Complications of cancer therapy

Cancer therapy (including chemotherapy, radiation therapy, surgery, cancer immunotherapy, and other targeted therapies) often results in complications affecting various body systems. The most common complications include nausea and vomiting, mucositis, alopecia, and myelosuppression. Certain complications (e.g., increased cardiovascular risk, secondary osteoporosis, and pulmonary fibrosis) persist after treatment is completed. Some types of cancer therapy also increase the risk of second cancer. Complications require careful monitoring and management to ensure patient safety and quality of life. Management of immune checkpoint inhibitor complications may include glucocorticoids and treatment discontinuation.

Preparation for cancer therapy, including prevention strategies for complications, is described in “Principles of cancer care.”

Complications of radiation therapy are described in further detail in “Local radiation injuries.”

Complications listed by agent can be found in “Chemotherapeutic agents” and “Immunosuppressants.”

See “Oncologic emergencies” and “Neutropenic fever” for details on the diagnosis and management of life-threatening complications such as neutropenic fever and tumor lysis syndrome.

Approach to management ^[1][2]

• In most cases, management should be guided by oncology and/or other relevant specialties (e.g., cardiology, nephrology) depending on the complication type.
• Management of acute complications depends on the type and severity of cancer therapy-induced complications and may include:
  • Monitoring, e.g., laboratory studies for myelosuppression
  • Supportive care, e.g., antiemetics for nausea
  • Adjustments in cancer therapy, e.g., discontinuation for higher-grade toxicities
• Start immediate management for any severe or life-threatening complications, e.g., neutropenic fever, or tumor lysis syndrome.
• Consider screening for long-term complications of cancer therapy based on the type and location of cancer therapy.
• See also “Cancer-related complications,” “Paraneoplastic syndromes,” and “Oncologic emergencies.”

Differentiating between complications caused by cancer and those caused by treatment is often challenging.

Overview of complications

Severity of cancer therapy-induced complications ^[10]

Severity of each type of complication (e.g., gastrointestinal, hematologic) can be graded using the Common Terminology Criteria for Adverse Events (CTCAE) criteria, and the need for management should be evaluated accordingly.

• Grade 1 (asymptomatic or mild): Closely monitor the patient; no intervention is indicated.
• Grade 2 (moderate; symptoms limit instrumental activities of daily living): Minimal or noninvasive intervention is indicated.
• Grade 3 (severe; symptoms limit basic activities of daily living): Hospitalization is indicated.
• Grade 4 (immediately life-threatening): Urgent intervention is indicated.

Management of complications of immune checkpoint inhibitors ^[11]

Immune checkpoint inhibitors can lead to autoimmune-like adverse effects. ^[11]

• Management should be guided by hematology-oncology.
• Obtain laboratory and imaging studies based on suspected organ toxicity.
• Grade 1 toxicity: Continue therapy with close monitoring in most cases.
• Grade 2 toxicity
  • Consider temporary discontinuation until symptoms and laboratory values reach ≤ grade 1.
  • Consider glucocorticoids, e.g., prednisone. ^[11]
• Grade 3 toxicity
  • Temporary discontinuation until symptoms and laboratory values reach ≤ grade 1
  • Start high-dose glucocorticoids, e.g., prednisone ; additional immunosuppression may be considered if symptoms do not improve.
• Grade 4 toxicity
  • Permanent discontinuation for most patients
  • Start high-dose glucocorticoids; administer additional immunosuppression as directed by a subspecialist.
• See “Tips and Links” for details on management of specific organ toxicities.

In patients with severe organ toxicity, weigh the risks and benefits of rechallenge vs. permanent discontinuation in consultation with a specialist.

