Browse the corpus

Effects of Cancer Therapy and Survivorship myeloma and cancer of the lung, breast, kidney, and head and neck. Osteolytic bone metastases are usually the cause of e For slowly recurring malignant pleural effusions, repeat hypercalcemia of malignancy in breast cancer and myeloma, thoracentesis is appropriate; for more rapidly recurring although the incidence of hypercalcemia in these patients may pleural effusions, either an indwelling pleural catheter be decreasing with the prophylactic use of bisphosphonates. with intermittent outpatient drainage or pleurodesis is Paraneoplastic production of parathyroid hormone-related used. protein may occur in localized tumors without widespread bone metastases. Lymphomas and breast cancer can cause

myeloma and cancer of the lung, breast, kidney, and head and neck. Osteolytic bone metastases are usually the cause of e For slowly recurring malignant pleural effusions, repeat hypercalcemia of malignancy in breast cancer and myeloma, thoracentesis is appropriate; for more rapidly recurring although the incidence of hypercalcemia in these patients may pleural effusions, either an indwelling pleural catheter be decreasing with the prophylactic use of bisphosphonates. with intermittent outpatient drainage or pleurodesis is Paraneoplastic production of parathyroid hormone-related used. protein may occur in localized tumors without widespread bone metastases. Lymphomas and breast cancer can cause Metabolic Urgencies and hypercalcemia by overproduction of 1,25-dihydroxyvitamin D. Malignancies such as ovarian cancer can produce ectopic par- Emergencies athyroid hormone. Tumor Lysis Syndrome Patients may present with dehydration, acute kidney Tumor lysis syndrome (TLS) is caused when tumor cells injury and nausea, vomiting, constipation, fatigue, polyuria, release their contents into the bloodstream, either spontane- polydipsia, altered mental status, or muscle weakness. ously or as a result of treatment, leading to hyperuricemia, Symptoms depend on both the serum calcium level (more hyperkalemia, hyperphosphatemia, and hypocalcemia. These severe symptoms with calcium > 14 mg/dL [3.5 mmol/L]) and electrolyte abnormalities can lead to acute kidney injury, car- a rapid rate of rise. diac arrhythmias, seizures, and death. TLS is seen most often Patients with severe or symptomatic hypercalcemia in highly proliferative hematologic malignancies such as acute should receive isotonic saline volume expansion. Loop diuret- leukemia and high-grade lymphomas but can develop in ics are not recommended unless kidney failure or heart fail- other cancers. ure is present, in which case volume expansion should The risk of TLS can be categorized based on the volume of precede the administration of loop diuretics to avoid hypoten- cancer mass present; the cell-lysis potential of the cancer; and sion and further kidney injury. Calcitonin increases kidney patient characteristics of preexisting kidney failure, dehydra- excretion of calcium and decreases bone resorption; it can tion, acidosis, hypotension, or nephrotoxin exposure. Patients decrease calcium within several hours in responsive patients. at intermediate risk for TLS can be managed with monitoring Bisphosphonates, such as zoledronic acid, which inhibit bone of laboratory values, hydration, and allopurinol, and those at resorption can lower calcium levels to normal in 50% of high risk should receive intravenous hydration and rasbur- patients in 4 days and in 88% of patients in 10 days. The recep- icase, a urate oxidase enzyme that metabolizes uric acid, tor activator of nuclear factor «B ligand denosumab can be before receiving chemotherapy. There is no clear benefit of considered for patients who do not respond to zoledronic alkalinization to increase uric acid excretion or prevent uric acid. It can be safely used in patients with kidney failure acid nephropathy, particularly given the availability of rasbur- where bisphosphonates may be contraindicated. Effective icase. Alkalinization increases the risk of hyperphosphatemia treatment of the underlying malignancy remains the most and precipitation of calcium phosphate crystals. appropriate means of controlling hypercalcemia. Patients who develop TLS require continuous cardiac monitoring; serum measurement of electrolytes, creatinine, e Patients with severe or symptomatic hypercalcemia and urate every 4 to 6 hours; and correction of electrolyte should receive isotonic saline volume expansion; loop abnormalities. Depending upon the severity, rasburicase can diuretics are not recommended unless kidney failure or be given and patients should receive aggressive hydration if kidney function allows, with the use of a loop diuretic if heart failure is present.

