Adverse effects of chemotherapeutic drugs
Common adverse effects of chemotherapeutic drugs
| Drug | Adverse effect |
| Vinca alkaloids | Peripheral neuropathy, bone marrow suppression, GI upset, alopecia |
| Taxanes | Peripheral neuropathy, edema, neutropenia, thrombocytopenia, hypersensitivity reactions; Thalidomide is teratogenic and causes limb defects like dysmelia |
| Methotrexate | Mucositis, skin and mucosal ulcers, GI toxicity, hepatotoxicity, pulmonary fibrosis; Prevent toxicity with prophylactic leucovorin/folinic acid |
| Mercaptopurine | Bone marrow suppression, cholestasis, jaundice |
| Irinotecan | Diarrhea |
| Ifosfamide | Hemorrhagic cystitis |
| Cyclophosphamide | Hemorrhagic cystitis, bone marrow suppression, alopecia, GI upset, SIADH, pulmonary and cardiac toxicity |
| 5 fluorouracil | GI upset, diarrhea, alopecia |
| Doxorubicin, daunorubicin | Cardiac toxicity, arrhythmias, cardiomyopathy, CCF; Liposomal formulations are less cardiotoxic; Dexrazoxane protects against cardiotoxicity. Dexrazoxane chelates iron, limiting the formation of free radical generating anthracycline-iron complexes, which prevents free radical mediated cardiotoxicity |
| Bleomycin | Pulmonary fibrosis, pneumonitis, hypersensitivity, hyperkeratosis, skin blisters |
| Cisplatin | Ototoxicity, neurotoxicity, peripheral neuropathy, vomiting, nephrotoxicity, myelosuppression |
| Cytarabine | Neurotoxicity, conjunctivitis, keratitis |
| Procarbazine | Neurotoxicity, peripheral neuropathy, vomiting, myelosuppression, skin reactions and disulfiram-like reaction |
| Busulfan | Pulmonary fibrosis, adrenal insufficiency, skin pigmentation |
Acrolein is a by-product of cyclophosphamide and ifosfamide. It irritates the bladder and causes hemorrhagic cystitis. Treatment is hydration and Mesna (mercaptoethanesulfonate).
Amifostine (Ethyol) is an antioxidant used to:
- Decrease nephrotoxicity caused by cisplatin
- Reduce xerostomia resulting from radiotherapy to the head and neck
Mechanism of resistance to chemotherapeutic drugs
- Genomic instability and tumor heterogeneity
- Cytokines and growth factors in the tumor microenvironment
- Cancer stem cells escape drugs by overexpression of ATP binding cassette (ABC) drug transporters (e.g., ABCB1 and ABCG2), drug efflux pumps, inhibition of apoptosis, etc.
- Drug inactivation by increased expression of GST (glutathione S-transferase) enzymes
- Multidrug resistance due to increased efflux of drug by ATP dependent transporters like P-glycoprotein, MRP1 and BCRP/ABCG2
- Decreased absorption of drugs due to a reduced number of drug transporters
- Inhibition of apoptosis by upregulation of anti-apoptotic genes (Bcl2, AKT) and down regulation of pro-apoptotic genes like Bax, Bclxl
- Mutations in p53 gene
- Altered drug metabolism by decreasing activation of prodrugs to drugs and increasing inactivation of drugs
- Modification of drug targets like topoisomerases
- Enhanced DNA repair
- Gene amplification increases the number of target genes like dihydrofolate reductase, oncogenes and oncoproteins
- Epigenetic changes like DNA acetylation and methylation
- Changes in micro RNA (miRNA) regulating gene expression
Tumor lysis syndrome: Tumor lysis syndrome is caused by rapid lysis of tumor cells (often after chemotherapy), leading to hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia. It can manifest as renal failure, arrhythmias, seizures, tetany, carpopedal spasm, muscle twitchings, and multiorgan failure. SIRS and cytokine release contribute to multiorgan failure. Uric acid and calcium phosphate stones may precipitate in the kidney. It is more often seen in leukemias and lymphomas. Prevention and treatment include good hydration, diuretics like furosemide (if needed) to increase urine output, allopurinol and rasburicase (more effective) to decrease uric acid formation, treatment of hyperkalemia, and dialysis if necessary.