Cancer therapy-induced nausea and vomiting (CINV) ^[12][13]

Definition ^[13][14]

• Any nausea and vomiting associated with chemotherapy
• Further subcategorized as:
  • Acute CINV: onset within 24 hours after chemotherapy
  • Delayed CINV: onset between 24 and 120 hours after chemotherapy
  • Anticipatory CINV: onset prior to chemotherapy as a conditioned response following nausea or vomiting with previous chemotherapy
  • Breakthrough CINV: occurs despite the use of standard antiemetic prophylaxis
  • Refractory CINV: occurs in patients with a history of CINV unresponsive to prophylactic and rescue antiemetic therapy during previous chemotherapy

Associated cancer therapies ^[12]

• Chemotherapy
  • Alkylating agents, e.g., cisplatin, high-dose cyclophosphamide, carmustine
  • Anthracyclines, e.g., doxorubicin, daunorubicin
  • Antimetabolites, e.g., high-dose cytarabine
  • Topoisomerase inhibitors, e.g., irinotecan
• Targeted therapy: e.g., alemtuzumab
• Radiation therapy: See also “Radiation-induced gastrointestinal injury.”

Epidemiology

• 30–60% of patients who receive chemotherapy develop CINV. ^[15]
• Risk factors include female sex, younger age, anxiety, and a history of motion or morning sickness. ^[16]

Management ^[12][13][14]

• Base the antiemetic regimen on patient characteristics and the emetogenicity of the chemotherapeutic agents.
• Initial regimen
  • Start CINV prophylaxis on the first day of chemotherapy and continue for up to 4 days depending on the regimen.
  • Commonly used agents: dexamethasone, 5-HT3 receptor antagonists, NK1 receptor antagonists
• Breakthrough CINV or refractory CINV: Add antiemetics of a different class (e.g., olanzapine, benzodiazepines, dopamine receptor antagonists).
• Delayed CINV: dexamethasone and NK1 receptor antagonist (e.g., aprepitant)
• Anticipatory CINV: Optimize prophylaxis and consider benzodiazepines and/or behavioral therapy.
• Patients with active nausea/vomiting may require management of dehydration, including electrolyte correction.

Cancer therapy-induced diarrhea ^[17][18][19]

Definition ^[19]

• ≥ 3 loose or watery stools per day in patients receiving chemotherapy
• Subdivided into:
  • Uncomplicated diarrhea
  • Complicated diarrhea

Associated cancer therapies ^[17][19]

• Chemotherapy
  • Antimetabolites: e.g., 5-fluorouracil, capecitabine
  • Topoisomerase inhibitors: e.g., irinotecan
  • Taxanes: e.g., docetaxel
  • Anthracyclines: e.g., doxorubicin
  • Platinum-based agents: e.g., cisplatin
• Cancer immunotherapy: e.g., immune checkpoint inhibitors ^[11]
• Radiation therapy: See also “Radiation-induced gastrointestinal injury.”

Epidemiology

• Up to 80% of patients receiving chemotherapy ^[18][20]
• Irinotecan and 5-fluorouracil are the chemotherapeutic agents most frequently associated with diarrhea. ^[17][19]

Management of uncomplicated diarrhea ^[17][19]

• Initiate oral rehydration therapy.
• Recommend dietary interventions.
• Take precautions against perianal skin irritation.
• Consider loperamide. ^[19]
• Advise patients to seek immediate medical attention if symptoms of complicated diarrhea develop.
• Reassess after 12–24 hours.
  • Improvement in symptoms: Continue loperamide until there is no diarrhea for > 12 hours, then slowly reintroduce a normal diet.
  • No improvement or worsening of symptoms: Manage as complicated diarrhea.

Management of complicated diarrhea ^[17][19]

• Request diagnostic studies to assess for complications and rule out other causes of diarrhea.
  • Routine laboratory studies include CBC, BMP, liver chemistries, CRP, stool cultures, and C. difficile toxin test.
  • Consider blood cultures and abdominal imaging based on clinical evaluation.
• Admit for inpatient management and consider gastroenterology consult.
  • Administer initial fluids for dehydration and hypovolemia.
  • Start antidiarrheal medications.
    • First-line: loperamide ^[19]
    • Persistent diarrhea: Consider octreotide. ^[19]
  • Consider additional pharmacotherapy (e.g., antibiotics, oral budesonide) as needed. ^[19]

Do not assume a diagnosis of chemotherapy-induced diarrhea before completing a thorough assessment. Differential diagnoses include life-threatening infections, e.g., C. difficile infection and neutropenic enterocolitis. ^[19]

Cancer therapy-induced constipation ^[21][22]

• Definition: See Rome IV diagnostic criteria for primary constipation in adults.
• Associated cancer therapies
  • Chemotherapy
    • Alkylating agents: e.g., cisplatin, vincristine, vindesine, vinorelbine
    • Immune-modulating medication: e.g., thalidomide
  • Cancer immunotherapy: e.g., immune checkpoint inhibitors ^[11]
  • Radiation therapy: See also “Radiation-induced gastrointestinal injury.”
• Management: See “Cancer-related constipation” for details on management.

