| Pulmonary fibrosis (Melphalan, Busulfan) | Oxidative lung damage | PFT monitoring; discontinue drug |
Nitrosoureas (Carmustine, Lomustine)
| Toxicity | Mechanism | Management |
|---|---|---|
| Delayed myelosuppression (nadir at 4-6 weeks) | Slow alkylation of marrow stem cells | Prolonged monitoring of CBC; delay next cycle |
| Pulmonary fibrosis | Oxidative lung injury | Cumulative dose limit; PFT monitoring |
| Hepatotoxicity | Direct hepatocellular damage | LFT monitoring |
| CNS toxicity (Carmustine - high dose) | BBB penetration | Neurological monitoring |
Alkylsulfonate — Busulfan
| Toxicity | Mechanism | Management |
|---|---|---|
| Pulmonary fibrosis ("Busulfan lung") | Oxidative damage | PFT monitoring; discontinue |
| Hyperpigmentation | Melanin stimulation | Cosmetic; dose reduction |
| Seizures (high-dose conditioning) | CNS accumulation | Prophylactic phenytoin/levetiracetam |
| Severe myelosuppression | Direct marrow ablation | Used intentionally in HSCT conditioning |
Triazines (Dacarbazine, Temozolomide)
| Toxicity | Mechanism | Management |
|---|---|---|
| Nausea/Vomiting (severe with Dacarbazine) | Central & peripheral serotonin activation | Ondansetron + Dexamethasone pre-treatment |
| Myelosuppression | DNA methylation of marrow cells | CBC monitoring; G-CSF |
| Flu-like syndrome (Dacarbazine) | Cytokine release | Paracetamol; supportive care |
| Fatigue (Temozolomide) | CNS effect | Dose scheduling; supportive care |
Ethylenimine (Thiotepa, Altretamine)
| Toxicity | Mechanism | Management |
|---|---|---|
| Myelosuppression | Bone marrow suppression | CBC monitoring; G-CSF |
| Neurotoxicity (Altretamine) | Peripheral neuropathy | Dose reduction; Vitamin B6 |
| Mucositis | Mucosal DNA damage | Oral hygiene; topical agents |
Methyl hydrazine (Procarbazine)
| Toxicity | Mechanism | Management |
|---|---|---|
| MAO inhibition - hypertensive crisis | Procarbazine inhibits MAO | Avoid tyramine-rich foods; avoid SSRIs/TCAs |
| Myelosuppression | Bone marrow suppression | CBC monitoring |
| Disulfiram-like reaction | Inhibits aldehyde dehydrogenase | Strict alcohol avoidance |
| Neurotoxicity | CNS penetration | Neurological monitoring |
2. Platinum Coordination Complexes (Cisplatin, Carboplatin, Oxaliplatin)
| Toxicity | Drug | Mechanism | Management |
|---|---|---|---|
| Nephrotoxicity (dose-limiting) | Cisplatin >> Carboplatin | Platinum accumulation in proximal tubules → tubular necrosis | Aggressive pre/post IV hydration with normal saline; Mannitol diuresis; Amifostine (cytoprotectant) |
| Severe emesis | Cisplatin (most emetogenic drug) | Central & peripheral 5-HT3, NK1, dopamine activation | Triple antiemetic: Ondansetron + Aprepitant + Dexamethasone ± Olanzapine |
| Peripheral neuropathy | Cisplatin, Oxaliplatin | Dorsal root ganglion accumulation; sensory neuron damage | Dose reduction; Duloxetine (for established neuropathy) |
| Ototoxicity (irreversible) | Cisplatin | Cochlear hair cell destruction | Baseline & serial audiometry; cumulative dose limits |
| Hypomagnesaemia / Electrolyte loss | Cisplatin | Tubular wasting | Magnesium/potassium supplementation |
| Cold-triggered dysesthesia | Oxaliplatin | Transient Na⁺ channel dysfunction in cold | Warn patient; avoid cold drinks/exposure; resolves spontaneously |
| Myelosuppression (dose-limiting) | Carboplatin | Bone marrow suppression | CBC monitoring; dose by AUC (Calvert formula) |
| Allergic reactions | Carboplatin (after multiple cycles) | IgE-mediated | Premedication with steroids + antihistamines; desensitization |
3. Antimetabolites
Folate Antagonists (Methotrexate, Pemetrexed)
| Toxicity | Mechanism | Management |
|---|---|---|
| Mucositis / Stomatitis | DHFR inhibition → ↓ thymidylate → mucosal cell death | Leucovorin (folinic acid) rescue after high-dose MTX; oral hygiene |
