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 is a bladder irritant and causes hemorrhagic cystitis. Treatment is by hydration and Mesna (mercaptoethanesulfonate).
Amifostine or ethyol is an antioxidant that is used to decrease nephrotoxicity caused by cisplatin and to reduce xerostomia resulting from radiotherapy to the head and neck.
Mechanism of resistance to chemotherapeutic drugs
- Genomic instability and tumor heterogeneity
- Cytokines, growth factors in the tumor microenvironment
- Cancer stem cells escape drugs by overexpression of ATP binding cassette or ABC, drug transporters like ABCB1 and ABCG2 , drug efflux pumps, inhibition of apoptosis etc.
- Drug inactivation by increased expression of the GST or glutathione S-transferase enzymes
- Multidrug resistance by increased efflux of drug by ATP dependent transporters like P-glycoprotein, MRP1 and BCRP/ABCG2
- Decreasing the absorption of drugs by decreasing the 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
- Altering 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 number of target genes like dihydrofolate reductase, oncogenes and oncoproteins
- Epigenetic changes like DNA acetylation and methylation
- Changes in micro RNA or miRNA regulating gene expression
Tumor lysis syndrome: It is a syndrome caused by the lysis of tumor cells, often after chemotherapy, leading to hyperuricemia, hyperkalemia, hyperphosphatemia and hypocalcemia. It manifests 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 is with 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.
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