Differentiating between cancer-related and cancer therapy-induced constipation is often difficult, but management is identical.

Mucositis ^[23][24][25]

• Presence of inflammatory or ulcerative lesions in the mouth or GI tract following cancer therapy
• Symptoms include oral pain, dysphagia, and diarrhea.

Associated cancer therapies ^[23][26]

• Chemotherapy
  • Antimetabolites: e.g., 5-fluorouracil, methotrexate
  • Etoposide
  • Melphalan
• Targeted therapy
  • Bevacizumab
  • Trastuzumab
  • Tyrosine kinase inhibitors: e.g., lapatinib
  • mTOR inhibitors: e.g., everolimus
• Radiation therapy: e.g., radiation for head and neck cancer, myeloablative total body irradiation

Epidemiology ^[23][25]

• 20–40% of patients receiving chemotherapy
• 60–85% of patients undergoing hemopoietic stem cell transplantation (HSCT)
• Almost all patients receiving head and neck radiation ^[24]

Prevention of mucositis ^[23][24]

• Educate patients on good oral hygiene.
  • Use a soft toothbrush and brush twice daily.
  • Rinse the mouth 4–6 times a day with alcohol-free mouthwash.
  • Frequently inspect the oral mucosa.
• Advise:
  • Regular lubrication of the lips with vaseline or paraffin
  • Ample fluid intake
  • Avoidance of alcohol, smoking, and spicy, acidic, or sharply edged food
• Refer for dental evaluation and treatment (e.g., repair or replace any poorly fitting prosthesis) prior to and during cancer therapy.
• Depending on the treatment regimen, consider the following in consultation with a specialist:
  • Oral mucositis prophylaxis: oral cryotherapy, low-level laser therapy, benzydamine mouthwash, recombinant human keratinocyte growth factor-1
  • Gastrointestinal mucositis prophylaxis: probiotics, sulfasalazine, amifostine

Because of the high risk of mucositis, prophylaxis is recommended for patients receiving fluorouracil, high-dose regimens used for conditioning prior to HSCT, and radiotherapy. ^[23][24]

Management ^[23][24][25]

• General measures
  • Ensure nutritional support and hydration.
  • Optimize systemic pain management (consider patient-controlled analgesia).
• Oral mucositis
  • Start topical interventions, e.g., 2% viscous lidocaine, 0.5% doxepin, or 0.2% morphine mouthwash.
  • Consider, depending on treatment regimen, gabapentin, topical or systemic steroids, or low-level laser therapy. ^[23]
• Gastrointestinal mucositis
  • Consider hyperbaric oxygen therapy and sucralfate enemas depending on the specific regimen.
  • See “Radiation proctitis” for further information.

Provide adequate pain management to patients with mucositis. Consider initiating opioid analgesia early.

Cancer therapy-induced alopecia ^[27][28]

• A form of temporary alopecia in patients receiving cancer therapy
• Hair regrowth typically occurs 2–6 months after stopping chemotherapy; in rare cases, hair loss is permanent. ^[27]
• Occurs in ∼ 65% of patients receiving chemotherapy and frequently causes considerable psychological distress ^[4][27][28]

Associated cancer therapies ^[4][27]

• Chemotherapy
  • Anthracyclines: e.g., doxorubicin, daunorubicin
  • Taxanes: e.g., paclitaxel, docetaxel
  • Alkylating agents: e.g., cyclophosphamide
  • Topoisomerase inhibitors: e.g., irinotecan, etoposide
• Cancer immunotherapy: e.g., immune checkpoint inhibitors (causes immune-related alopecia, i.e., alopecia areata)
• Radiation therapy: e.g., radiation for brain tumors or head and neck cancer (causes anagen effluvium)