| Myelosuppression | Folate depletion → impaired DNA synthesis in marrow | Leucovorin rescue; G-CSF; dose reduction |
| Hepatotoxicity (chronic, cirrhosis) | Methotrexate polyglutamate accumulation in hepatocytes | LFT monitoring; liver biopsy if cumulative dose high; avoid alcohol |
| Nephrotoxicity / MTX precipitation | MTX crystallizes in renal tubules at low pH | Urine alkalinization (NaHCO₃); high-volume hydration; MTX serum level monitoring |
| Pulmonary toxicity ("MTX pneumonitis") | Hypersensitivity / direct toxicity | Discontinue; high-dose corticosteroids |
| Neurotoxicity (intrathecal MTX) | Direct CNS irritation | Leucovorin; dose adjustment |
| Folic acid supplementation (Pemetrexed) | Prevents folate depletion | Mandatory: Folic acid daily + Vitamin B12 injection before every cycle + Dexamethasone premedication |
Pyrimidine Antagonists (5-FU, Capecitabine, Cytarabine, Gemcitabine, Doxyfluridine)
| Toxicity | Drug | Mechanism | Management |
|---|---|---|---|
| Hand-Foot Syndrome (palmar-plantar erythrodysesthesia) | 5-FU, Capecitabine | Drug accumulation in eccrine glands of palms/soles | Pyridoxine (Vit B6); topical emollients (urea cream); dose reduction/interruption |
| Mucositis / Diarrhea | 5-FU (infusional) | Mucosal epithelial DNA damage | Oral hygiene; Loperamide for diarrhea; dose reduction |
| Cardiotoxicity (coronary vasospasm) | 5-FU | Endothelial toxicity → coronary vasospasm | Discontinue; Nitrates + Calcium channel blockers; switch to alternative |
| DPD deficiency - severe toxicity | 5-FU, Capecitabine | Absent DPD enzyme → drug accumulation | Screen DPD genotype (DPYD) before treatment; reduce dose in heterozygotes |
| Cerebellar toxicity | 5-FU | Unknown | Discontinue; supportive care |
| Myelosuppression | Cytarabine, Gemcitabine | Bone marrow suppression | CBC monitoring; G-CSF |
| Cytarabine syndrome | Cytarabine | Cytokine release | Prophylactic corticosteroids |
| Pulmonary toxicity / Radiation recall | Gemcitabine | Capillary leak; inflammatory | Steroids; discontinue |
| Flu-like symptoms | Gemcitabine | Cytokine release | Paracetamol |
Purine Antagonists (6-MP, 6-Thioguanine, Azathioprine, Fludarabine)
| Toxicity | Mechanism | Management |
|---|---|---|
| Myelosuppression | Purine synthesis inhibition | CBC monitoring; dose reduction |
| Hepatotoxicity / Veno-occlusive disease (6-TG) | Hepatic sinusoidal injury | LFT monitoring; discontinue |
| Immunosuppression / Opportunistic infections (Fludarabine) | T-cell depletion | PCP prophylaxis (Cotrimoxazole); CMV monitoring; irradiated blood products (to prevent TA-GvHD) |
| TPMT deficiency → severe toxicity | Absent TPMT enzyme → 6-MP/Aza accumulation | Screen TPMT genotype before treatment; dose reduce in low activity |
| Drug interaction (Allopurinol + 6-MP) | Allopurinol inhibits xanthine oxidase → ↑ 6-MP levels | Reduce 6-MP dose by 75% if co-administered with allopurinol |
| Autoimmune hemolysis (Fludarabine) | Immune activation | Transfusion support; steroids |
ANTICANCER DRUGS (2) — Cytotoxic Drugs (2)
4. Microtubule Damaging Agents
Vinca Alkaloids (Vincristine, Vinblastine, Vinorelbine)
| Toxicity | Mechanism | Management |
|---|---|---|
| Peripheral neuropathy (dose-limiting for Vincristine) | Inhibit tubulin polymerization → axonal microtubule disruption → axonal transport failure | Dose reduction (cumulative dose cap ~2 mg/dose for Vincristine); Duloxetine; Gabapentin; Vitamin B6 |
| Autonomic neuropathy (constipation, paralytic ileus, urinary retention) | Autonomic nerve fiber involvement | Prophylactic laxatives (lactulose/senna); bowel monitoring |
| SIADH (Vincristine) | Hypothalamic/posterior pituitary toxicity | Fluid restriction; monitor Na⁺ |
| Myelosuppression (Vinblastine > Vincristine) | Bone marrow suppression | CBC monitoring; G-CSF |
