Chemotherapy Toxicity

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 antiPD1/PDL1 (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)