Prevention of cancer therapy-induced alopecia

• Patient education ^[28]
  • Wash hair only when necessary.
  • Use a soft brush and satin pillowcase.
  • Avoid damage to the hair, e.g., bleaching, coloring, use of curling irons or hot rollers.
• Use of scalp-cooling devices during chemotherapy ^[29]

Scalp cooling is contraindicated in patients with hematologic malignancies due to the risk of reduced chemotherapy delivery to malignant cells in the scalp circulation. ^[30]

Management

• Supportive measures
  • Use of camouflage techniques, e.g., change of hairstyle, wigs, or headwraps ^[27]
  • Refer for psychological support if emotionally distressed. ^[27]
• Topical treatments may help promote hair regrowth after chemotherapy, e.g.:
  • Bimatoprost 0.03% solution applied to the eyelid margin for eyelash alopecia ^[31]
  • Minoxidil for scalp alopecia ^[29]

Cancer therapy-induced xerosis and pruritus ^[3][4]

• Associated cancer therapies
  • Targeted therapy
    • EGFR inhibitors
    • BCR-ABL inhibitors
    • mTOR inhibitors
  • Cancer immunotherapy: immune checkpoint inhibitors
• Epidemiology: incidence of almost 100% in patients receiving long-term targeted therapy ^[3]
• Clinical features: Presentation ranges from normal-appearing skin to frank desquamation.
• Management ^[3]
  • Skin lotions with 5–10% urea
  • Oral antihistamines, e.g., cetirizine
  • Topical steroids

Hand-foot syndrome ^[4]

• Associated cancer therapies
  • Antimetabolites: e.g., 5-fluorouracil, capecitabine, tegafur
  • Anthracyclines: e.g., doxorubicin
  • Antimetabolites: e.g., cytarabine
• Clinical features
  • Painful erythematous lesions on the palms and/or soles of the feet
  • May also involve vesicles and bullae that desquamate
• Management ^[3]
  • Avoidance of physical stress to the affected areas
  • Cooling of hands and feet (e.g., chilled gloves)
  • Skin lotions with 5–10% urea
  • Topical steroids
  • Discontinuation of chemotherapy in patients with high-grade lesions

Extravasation of chemotherapeutic agents ^[32][33]

• Epidemiology: reported in up to 6% of patients with cancer ^[33]
• Clinical features
  • Pain, pressure, and swelling at the IV site
  • Leakage of infusion fluid
  • Alterations to IV flow
• Management
  • For general treatment and prevention, see “Extravasation injuries.”
  • Tailor the management to the chemotherapeutic agent (e.g., use of a reversal agent), under specialist guidance (e.g., oncology, plastic surgery).

Extravasation of vesicants may lead to severe complications such as soft tissue necrosis or compartment syndrome. ^[33]

General principles of cancer therapy-induced myelosuppression ^[34]

• One of the most common side effects, particularly during induction chemotherapy ^[35]
• Actively monitor for myelosuppression in all patients receiving chemotherapy or systemic radiotherapy.
  • Perform regular CBCs, typically before each treatment cycle.
  • Advise patients to seek immediate attention if they develop a fever, symptoms of anemia, or symptoms of thrombocytopenia.
• If myelosuppression is identified, start early management, which can include:
  • Adjustments in the chemotherapy regimen
  • Transfusion of blood products (check for special transfusion requirements)
  • Agents that mobilize or stimulate cell production, e.g., granulocyte colony-stimulating factor

Patients with cancer often require blood products that have been irradiated, are leukoreduced, and/or come from CMV-seronegative donors. ^[36]

Management of cancer therapy-induced anemia ^[37][38]

• Screen for and treat vitamin B₁₂, folate, and iron deficiency anemia. ^[38]
• Transfusion of packed RBCs: indicated for severe anemia or certain patients with moderate anemia ^[39]
• Erythropoiesis-stimulating agents (ESA): Consider in selected patients after anemia workup. ^[37][38]

Management of cancer therapy-induced thrombocytopenia ^[40][41][42]