| Severe tissue necrosis if extravasated | Vesicant property | Use central line; hyaluronidase for extravasation |
| FATAL if given intrathecally | Direct spinal cord necrosis | Never administer intrathecally — must be dispensed in mini-bag (100 mL) to prevent IT administration |
Taxanes (Paclitaxel, Docetaxel)
| Toxicity | Mechanism | Management |
|---|---|---|
| Hypersensitivity reactions (Paclitaxel) | Cremophor EL vehicle triggers mast cell degranulation → histamine release | Mandatory premedication: Dexamethasone + Diphenhydramine + H2-blocker (Ranitidine/Famotidine) 30 min before infusion |
| Peripheral neuropathy | Microtubule stabilization → axonal dysfunction | Dose reduction; Duloxetine; Gabapentin |
| Myelosuppression (Docetaxel > Paclitaxel) | Bone marrow suppression | G-CSF; dose reduction |
| Fluid retention / Edema (Docetaxel) | Capillary leak syndrome | Dexamethasone 8 mg BD for 3 days starting 1 day before (premedication); diuretics |
| Nail changes / Onycholysis | Direct toxicity to nail bed | Frozen gloves/socks during infusion; topical care |
| Bradycardia / Heart block | Cardiac conduction effect | Cardiac monitoring during infusion |
Estramustine
| Toxicity | Mechanism | Management |
|---|---|---|
| Thromboembolic events | Estrogen component → coagulation activation | Anti-thrombotic prophylaxis; monitor |
| Gynecomastia / Cardiovascular | Estrogenic effects | Monitoring; dose adjustment |
5. Topoisomerase Inhibitors
Topoisomerase-2 Inhibitor — Etoposide
| Toxicity | Mechanism | Management |
|---|---|---|
| Myelosuppression (dose-limiting) | Bone marrow suppression | CBC monitoring; G-CSF |
| Secondary AML (t-AML with 11q23 translocation) | Topoisomerase II inhibition → MLL gene rearrangement | Cumulative dose awareness; long-term haematological surveillance |
| Hypersensitivity (rapid infusion) | Vehicle (polysorbate 80) | Slow infusion rate (>30-60 min); premedication |
| Mucositis | Mucosal epithelial damage | Oral hygiene; supportive care |
Topoisomerase-1 Inhibitors (Topotecan, Irinotecan)
| Toxicity | Drug | Mechanism | Management |
|---|---|---|---|
| Myelosuppression (dose-limiting) | Topotecan >> Irinotecan | Bone marrow S-phase toxicity | CBC monitoring; G-CSF; dose reduction |
| Severe diarrhea - Early (<24h) | Irinotecan | Cholinergic syndrome (SN-38 inhibits AChE) - cramping, flushing, hypersalivation, diarrhea | Atropine IV/SC 0.25-1 mg |
| Severe diarrhea - Late (>24h) | Irinotecan | Active metabolite SN-38 mediates mucosal injury | High-dose Loperamide: 4 mg stat, then 2 mg every 2h until diarrhea-free for 12h |
| UGT1A1 polymorphism | Irinotecan | Reduced SN-38 glucuronidation → toxicity (UGT1A1*28) | Screen UGT1A1 genotype; reduce starting dose in *28 homozygotes |
6. Antibiotics (Cytotoxic)
Anthracyclines (Doxorubicin, Daunorubicin, Epirubicin, Idarubicin, Mitoxantrone)
| Toxicity | Mechanism | Management |
|---|---|---|
| Cardiotoxicity - Acute (arrhythmias, ECG changes) | Direct myocardial inflammation | ECG monitoring; usually reversible |
| Cardiotoxicity - Chronic (dilated cardiomyopathy) | Free radical (ROS) generation + Topoisomerase IIβ inhibition in cardiomyocytes → cardiomyocyte apoptosis | Cumulative dose cap: Doxorubicin <450-550 mg/m²; Dexrazoxane (iron chelator - cardioprotective); baseline + serial ECHO/MUGA (LVEF monitoring); liposomal formulation reduces cardiotoxicity |
| Severe tissue necrosis if extravasated | Vesicant | Central line preferred; Dexrazoxane IV within 6h of extravasation; cold compresses |
| Myelosuppression | Bone marrow suppression | CBC monitoring; G-CSF |
| Alopecia | Rapidly dividing hair follicle cells | Scalp cooling during infusion; cosmetic |
| Secondary AML | Topoisomerase II inhibition | Cumulative dose monitoring; surveillance |
