Chemotherapy Toxicities - Beau Hilton
- The role of Intern/Resident on the Hematology/Oncology services is largely to work with the fellow to monitor and manage adverse effects of chemotherapy
- Concerns about specific immune-related adverse event: refer to “Toxicities associated with checkpoint inhibitor immunotherapy,” on UpToDate
- Treatment of immune checkpoint inhibitor toxicities: “Management of Immunotherapy-Related Toxicities” in the NCCN Guidelines for Supportive Care section
Neutropenia:
- Chemotherapy-associated: usually 5-18 days after treatment
- Cancer infiltrate of bone marrow
- New occult infection: especially EBV, CMV
- Patients can be safely discharged with ANC > 500
Mucositis:
- Worst in pts receiving concurrent radiation to head and neck, rectum, prostate
- Begins shortly after chemo dose, usually peaks on day 7
- High risk: bleomycin, cytarabine, anthracyclines, etoposide, 5-FU, methotrexate
- Treatment: “Salt and soda” rinses (1 tsp salt, 1 tsp baking sode in 1-quart water, swish and spit 5 times per day), viscous lidocaine, capsaicin candy, Magic Mouthwash
Immune Checkpoint Inhibitor Toxicities:
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 (ipilimumab) |
Incidence with anti‐PD1/PD‐L1 (nivolumab, pembrolizumab) |
|
Skin (pruritus, acne, TEN) |
30% |
30% |
|
Colitis |
25% |
5% |
|
Hypothyroidism |
20% |
20% |
|
Hepatitis |
10% |
1% |
|
Hypophysitis |
10% |
rare |
|
Pneumonitis |
2-5% |
2-5% |
|
Myocarditis (fatality>25%) |
<1% |
<1% |
|
Neurotoxicity (GBS, myasthenia gravis, encephalitis) |
<1% |
<1% |
Chemotherapeutic Agent Toxicities
|
Organ System |
Agent |
Side Effect |
|
Alkylating Agents |
Busulfan |
Pulmonary fibrosis or diffuse alveolar hemorrhage (8%) |
|
Cyclophosphamide |
Myopericarditis. Hemorrhagic cystitis (prevention: hydration; monitoring: daily UA, Tx: Mesna |
|
|
Ifosfamide |
Encephalopathy (tx: methylene blue) |
|
|
Antimetabolites |
5- Fluorouracil (5-FU)/ Capecitabine (metabolized to FU) |
Coronary vasospasm (ppx: CCB); palmar-plantar erythrodysesthesia |
|
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. Decrease dose only if hyperbilirubinemia. |
|
|
Methotrexate |
Hepatotoxicity, renal failure, high dose requires leucovorin |
|
|
Antitumor antibiotics |
Anthracyclines (doxorubicin, duanorubicin, idarubicin) |
HFrEF (need TTE prior). Most notable with doxorubicin. |
|
Bleomycin |
Pulmonary fibrosis (10%). Potentiated with G-CSF |
|
|
Monoclonal Antibodies |
Alemtuzumab |
Severe and prolonged cytopenias |
|
Bevacizumab |
HFrEF, HTN, hyperglycemia, hypomag, DVT, pulm hemorrhage |
|
|
Rituximab |
Hypophos, hepatotoxicity, HBV reactivation (screen all patients), peripheral neuropathy |
|
|
Platinum Agents |
Cisplatin, oxaliplatin, carboplatin |
Nephrotoxicity, worst with cisplatin. Rental tubular acidosis. Neurotoxicity- >85% oxaliplatin (parasthesias, cold sensitivity, cramps), neuropathy, ototoxicity |
|
Taxanes |
Docetaxel, paclitaxel |
Hypersensivitivy reaction. Often require premedication with steroids and H1/H2 blockers. |
|
Topoisomerase Inhibitors |
Irinotecan, topotecan, etoposide |
Irinotecan- acute diarrhea can be treated 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) |