• Initial management
  • Initiate emergency management of thrombocytopenia for patients with significant active bleeding.
  • Consider platelet transfusions; indications for platelet transfusion are similar to patients without cancer.^[40]
  • In consultation with oncology, consider delaying or reducing the dose of scheduled chemotherapy. ^[42]
• Discuss additional measures, such as pharmacological prophylaxis or treatment, with hematology.
  • Recombinant IL-11 (oprelvekin) is approved for treating chemotherapy-induced thrombocytopenia but has severe adverse effects. ^[43]
  • Antifibrinolytics and thrombopoietin-receptor agonists (TPO-RAs) have been used, but efficacy and indications for use are still being studied. ^[43][44][45]

Management of cancer therapy-induced neutropenia ^[46][47][48]

• Advise patients on infection prevention in cancer therapy-induced neutropenia. ^[49]
  • Wash hands regularly.
  • Avoid eating unwashed fruits or vegetables and undercooked meat, seafood, or eggs.
  • Keep catheter sites clean and dry.
  • Remain up-to-date on recommended vaccinations.
  • Avoid contact with unwell individuals.
  • Follow local health authority guidance on mask-wearing and social distancing to reduce the risk of COVID-19 infection.
• Consider granulocyte colony-stimulating factor (e.g., filgrastim, pegfilgrastim) or granulocyte-macrophage colony-stimulating factor (e.g., sargramostim) for: ^[46][48]
  • Patients with febrile neutropenia who are at high risk for complications
  • Prophylaxis in certain patients receiving cancer therapy
• Antimicrobial prophylaxis (e.g., trimethoprim/sulfamethoxazole against Pneumocystis jirovecii pneumonia, fluconazole against invasive candidiasis) is limited to high-risk patients under specialist guidance. ^[47]
• Monitor frequently for signs of infection and maintain a low threshold for starting aggressive antimicrobial treatment (see “Neutropenic fever”).

Cancer therapy-induced cardiomyopathy ^[6][50]

Associated cancer therapies ^[50]

• Chemotherapy
  • Anthracyclines: e.g., doxorubicin
  • Alkylating agents: e.g., cyclophosphamide
  • Antimetabolites: e.g., 5-fluorouracil
• Targeted therapy
  • Proteasome inhibitors: e.g., bortezomib
  • mTOR inhibitors: e.g., everolimus
  • Monoclonal antibodies: e.g., trastuzumab
  • Protein kinase inhibitors: e.g., VEGFR tyrosine kinase inhibitors
• Cancer immunotherapy: immune checkpoint inhibitors
• Radiation therapy: e.g., radiation for breast cancer

Management ^[50]

Management is specialist-guided and includes:

• Management of heart failure, e.g., beta blockers, ACE inhibitors
• Treatment adjustments to reduce cardiotoxicity
• Immunosuppression for immune checkpoint inhibitor-induced cardiomyopathy

Arrhythmias ^[5][50]

Associated cancer therapies ^[50]

• Chemotherapy
  • Alkylating agents: e.g., cyclophosphamide
  • Platinum-based agents: e.g., cisplatin
  • Taxanes: e.g., paclitaxel
  • Thalidomide
• Targeted agents
  • Protein kinase inhibitors
    • BTK inhibitors: e.g., ibrutinib
    • Tyrosine-kinase inhibitors: e.g., nilotinib, alectinib
  • HDAC inhibitors
  • Monoclonal antibodies: e.g., rituximab
• Cancer immunotherapy: immune checkpoint inhibitors, CAR T-cell therapy
• Radiation therapy: e.g., radiation for breast cancer

Management

Management is similar to that for patients without cancer.

• General measures
  • Obtain 12-lead ECG and echocardiogram as needed.
  • Electrolyte repletion as indicated
  • Consider alternative cancer therapies. ^[5]
• Symptomatic bradycardia or high-risk AV block
  • Atropine, pacemaker
  • See also “Management of bradycardia” and “Management of AV block.”
• Management of atrial fibrillation: rate control, anticoagulation
• Tachyarrhythmias
  • Beta blockers: e.g., metoprolol, atenolol
  • See also “Management of SVT” and “Initial management of ventricular tachycardia.”