| Red/orange urine discolouration | Drug excretion in urine | Reassure patient (harmless) |
Bleomycin
| Toxicity | Mechanism | Management |
|---|---|---|
| Pulmonary fibrosis (dose-limiting, potentially fatal) | Oxidative DNA strand breaks → collagen deposition; lungs lack bleomycin hydrolase enzyme | Cumulative dose limit <400 units; serial PFTs/DLCO before each cycle; permanently discontinue if pulmonary toxicity confirmed; high-dose corticosteroids |
| Mucocutaneous toxicity (flagellate dermatitis, hyperpigmentation) | Direct skin toxicity | Topical emollients; dose reduction |
| Fever/chills (acute) | Cytokine release | Paracetamol; test dose recommended |
| Hypersensitivity/anaphylaxis (rare - lymphoma patients) | IgE-mediated | Test dose 1-2 units IM before first full dose in lymphoma patients; resuscitation facilities on standby |
| Minimal myelosuppression | Lacks significant marrow toxicity | Not dose-limiting for bone marrow |
Actinomycin D (Dactinomycin)
| Toxicity | Mechanism | Management |
|---|---|---|
| Myelosuppression | Bone marrow suppression | CBC monitoring |
| Mucositis / GI toxicity | Mucosal damage | Oral hygiene; supportive care |
| Hepatic veno-occlusive disease (in children) | Hepatic sinusoidal injury | LFT monitoring; dose reduction |
| Radiation recall reaction | Re-activates radiation damage in previously irradiated tissue | Avoid in previously irradiated fields; topical steroids |
Mitomycin C
| Toxicity | Mechanism | Management |
|---|---|---|
| Myelosuppression (cumulative, delayed) | Bone marrow suppression | Serial CBC; cumulative dose awareness |
| Haemolytic Uremic Syndrome (HUS) | Endothelial microangiopathy | Plasmapheresis; discontinue drug |
| Pulmonary toxicity | Oxidative lung injury | PFT monitoring; steroids; discontinue |
7. Miscellaneous Cytotoxics
Hydroxyurea
| Toxicity | Management |
|---|---|
| Myelosuppression, leg ulcers, macrocytosis | CBC monitoring; wound care; folate supplementation |
L-Asparaginase
| Toxicity | Management |
|---|---|
| Hypersensitivity/anaphylaxis | Test dose; resuscitation ready; switch to Pegaspargase or Erwinia asparaginase |
| Pancreatitis | Monitor amylase/lipase; discontinue if severe |
| Coagulopathy (↓ fibrinogen, AT-III) | Fresh frozen plasma; coagulation monitoring |
| Hepatotoxicity | LFT monitoring |
| CNS thrombosis or hemorrhage | Coagulation factor replacement |
Tretinoin (ATRA - All-trans Retinoic Acid)
| Toxicity | Management |
|---|---|
| Differentiation syndrome (APL) - fever, pulmonary infiltrates, weight gain, hypotension | High-dose dexamethasone 10 mg IV BD immediately; consider temporary ATRA interruption |
| Hyperlipidaemia, pseudotumour cerebri | Lipid monitoring; dose reduction |
Arsenic Trioxide
| Toxicity | Management |
|---|---|
| QTc prolongation / Torsades de Pointes | Baseline ECG; correct electrolytes (K⁺, Mg²⁺); avoid QT-prolonging drugs; ECG monitoring during therapy |
| Differentiation syndrome (similar to ATRA) | High-dose dexamethasone |
| Peripheral neuropathy | Dose reduction; monitoring |
ANTICANCER DRUGS (3) — Targeted Drugs
8. BCR-ABL Tyrosine Kinase Inhibitors (Imatinib, Dasatinib, Nilotinib)
| Toxicity | Drug | Mechanism | Management |
|---|---|---|---|
| Fluid retention / Edema / Pleural effusion | Imatinib, Dasatinib | PDGFR inhibition → fluid accumulation | Diuretics; dose reduction; thoracocentesis if needed |
| Hepatotoxicity | All TKIs | Direct hepatocellular damage | LFT monitoring; dose hold/reduction |
| QTc prolongation | Nilotinib >> Dasatinib | hERG channel blockade | Baseline ECG; correct electrolytes; avoid QT-prolonging drugs |
| Arterial occlusive events (PAD, MI, stroke) | Nilotinib, Ponatinib | Vascular endothelial toxicity | Cardiovascular risk assessment; switch to safer TKI if needed |
