Chemotherapeutic agents are used to control cancer cell proliferation, but they often come with toxicities to the host as well. It is important to monitor patients closely for the development of toxicities during therapy. Some of the potential toxicities of common chemotherapeutics are outlined below in our Chemotherapy Toxicity Table.
Myelosuppression is a common adverse effect that can occur with most chemotherapeutic agents, with the exception being asparaginase, bleomycin, vincristine, and many monoclonal antibodies or tyrosine kinase inhibitors. Myelosuppression can be monitored by getting a CBC with differential, checking temperature, and looking for symptoms such as bleeding, fatigue, or shortness of breath. Management of myelosuppression includes colony-stimulating factors for neutropenia, red blood cell transfusions for anemia, and platelet transfusions for thrombocytopenia.
Nausea and vomiting is most common with cisplatin, cyclophosphamide, and ifosfamide. It can be treated with a variety of agents including neurokinin-1 receptor antagonists, serotonin-3 receptor antagonists, dexamethasone, prochlorperazine, and metoclopramide. Diarrhea is also common with irinotecan, capecitabine, fluorouracil, and methotrexate. Hydration and antimotility medications like loperamide can be used. Atropine can be effective for early diarrhea due to irinotecan. Conversely, constipation can occur commonly with vincristine and can be treated with polyethylene glycol.
Cardiotoxicity can occur with fluorouracil, anthracyclines (i.e. doxorubicin), and HER2 inhibitors. Due to the cardiomyopathy that can occur, doxorubicin has a maximum lifetime cumulative dose of 450-550 mg/m^2. Pulmonary toxicity can occur with bleomycin, resulting in bleomycin having a lifetime maximum cumulative dose of 400 units.
Nephrotoxicity can occur with cisplatin and high doses of methotrexate. It is important to monitor kidney function including BUN, urinalysis, and SCr. For cisplatin, amifostine can be given as prophylaxis to reduce the chance of nephrotoxicity. Adequate hydration is important. Additionally, hemorrhagic cystitis can occur with ifosfamide as well as high doses of cyclophosphamide. Due to this risk, Mesna must always be given with ifosfamide, and may also be given with cyclophosphamide if indicated.
Neuropathy is a potential toxicity that can occur with vincristine, cisplatin, oxaliplatin, and paclitaxel. It is important to monitor patients for signs of neuropathy such as numbness or tingling in the extremities. Due to neuropathy risk, vincristine should be limited to 2mg weekly or less. Oxaliplatin can cause neuropathy that is triggered by cold temperatures.
Finally, tamoxifen can bring an increased thromboembolic risk. Monitor patients for signs of clots such as DVT, PE, or stroke. If risk factors are present, patients may be indicated for thromboprophylaxis. While we recognize that the table below is limited, it highlights some really important things that may show up on board exams 🙂 Here’s our chemotherapy toxicity table.
