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 pts), 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) |