| Pulmonary arterial hypertension | Dasatinib | Pulmonary vascular toxicity | Echocardiogram monitoring; discontinue if confirmed |
| Myelosuppression | All | Off-target marrow suppression | CBC monitoring; dose interruption |
| Nausea / GI toxicity | Imatinib | GI irritation | Take with food; antacids |
| Muscle cramps | Imatinib | Electrolyte imbalance | Magnesium/electrolyte supplementation |
| Hyperglycaemia | Nilotinib | Pancreatic beta-cell toxicity | Glucose monitoring; diabetes management |
9. EGF/HER Receptor Inhibitors (Gefitinib, Erlotinib, Cetuximab, Trastuzumab, Lapatinib)
| Toxicity | Drug | Mechanism | Management |
|---|---|---|---|
| Acneiform rash (dose-dependent - marker of efficacy) | Gefitinib, Erlotinib, Cetuximab, Lapatinib | EGFR inhibition in skin | Topical antibiotics (clindamycin); oral doxycycline; topical steroids; moisturizers |
| Interstitial lung disease / Pneumonitis | Gefitinib, Erlotinib | Direct alveolar toxicity | Discontinue drug; high-dose corticosteroids |
| Diarrhea | All EGFR inhibitors | Loss of EGFR-mediated intestinal regulation | Loperamide; dose reduction; adequate hydration |
| Cardiotoxicity / Cardiomyopathy | Trastuzumab (reversible) | HER2 blockade in cardiomyocytes (unlike anthracyclines - not free radical mediated, hence reversible) | Baseline + serial ECHO (LVEF) every 3 months; hold if LVEF drops >10% or <50%; do NOT combine with anthracyclines concurrently; generally recovers on discontinuation |
| Hypomagnesaemia | Cetuximab | EGFR inhibition in renal tubules → Mg²⁺ wasting | Magnesium supplementation (oral/IV) |
| Infusion reactions | Cetuximab, Trastuzumab | IgE / complement activation | Premedication (antihistamines + steroids); slow infusion rate |
| Hepatotoxicity | Lapatinib | Direct hepatocellular toxicity | LFT monitoring |
10. Angiogenesis Inhibitors (Bevacizumab, Sunitinib, Sorafenib)
| Toxicity | Mechanism | Management |
|---|---|---|
| Hypertension (class effect) | VEGF inhibition → loss of NO-mediated vasodilation → vasoconstriction | Antihypertensives (ACE inhibitors/ARBs preferred); regular BP monitoring; dose reduction |
| Impaired wound healing / Fistula / GI perforation | VEGF required for angiogenesis in wound healing | Withhold Bevacizumab 4-6 weeks before/after major surgery |
| Thromboembolic events (arterial) | Endothelial dysfunction | Anti-thrombotic therapy; risk stratification |
| Bleeding / Haemoptysis | Impaired platelet plug formation + vessel wall integrity | Avoid in CNS metastases/recent haemorrhage; withhold if bleeding |
| Proteinuria / Nephrotoxicity | VEGF inhibition in glomerulus → podocyte injury | Urine protein:creatinine ratio monitoring; hold if ≥2g/24h proteinuria |
| Hand-Foot Skin Reaction (Sunitinib, Sorafenib) | Accumulation in pressure areas → keratinocyte damage | Urea-based creams; dose reduction; avoid pressure/friction |
| Hypothyroidism (Sunitinib) | Thyroid gland vascular damage | TFT monitoring every cycle; levothyroxine if needed |
| QTc prolongation (Sunitinib, Sorafenib) | hERG channel blockade | ECG monitoring; electrolyte correction |
| Hepatotoxicity (Sorafenib) | Direct hepatocellular damage | LFT monitoring |
11. Proteasome Inhibitor — Bortezomib
| Toxicity | Mechanism | Management |
|---|---|---|
| Peripheral neuropathy (dose-limiting) | Proteasome inhibition in dorsal root ganglia neurons | Switch to subcutaneous (SC) administration (significantly reduces neuropathy vs IV); weekly dosing instead of twice-weekly; dose reduction; Duloxetine/Gabapentin |
| Herpes Zoster reactivation | Immunosuppression → VZV reactivation | Mandatory antiviral prophylaxis: Acyclovir/Valacyclovir throughout treatment |
| Thrombocytopenia | Direct megakaryocyte toxicity | Platelet monitoring; dose reduction |
| Orthostatic hypotension | Autonomic neuropathy | Adequate hydration; support stockings; fludrocortisone |
