Preparatory Mindset
Anticancer drugs are classified by cell cycle specificity (CCSA vs CCNSA) and mechanism. Key associations: cyclophosphamide → hemorrhagic cystitis (prevent with mesna), doxorubicin → cardiotoxicity (cumulative dose limit), bleomycin → pulmonary fibrosis, vincristine → neuropathy. Most common dose-limiting toxicity: bone marrow suppression.
Core Concepts
Ch10: Anti-Cancer
Drug Classification by Cell Cycle Specificity
| Category | Cell Cycle | Drugs |
|----------|-----------|-------|
| Cell Cycle Non-Specific (CCNSA) | All phases (including G0) | Alkylating agents (Cyclophosphamide), Antitumor antibiotics (Doxorubicin), Platinum drugs |
| Cell Cycle Specific (CCSA) | Specific phase | S-phase: Antimetabolites (MTX, 5-FU, Cytarabine, 6-MP); M-phase: Vinca alkaloids (Vincristine), Taxanes (Paclitaxel) |
Key Drug Table by Class
1. Antimetabolites (S-phase Specific)
| Drug | MOA | Clinical Use | Key Toxicity |
|------|-----|-------------|-------------|
| Methotrexate (MTX) | Inhibits DHFR → ↓ THF → ↓ DNA synthesis | ALL, solid tumors, rheumatoid arthritis | Myelosuppression; leucovorin rescue (calcium folinate) |
| 5-Fluorouracil (5-FU) | Inhibits thymidylate synthase → ↓ dTMP | Colorectal, breast, GI cancers | GI mucositis; hand-foot syndrome |
| Cytarabine (Ara-C) | Inhibits DNA polymerase | AML | Myelosuppression; cerebellar toxicity |
| 6-Mercaptopurine (6-MP) | Purine analogue | ALL | Myelosuppression; metabolized by XO (interaction with allopurinol) |
2. Alkylating Agents (CCNSA)
| Drug | MOA | Key Toxicity | Notes |
|------|-----|-------------|-------|
| Cyclophosphamide (CTX) | Alkylates DNA → cross-links | Hemorrhagic cystitis (acrolein); myelosuppression | Active metabolite: Phosphoramide mustard; prevent with mesna + hydration |
| Nitrogen Mustard | Same | Myelosuppression, vesicant | First alkylating agent |
| Chlorambucil | Same | Myelosuppression | CLL |
3. Platinum Drugs
| Drug | Key Toxicity | Notes |
|------|-------------|-------|
| Cisplatin | Nephrotoxicity + Ototoxicity (dose-limiting) | Pre-hydration + mannitol; also causes severe nausea |
| Carboplatin | Myelosuppression (thrombocytopenia) | Better tolerated, less nephro/oto-toxicity |
| Oxaliplatin | Peripheral neuropathy, cold sensitivity | Colorectal cancer |
4. Antitumor Antibiotics
| Drug | Key Toxicity | Notes |
|------|-------------|-------|
| Doxorubicin (Adriamycin) | Cardiotoxicity (cumulative dose-limiting) | Free radical damage to myocytes; limit lifetime dose |
| Bleomycin | Pulmonary fibrosis (dose-limiting) | Minimal myelosuppression (unique!) |
| Daunorubicin | Cardiotoxicity | AML induction |
| Actinomycin D | Myelosuppression | Pediatric tumors |
5. Plant Alkaloids
| Drug | MOA | Key Toxicity | Notes |
|------|-----|-------------|-------|
| Vincristine (VCR) | Inhibits microtubule polymerization (M-phase) | Peripheral neuropathy (dose-limiting) | Minimal myelosuppression (unique!) |
| Vinblastine | Same | Myelosuppression | Less neurotoxicity than VCR |
| Paclitaxel (Taxol) | Promotes microtubule polymerization → stabilizes | Peripheral neuropathy, hypersensitivity | Pre-medicate with steroids + antihistamines |
6. Topoisomerase Inhibitors
| Drug | MOA | Key Toxicity |
|------|-----|-------------|
| Etoposide | Topoisomerase II inhibitor | Myelosuppression |
| Irinotecan | Topoisomerase I inhibitor | Delayed severe diarrhea |
7. Non-Cytotoxic / Targeted Therapy
| Class | Example | Target | Use |
|-------|---------|--------|-----|
| Hormonal | Tamoxifen (SERM), Letrozole (aromatase inhibitor) | ER+ breast cancer | Breast cancer |
| Tyrosine Kinase Inhibitor | Imatinib | BCR-ABL | CML, GIST |
| Monoclonal Antibody | Trastuzumab (Herceptin) | HER2+ | Breast cancer |
| Differentiating Agent | ATRA | PML-RARα | APL (acute promyelocytic leukemia) |
Key Toxicity Summary
| Drug | Dose-limiting Toxicity |
|------|----------------------|
| Doxorubicin | Cardiotoxicity (cumulative) |
| Bleomycin | Pulmonary fibrosis |
| Cisplatin | Nephrotoxicity + Ototoxicity |
| Carboplatin | Myelosuppression |
| Vincristine | Peripheral neuropathy |
| Cyclophosphamide | Hemorrhagic cystitis |
| Paclitaxel | Peripheral neuropathy |
| Irinotecan | Delayed diarrhea |
| Methotrexate | Myelosuppression, mucositis |
High-Yield Points
- Bone marrow suppression: MOST COMMON dose-limiting toxicity
- Cyclophosphamide → hemorrhagic cystitis → prevent with MESNA + hydration
- Doxorubicin → cardiotoxicity (cumulative, limit ~450-550 mg/m²) → prevent with dexrazoxane
- Bleomycin → pulmonary fibrosis → limit to 400 units cumulative
- Vincristine → peripheral neuropathy — MINIMAL myelosuppression
- Cisplatin → nephrotoxicity + ototoxicity
- High-dose MTX → leucovorin rescue (provides reduced folate, bypasses DHFR)
- Tamoxifen: SERM — antagonist in breast, partial agonist in bone/uterus (↑ endometrial cancer risk)
Topic Summary
Cytotoxic drugs cause bone marrow suppression as the most common dose-limiting toxicity. Characteristic toxicities: cyclophosphamide → hemorrhagic cystitis (mesna), doxorubicin → cardiotoxicity (dexrazoxane), bleomycin → pulmonary fibrosis, vincristine → neuropathy. Hormonal agents (tamoxifen) do NOT cause myelosuppression.