QT prolongation ^[5][50]

• Associated cancer therapies
  • HDAC inhibitors: e.g., vorinostat
  • Tyrosine kinase inhibitors: e.g., lapatinib, nilotinib
  • BRAF inhibitors: e.g., vemurafenib
• Diagnostics: 12-lead ECG demonstrating ↑ QTc interval (≥ 450 ms)
• Management
  • Stop other QT-prolonging drugs, e.g., ondansetron.
  • Treat hypokalemia and hypomagnesemia.
  • Stop cancer therapy if QTc is > 500 ms.
  • Manage torsades de pointes as indicated.

Hypertension ^[5]

• Associated cancer therapies
  • Proteasome inhibitors: e.g., carfilzomib
  • VEGFR tyrosine kinase inhibitors: e.g., sorafenib, sunitinib
  • Monoclonal antibodies: e.g., bevacizumab
• Management
  • Goal BP < 140/90 mm Hg
  • Preferred initial agent: ACEI
  • Often requires > 1 antihypertensive agent
  • See also “Management of hypertension.”

Interstitial pneumonitis related to cancer therapy ^{[7][11][51][52]}

• Associated cancer therapies
  • Chemotherapy: e.g., bleomycin, gemcitabine
  • Targeted therapy: e.g., rituximab
  • Cancer immunotherapy: e.g., immune checkpoint inhibitors
  • Radiation therapy: See also “Radiation pneumonitis.”
• Management
  • See “Diagnostics for interstitial lung diseases” for details on confirming the diagnosis.
  • Discontinue the causative cancer therapy.
  • Consider systemic glucocorticoids.

Other pulmonary complications ^[7][51][52]

• Bronchospasm: e.g., due to bleomycin, gemcitabine, or trastuzumab ^[7][51][52]
• ARDS: e.g., due to gemcitabine ^[7]
• Pulmonary eosinophilia: e.g., due to bleomycin ^[51]
• Cryptogenic organizing pneumonia: e.g., due to bleomycin ^[51]

Acute kidney injury (AKI) ^[53][54]

Associated cancer therapies ^[53][54]

• Prerenal AKI
  • Calcineurin inhibitors
  • Interleukin-2
  • HSCT ^[53]
• Intrinsic AKI
  • Cisplatin ^[55]
  • Ifosfamide
  • Mitomycin C
  • Interferon alpha
  • Immune checkpoint inhibitors ^[11]
• Postrenal AKI
  • Methotrexate ^[53]

Chemotherapy for poorly differentiated lymphoma or leukemia can cause tumor lysis syndrome. ^[54]

Management

• See “Diagnostics for acute kidney injury.”
• Discontinue nephrotoxic medications.
• Initiate treatment for the underlying cause of AKI.

Thrombotic microangiopathy ^[56][57]

• Associated cancer therapies
  • Mitomycin C
  • Gemcitabine
• Management
  • Confirm the diagnosis using BMP, CBC, and blood smear.
  • Management includes dialysis and plasmapheresis.
  • For details on diagnostics and treatment, see:
    • Thrombotic thrombocytopenic purpura
    • Hemolytic uremic syndrome

Cancer therapy-related hemorrhagic cystitis ^[58][59]

Associated cancer therapies

• Chemotherapy
  • Cyclophosphamide
  • Ifosfamide
• Radiation therapy: See also “Radiation-induced cystitis.”

Diagnostics

• Urinalysis to confirm hematuria
• Urine culture to rule out infection
• Cystoscopy may be considered to exclude other causes of lower urinary tract bleeding.
• CT urography may be considered to rule out upper urinary tract bleeding.

Management

Varies based on severity and may include:

• Hydration (oral or IV fluids)
• Cystoscopy for clot extraction
• Continuous bladder irrigation
• pRBC transfusion

Cancer therapy-induced peripheral neuropathy ^[8]

• Associated cancer therapies
  • Platinum-based agents: e.g., cisplatin
  • Taxanes: e.g., docetaxel
  • Vinca alkaloids: e.g., vincristine
  • Bortezomib
• Diagnostics: See “Diagnostics for polyneuropathy.”
• Management
  • Nonpharmacological treatment (e.g., exercise, self-guided cognitive behavioral therapy)
  • Pharmacological treatment of peripheral neuropathy (e.g., SNRIs, anticonvulsants, topical therapy)
  • See also “Treatment of polyneuropathy.”