| GI toxicity (nausea, diarrhea, constipation) | GI autonomic nerve disruption | Antiemetics; laxatives; loperamide |
12. Immunomodulatory Imides / IMiDs (Thalidomide, Lenalidomide)
| Toxicity | Mechanism | Management |
|---|---|---|
| Teratogenicity (phocomelia - limb defects) | Inhibition of angiogenesis in fetal limb buds | Strict REMS program (Risk Evaluation and Mitigation Strategy); mandatory pregnancy testing; two forms of contraception; men must use condoms |
| Deep Vein Thrombosis / Pulmonary Embolism | Procoagulant state + endothelial activation | Mandatory thromboprophylaxis: Aspirin (low-risk) or LMWH/warfarin (high-risk); risk-stratify all patients |
| Peripheral neuropathy (Thalidomide > Lenalidomide) | Axonal degeneration | Dose reduction; discontinue Thalidomide; Gabapentin |
| Myelosuppression (Lenalidomide > Thalidomide) | Bone marrow suppression | CBC monitoring; dose reduction; G-CSF |
| Sedation / Constipation (Thalidomide) | CNS/autonomic effects | Night-time dosing; laxatives |
| Rash (Lenalidomide) | Immune activation | Antihistamines; dose reduction; steroids |
| Secondary malignancies (MDS/AML) | Genomic instability | Long-term surveillance |
ANTICANCER DRUGS (4) — Hormonal Drugs
13. SERMs (Tamoxifen, Toremifene)
| Toxicity | Mechanism | Management |
|---|---|---|
| Endometrial cancer (Tamoxifen) | Partial estrogen agonism on uterine endometrium | Annual gynecological review; report abnormal bleeding; consider switching to Aromatase inhibitor after 5 years |
| Thromboembolic events (DVT/PE) | Estrogen agonist effect on coagulation | Thromboprophylaxis in high-risk patients; withhold perioperatively |
| Hot flushes / Menopausal symptoms | Estrogen antagonism | Venlafaxine; Gabapentin; lifestyle measures (avoid HRT - stimulates breast cancer) |
| Ocular toxicity (retinopathy, cataracts) | Drug accumulation in retina | Annual ophthalmological exam |
| Increased BMD (bone protective) | Estrogen agonism on bone | Beneficial effect |
14. SER-Down Regulator — Fulvestrant (+ Elacestrant)
| Toxicity | Mechanism | Management |
|---|---|---|
| Injection site reactions | IM injection (gluteal) | Rotate injection sites; local anaesthetic |
| Hot flushes / Menopausal symptoms | Complete ER antagonism | Venlafaxine; Gabapentin |
| Bone loss / Osteoporosis | Loss of estrogenic bone protection | Baseline DEXA scan; bisphosphonates/denosumab; calcium + Vitamin D |
| Hepatotoxicity | Direct hepatic metabolism | LFT monitoring |
15. Aromatase Inhibitors (Letrozole, Anastrozole, Exemestane)
| Toxicity | Mechanism | Management |
|---|---|---|
| Arthralgia / Myalgia ("AI-associated musculoskeletal syndrome") | Estrogen deprivation → joint inflammation | Vitamin D; NSAIDs; duloxetine; switch between AIs; dose reduction |
| Bone loss / Osteoporosis / Fractures (most important long-term toxicity) | Severe estrogen deprivation → osteoclast activation | Baseline DEXA scan; bisphosphonates (Zoledronic acid) or Denosumab; Calcium + Vit D supplementation |
| Hot flushes / Menopausal symptoms | Profound estrogen depletion | Venlafaxine; Gabapentin; acupuncture |
| Hyperlipidaemia | Loss of estrogen's lipid-protective effects | Lipid monitoring; statins if needed |
| Cardiovascular events | Loss of cardioprotective estrogen effects | Cardiovascular risk monitoring |
16. Glucocorticoids (Prednisolone)
| Toxicity | Management |
|---|---|
| Hyperglycaemia | Blood glucose monitoring; insulin/OHA adjustment |
| Osteoporosis | Calcium + Vit D; bisphosphonates for long-term use |
| Immunosuppression / Infections | PCP prophylaxis; vaccination review |
| Cushingoid features, weight gain, fluid retention | Lowest effective dose; salt restriction |
| Adrenal insufficiency on withdrawal | Gradual dose tapering; never stop abruptly |