|cyclophosphamide||None||Myelosuppression, hemorrhagic cystitis (high dose), N&V||Give with mesna if high dose (>1g/m^2). Monitor: CBC, BUN, SCr, hemorrhagic cystitis, renal toxicity, pulmonary toxicity, cardiac toxicity, hepatic toxicity|
|doxorubicin||Cardiomyopathy, extravasation, secondary malignancy, myelosuppression||Cardiomyopathy, myelosuppression||Vesicant, MUGA/ECHO before starting therapy. Monitor CBC, LFT, Ca, K, SCr, cardiac function, and hydration status.|
|fluorouracil||None||Mucositis, diarrhea, cardiomyopathy||Monitor CBC, LFT, INR, CNS toxicity, stomatitis, diarrhea, hyperammonemic encephalopathy, hand-foot syndrome|
|vincristine||Experienced provider, extravasation, IV use only||Peripheral neuropathies, constipation||Vesicant, Intrathecal dosing is fatal.Monitor: electrolytes, hepatic function, CBC, hepatic sinusoidal obstruction, constipation, neurologic exam, peripheral neuropathy|
|capecitabine||Interaction with warfarin||Hand-foot syndrome, dermatitis, paresthesias, diarrhea||Interacts with warfarin and phenytoin. Monitor: CBC, hepatic function, renal function, INR, diarrhea, dehydration, hand-foot syndrome, Stevens-Johnsons, toxic epidermal necrolysis, stomatitis, cardiotoxicity|
|methotrexate||Hypersensitivity, pregnancy, bone marrow suppression, renal impairment, hepatotoxicity, pneumonitis, GI toxicity, secondary malignancy, tumor lysis syndrome, dermatologic toxicity, opportunistic infections, radiotherapy, experienced physician||Myelosuppression, nephrotoxicity, mucositis, diarrhea, pneumonitis||Monitor: CBC, BUN, LFT, methotrexate levels, SCr, urine pH, fluid/electrolytes, pulmonary function, renal function, hepatic function|
|irinotecan||Diarrhea, bone marrow suppression||Diarrhea, myelosuppression||Give with atropine for early diarrhea, and loperamide for late diarrhea. Monitor: CBC, electrolytes, bowel movements, hydration, pulmonary toxicity|
|paclitaxel||Experienced physician, hypersensitivity, bone marrow suppression||Myelosuppression, alopecia, cardiac toxicity, peripheral neuropathy, myalgia||Requires filter and non PVC tubing.Premedicate with diphenhydramine, H2 agonist, dexamethasone.Monitor: CBC, kidney function, hypersensitivity, infusion site|
|Ifosfamide||Bone marrow suppression, CNS toxicity, hemorrhagic cystitis, nephrotoxicity||Nephrotoxicity, hemorrhagic cystitis, N&V||Need to give with Mesna to bind toxic metabolite. Monitor: CBC, urine output, urinalysis, liver function, renal function, neurotoxicity, pulmonary toxicity, hemorrhagic cystitis|
|cisplatin||Myelosuppression, N&V, nephrotoxicity, peripheral neuropathy||Nephrotoxicity, N&V, neurotoxicity, ototoxicity, peripheral neuropathy||Vigorous pre and post-hydration to preserve kidney function. Monitor: SCr, electrolytes, neurological function, hypersensitivity, neuropathy, ocular toxicity, secondary malignancies|
|carboplatin||Experienced physician, bone marrow suppression, vomiting, hypersensitivity||Alopecia, myelosuppression||Monitor: CBC, LFTs, SCr, electrolytes, hypersensitivity|
|oxaliplatin||hypersensitivity/anaphylaxis||Peripheral neuropathy, myelosuppression, diarrhea||CBC, SCr, LFTs, electrolytes, INR, ECG, neurologic function, hypersensitivity, pulmonary toxicity, posterior reversible encephalopathy syndrome, neuropathy, GI toxicity, bleeding|
|daunorubicin||Experienced physician, extravasation, bone marrow suppression, cardiomyopathy, hepatic impairment, renal impairment||Cardiotoxicity, myelosuppression||Monitor: CBC, LFTs, ECG, renal function, LVEF (ECHO or MUGA)|
|bleomycin||Experienced physician, pulmonary toxicity, idiosyncratic reaction||Pulmonary fibrosis, hepatotoxicity||Monitor pulmonary function, renal function, liver function|
|tamoxifen||Uterine malignancies and thromboembobleolic events||Thromboembolic risk||Consider thromboprophylaxis based on risk. Monitor CBC, INR, LFT, vaginal bleeding. Breast and pelvic exam. CYP2D6 inhibitors may impair effectiveness.|
|cytarabine||Experienced physician, drug toxicity (bone marrow suppression, N&V, diarrhea, hepatic dysfunction)||Myalgia, myelosuppression, N&V, diarrhea, oral ulceration, hepatic dysfunction||Monitor: LFT, CBC, BUN, signs of bleeding, infection, neutropenic fever, tumor lysis syndrome|
The article was written by Melody Grafton in collaboration with Eric Christianson, PharmD, BCGP, BCPS
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