Acute encephalopathy ^[8]

• Associated cancer therapies
  • Chemotherapy ^[60]
    • Ifosfamide
    • Melphalan
    • Etoposide
  • Radiation therapy: e.g., whole-brain radiotherapy
• Diagnostics
  • Rule out organic causes: e.g., hemorrhagic stroke, ischemic stroke, or CNS infection.
  • See “Symptom-based diagnostic workup for delirium.”
• Management
  • Discontinue therapy.
  • Correct electrolyte abnormalities.

Complications of cancer therapy can start during and persist after treatment, or occur after treatment is concluded. ^[2][61]

Infertility ^[2][9]

• Associated cancer therapies
  • Chemotherapy: e.g., alkylating agents
  • Radiation therapy: pelvic radiation, CNS radiation, total body irradiation
  • Pelvic surgery
• Management
  • For preventative measures, see “Reproductive care for patients with cancer.”
  • For diagnostics and management, see “Infertility.”

Premature menopause ^[2]

• Associated cancer therapies
  • Chemotherapy: e.g., alkylating agents
  • Radiation therapy
  • Oophorectomy
• Management
  • Symptomatic treatment of vasomotor symptoms
    • Nonhormonal drugs: SSRIs, SNRIs, pregabalin
    • Hormone replacement therapy (contraindicated in breast and endometrial cancer)
  • See also “Management of menopause.”

Sexual dysfunction ^[2]

Sexual dysfunction includes decreased libido and erectile dysfunction.

• Associated cancer therapies
  • Hormone therapy
    • Androgen deprivation therapy
    • Aromatase inhibitors
  • Tamoxifen
  • Radiation therapy: See also “Radiation-induced sexual dysfunction.”
  • Pelvic surgery
• Management
  • Counseling
  • Treatment of dyspareunia, e.g., vaginal moisturizers, intravaginal estrogens
  • Treatment of erectile dysfunction, e.g., PDE5 inhibitors

Secondary osteoporosis ^[2][62]

• Associated cancer therapies
  • Hormone therapy
    • Androgen deprivation therapy
    • Aromatase inhibitors
  • Radiation therapy
  • Surgery: oophorectomy, orchiectomy
• Diagnostics
  • DEXA scan
  • Fracture Risk Assessment Tool may underestimate fracture risk in patients receiving aromatase inhibitors for breast cancer. ^[63]
  • See “Diagnostics for osteoporosis.”
• Management of osteoporosis
  • Bone health optimization, including vitamin D and calcium supplementation
  • Pharmacotherapy for osteoporosis, including bisphosphonates

Accelerated coronary artery disease (CAD) ^[6][50]

Associated cancer therapies

• Chemotherapy
  • Alkylating agents
  • Antimetabolites: e.g., 5-fluorouracil
  • Taxanes: e.g., paclitaxel
  • Platinum-based agents: e.g., cisplatin
  • Bleomycin
• Targeted agents
  • Proteasome inhibitors: e.g., carfilzomib
  • mTOR inhibitors: e.g., everolimus
  • Monoclonal antibodies: e.g., bevacizumab
  • Tyrosine kinase inhibitors: e.g., nilotinib
• Cancer immunotherapies
  • Immune checkpoint inhibitors
  • CAR T-cell therapy
• Radiation therapy: e.g., radiation for breast cancer

Management

• For patients with no symptoms or stable angina pectoris, consider indications for CAD diagnostics.
• For patients with known CAD, start or continue management of coronary artery disease.
• For patients with symptoms of acute cardiac ischemia, see “Management of acute coronary syndrome.”

Other long-term adverse effects^[2]

• Chronic pain ^[64][65]
• Cognitive dysfunction, e.g., decline in memory and attention
• Fatigue and malaise ^[66]
• Lymphedema
• Premature aging ^[2]
• Increased risk for second cancers