17. Antiandrogens (Flutamide, Bicalutamide)
| Toxicity | Mechanism | Management |
|---|---|---|
| Hepatotoxicity (Flutamide - potentially fatal) | Direct hepatocellular toxicity | LFT monitoring every month for Flutamide; switch to Bicalutamide (safer hepatic profile) |
| Gynecomastia / Breast tenderness | Androgen blockade → relative estrogen dominance | Prophylactic low-dose breast radiotherapy; Tamoxifen |
| Hot flushes | Androgen depletion | Venlafaxine; Cyproterone acetate |
| Diarrhea (Flutamide) | GI motility effects | Loperamide; dose reduction |
18. GnRH Analogues (Nafarelin, Leuprorelin, Triptorelin)
| Toxicity | Mechanism | Management |
|---|---|---|
| Tumour flare (initial 1-2 weeks) | Initial LH/FSH surge before downregulation → testosterone surge | Co-administer antiandrogen (Bicalutamide) for first 2-4 weeks to block flare |
| Hot flushes / Menopausal symptoms | Castrate testosterone levels | Venlafaxine; Medroxyprogesterone acetate |
| Osteoporosis | Prolonged androgen/estrogen deprivation | Baseline DEXA; bisphosphonates; Calcium + Vit D |
| Erectile dysfunction / Loss of libido | Castrate testosterone levels | PDE5 inhibitors; patient counselling |
| Metabolic syndrome / Dyslipidaemia | Testosterone deficiency → metabolic dysregulation | Lipid monitoring; exercise; metformin |
19. CD20 Inhibitor — Rituximab
| Toxicity | Mechanism | Management |
|---|---|---|
| Infusion-related reactions (fever, rigors, hypotension - most common) | Cytokine release from rapid B-cell lysis (Cytokine Release Syndrome) | Premedicate: Paracetamol + Antihistamine + Hydrocortisone; slow infusion rate (start at 50 mg/h); stop infusion if severe |
| Hepatitis B reactivation (potentially fatal) | Immunosuppression → viral reactivation | Screen all patients for HBsAg and anti-HBc before treatment; prophylactic Entecavir/Tenofovir in HBsAg+/anti-HBc+ patients throughout treatment and 12 months after |
| PML (Progressive Multifocal Leukoencephalopathy) | JC virus reactivation due to profound immunosuppression | JC virus antibody testing; MRI brain if neurological symptoms; no specific treatment - discontinue Rituximab |
| Late-onset neutropenia | Bone marrow B-cell precursor depletion | CBC monitoring for up to 6 months post-treatment |
| Hypogammaglobulinaemia | B-cell depletion → reduced immunoglobulin production | IgG monitoring; IV immunoglobulin (IVIG) replacement if recurrent infections |
Key exam tip: The three drugs requiring mandatory genotype screening before use are: 5-FU/Capecitabine (DPYD), 6-MP/Azathioprine (TPMT), and Irinotecan (UGT1A1). The three drugs most likely to cause secondary AML are: Alkylating agents, Etoposide, and Anthracyclines.
Very short note
Class-Specific Toxicity & Management — Quick Notes
CYTOTOXIC DRUGS (1)
Alkylating Agents
- Cyclophosphamide/Ifosfamide → Haemorrhagic cystitis → MESNA + hydration
- All alkylators → Myelosuppression → G-CSF
- Busulfan → Pulmonary fibrosis + Seizures (high dose) → PFT monitoring + phenytoin prophylaxis
- Procarbazine → MAO inhibition + Disulfiram reaction → avoid tyramine & alcohol
Platinum Complexes
- Cisplatin → Nephrotoxicity + Ototoxicity + Severe emesis → IV hydration + Mannitol + Triple antiemetic (Ondansetron + Aprepitant + Dex)
- Carboplatin → Myelosuppression (dose-limiting) → dose by AUC
- Oxaliplatin → Cold-triggered neuropathy → avoid cold exposure
Antimetabolites
- MTX → Mucositis + Nephrotoxicity → Leucovorin rescue + urine alkalinization
- Pemetrexed → Folate deficiency toxicity → Folic acid + Vit B12 mandatory pretreatment
- 5-FU/Capecitabine → Hand-Foot Syndrome + DPD deficiency risk → Pyridoxine + screen DPYD gene
- 5-FU → Coronary vasospasm → discontinue; nitrates
- Irinotecan → Early diarrhea (cholinergic) → Atropine; Late diarrhea (SN-38) → high-dose Loperamide; screen UGT1A1
