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