Therapy Toxicities¶
Rahul Shah
Immune Checkpoint Inhibitor Toxicities¶
- Immune checkpoint inhibitors augment the endogenous immune response against tumors, which may lead to autoimmune-like toxicities, known as immune-related adverse events (irAEs)
- Treatment: low-dose glucocorticoids (prednisone, 0.5 mg/kg) for mild adverse events, high dose glucocorticoids (prednisone, 1-2 mg/kg) for severe adverse events
| Adverse Event Type | Incidence with anti-CTLA-4 (e.g. ipilimumab) |
Incidence with anti‐PD1/PD‐L1 (e.g. nivolumab, pembrolizumab) |
|---|---|---|
| Skin (rash, pruritus, TEN) | 30% | 30% |
| Colitis | 25% | 5% |
| Hypothyroidism | 20% | 20% |
| Hepatitis | 10% | 1% |
| Hypophysitis | 10% | rare |
| Pneumonitis | 2-5% | 2-5% |
| Myocarditis | <1% | <1% |
| Neurotoxicity (GBS, myasthenia gravis, encephalitis) | <1% | <1% |
Cytotoxic Agent Toxicities¶
| Class | Agent | Side Effect |
|---|---|---|
| Alkylating Agents | Busulfan | Pulmonary fibrosis or diffuse alveolar hemorrhage |
| Cyclophosphamide | Myopericarditis, hemorrhagic cystitis (prevention: hydration; monitoring: daily UA, tx: mesna) | |
| Ifosfamide | Encephalopathy (tx: methylene blue), nephrotoxicity, hemorrhagic cystitis | |
| Antimetabolites | 5- Fluorouracil (5-FU)/ Capecitabine (metabolized to FU) | Myelosuppression, coronary vasospasm, palmar-plantar erythrodysesthesia, mucositis |
| Cladribine, pentostatin | Dose reduced for CrCl | |
| Cytarabine (Ara-C) | Irreversible cerebellar ataxia (if high dose, neuro checks required), conjunctivitis (prevent with prophylactic steroid eye drops) | |
| Gemcitabine | Transient transaminitis, peripheral edema, rash, rarely: pulmonary toxicity, hemolytic uremic syndrome, capillary leak syndrome | |
| Methotrexate | Stomatitis, hepatotoxicity, renal failure, high dose requires leucovorin | |
| Antitumor antibiotics | Anthracyclines (doxorubicin, daunorubicin, idarubicin) | HFrEF (need TTE prior). Most notable with doxorubicin. |
| Bleomycin | Pulmonary fibrosis. Potentiated with G-CSF | |
| Monoclonal Antibodies | Alemtuzumab | Severe and prolonged cytopenias |
| Bevacizumab | HFrEF, HTN, hyperglycemia, hypomag, DVT, pulm hemorrhage, GI bleeding/fistulas/perforation, wound healing complications | |
| Rituximab | Hypophos, hepatotoxicity, HBV reactivation (screen all patients), peripheral neuropathy; transfusion reaction during 1st time infusion | |
| Platinum Agents | Cisplatin, oxaliplatin, carboplatin | Nephrotoxicity, worst with cisplatin. Rental tubular acidosis. Neurotoxicity (parasthesias, cold sensitivity, cramps, peripheral neuropathy), ototoxicity (high frequency hearing loss), constipation, hypomag |
| Taxanes | Docetaxel, paclitaxel | Hypersensitivity reaction (often require premedication with steroids and H1/H2 blockers); peripheral neuropathy |
| Topoisomerase Inhibitors | Irinotecan, topotecan, etoposide | Irinotecan- acute diarrhea can be treated with atropine; delayed with atropine |
| Tyrosine Kinase Inhibitors | Imatinib, Dasatinib, Nilotinib, Bosutinib | QTc prolongation, pulmonary effusion, hepatotoxicity |
| Vinca alkaloid | Vincristine | Peripheral neuropathy and ototoxicity (vestibular system lost first) |
Last update:
2022-06-25 02:05:01