- 6-MP/Azathioprine → Toxicity if TPMT deficient → screen TPMT; reduce dose 75% with allopurinol
- Fludarabine → Severe immunosuppression → PCP prophylaxis + irradiated blood products
CYTOTOXIC DRUGS (2)
Vinca Alkaloids
- Vincristine → Peripheral + autonomic neuropathy (constipation) → dose cap 2 mg; prophylactic laxatives
- FATAL if given intrathecally → dispense in mini-bag only
- Vinblastine → Myelosuppression > neuropathy
Taxanes
- Paclitaxel → Hypersensitivity (Cremophor) → premedicate Dex + Diphenhydramine + H2-blocker
- Docetaxel → Fluid retention → Dexamethasone 3-day premedication
- Both → Peripheral neuropathy + Myelosuppression
Topoisomerase-2 (Etoposide)
- Myelosuppression + Secondary AML (11q23) → cumulative dose monitoring
Topoisomerase-1 (Irinotecan/Topotecan)
- (See above under Antimetabolites for Irinotecan)
- Topotecan → Myelosuppression (dose-limiting)
Antibiotics
- Anthracyclines → Cardiotoxicity (dilated CMP) → dose cap (<450 mg/m²) + Dexrazoxane + serial ECHO
- Bleomycin → Pulmonary fibrosis → dose cap <400 units + serial PFTs/DLCO + permanently discontinue
- Mitomycin C → HUS + delayed myelosuppression → plasmapheresis for HUS
- Actinomycin D → Radiation recall + hepatic VOD in children
Miscellaneous
- L-Asparaginase → Anaphylaxis + Pancreatitis + Coagulopathy → test dose; FFP; monitor enzymes
- ATRA → Differentiation syndrome → high-dose Dexamethasone IV immediately
- Arsenic trioxide → QTc prolongation → ECG monitoring + correct K⁺/Mg²⁺
TARGETED DRUGS
BCR-ABL TKIs (Imatinib/Dasatinib/Nilotinib)
- Imatinib → Edema + nausea + muscle cramps → diuretics; take with food; Mg²⁺
- Dasatinib → Pleural effusion + Pulmonary arterial hypertension → Echo monitoring; discontinue
- Nilotinib → QTc prolongation + Arterial occlusive events + Hyperglycaemia → ECG; cardiovascular screening
EGFR Inhibitors (Gefitinib/Erlotinib/Cetuximab)
- Acneiform rash (marker of efficacy) → topical clindamycin + oral doxycycline
- Interstitial lung disease → discontinue + high-dose steroids
- Cetuximab → Hypomagnesaemia → Mg²⁺ supplementation
Trastuzumab (HER2)
- Reversible cardiomyopathy → serial ECHO; do NOT combine with anthracyclines concurrently
Angiogenesis Inhibitors (Bevacizumab/Sunitinib/Sorafenib)
- Hypertension (class effect) → ACE inhibitor/ARB
- Bevacizumab → GI perforation + impaired wound healing → hold 4-6 weeks perioperatively
- Proteinuria → urine protein monitoring
- Sunitinib → Hypothyroidism → TFT monitoring
- Hand-Foot skin reaction → urea cream + dose reduction
Bortezomib
- Peripheral neuropathy → switch to SC route + weekly dosing
- Herpes Zoster reactivation → mandatory acyclovir prophylaxis
IMiDs (Thalidomide/Lenalidomide)
- Teratogenicity → strict REMS program; mandatory contraception
- DVT/PE → mandatory thromboprophylaxis (aspirin or LMWH)
- Thalidomide → peripheral neuropathy + sedation
- Lenalidomide → myelosuppression
HORMONAL DRUGS
| Drug | Key Toxicity | Management |
|---|---|---|
| Tamoxifen (SERM) | Endometrial cancer + DVT + Hot flushes | Annual gynae review; thromboprophylaxis; Venlafaxine |
| Fulvestrant (SERD) | Bone loss + Hot flushes | DEXA + bisphosphonates + Ca/Vit D |
| Aromatase Inhibitors | Arthralgia + Osteoporosis (most important) | DEXA + Zoledronic acid + Ca/Vit D |
| Flutamide | Hepatotoxicity (fatal) | Monthly LFTs; switch to Bicalutamide |
| GnRH Analogues | Tumour flare (initial) + Osteoporosis | Antiandrogen cover first 4 weeks; bisphosphonates |
| Rituximab (CD20) | Infusion reaction + HBV reactivation | Premedicate; screen & treat HBV prophylactically |
3 drugs needing gene screening: DPYD (5-FU) · TPMT (6-MP) · UGT1A1 (Irinotecan) 3 drugs causing secondary AML: Alkylators · Etoposide · Anthracyclines
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