Metabolic Urgencies and hypercalcemia by overproduction of 1,25-dihydroxyvitamin D. Malignancies such as ovarian cancer can produce ectopic par- Emergencies athyroid hormone. Tumor Lysis Syndrome Patients may present with dehydration, acute kidney Tumor lysis syndrome (TLS) is caused when tumor cells injury and nausea, vomiting, constipation, fatigue, polyuria, release their contents into the bloodstream, either spontane- polydipsia, altered mental status, or muscle weakness. ously or as a result of treatment, leading to hyperuricemia, Symptoms depend on both the serum calcium level (more hyperkalemia, hyperphosphatemia, and hypocalcemia. These severe symptoms with calcium > 14 mg/dL [3.5 mmol/L]) and electrolyte abnormalities can lead to acute kidney injury, car- a rapid rate of rise. diac arrhythmias, seizures, and death. TLS is seen most often Patients with severe or symptomatic hypercalcemia in highly proliferative hematologic malignancies such as acute should receive isotonic saline volume expansion. Loop diuret- leukemia and high-grade lymphomas but can develop in ics are not recommended unless kidney failure or heart fail- other cancers. ure is present, in which case volume expansion should The risk of TLS can be categorized based on the volume of precede the administration of loop diuretics to avoid hypoten- cancer mass present; the cell-lysis potential of the cancer; and sion and further kidney injury. Calcitonin increases kidney patient characteristics of preexisting kidney failure, dehydra- excretion of calcium and decreases bone resorption; it can tion, acidosis, hypotension, or nephrotoxin exposure. Patients decrease calcium within several hours in responsive patients. at intermediate risk for TLS can be managed with monitoring Bisphosphonates, such as zoledronic acid, which inhibit bone of laboratory values, hydration, and allopurinol, and those at resorption can lower calcium levels to normal in 50% of high risk should receive intravenous hydration and rasbur- patients in 4 days and in 88% of patients in 10 days. The recep- icase, a urate oxidase enzyme that metabolizes uric acid, tor activator of nuclear factor «B ligand denosumab can be before receiving chemotherapy. There is no clear benefit of considered for patients who do not respond to zoledronic alkalinization to increase uric acid excretion or prevent uric acid. It can be safely used in patients with kidney failure acid nephropathy, particularly given the availability of rasbur- where bisphosphonates may be contraindicated. Effective icase. Alkalinization increases the risk of hyperphosphatemia treatment of the underlying malignancy remains the most and precipitation of calcium phosphate crystals. appropriate means of controlling hypercalcemia. Patients who develop TLS require continuous cardiac monitoring; serum measurement of electrolytes, creatinine, e Patients with severe or symptomatic hypercalcemia and urate every 4 to 6 hours; and correction of electrolyte should receive isotonic saline volume expansion; loop abnormalities. Depending upon the severity, rasburicase can diuretics are not recommended unless kidney failure or be given and patients should receive aggressive hydration if kidney function allows, with the use of a loop diuretic if heart failure is present. needed to improve urinary output. Patients may require renal ¢ Calcitonin is recommended for immediate management of replacement therapy for severe oliguria or anuria, persistent symptomatic hypercalcemia and bisphosphonates are pre- hyperkalemia, symptomatic hypocalcemia, or a calcium- ferred to denosumab for longer-term control; treatment of phosphate product greater than or equal to 70 mg?/dL?. the underlying cancer is the definitive management.

needed to improve urinary output. Patients may require renal ¢ Calcitonin is recommended for immediate management of replacement therapy for severe oliguria or anuria, persistent symptomatic hypercalcemia and bisphosphonates are pre- hyperkalemia, symptomatic hypocalcemia, or a calcium- ferred to denosumab for longer-term control; treatment of phosphate product greater than or equal to 70 mg?/dL?. the underlying cancer is the definitive management. e Tumor lysis syndrome should be treated with rasbur- icase and aggressive hydration if kidney function allows; patients require continuous cardiac monitoring and Effects of Cancer Therapy measurement of electrolyte, creatinine, and urate levels and Survivorship every 4 to 6 hours. Effects of Cancer Therapy Hypercalcemia of Malignancy Hematologic Toxicity Hypercalcemia of malignancy occurs in 20% to 30% of patients Myelosuppression remains the major toxicity of many tradi- with advanced cancer. It is most frequent in patients with tional chemotherapeutic agents. 44

Effects of Cancer Therapy and Survivorship Neutropenia and Fever Anemia and Thrombocytopenia Neutropenia typically occurs 5 to 15 days after chemother- Anemia in patients with cancer may be related to chronic apy administration. Serious infectious complications are inflammation, bone marrow suppression, blood loss, and more likely with increasing severity (absolute neutrophil chemotherapy. Erythrocyte transfusions and erythropoietin count below 500/uL [0.5 x 10°/L]) and duration of neutrope- administration are sometimes required. Erythropoietin has nia. Prompt evaluation is critical and should include assess- been associated with more rapid cancer progression and ment for a source and appropriate cultures immediately increased risk of venous thromboembolism. This has prompted followed by administration of an empiric, broad-spectrum increased regulation and a significant decrease in the use of antibiotic. Antibiotic monotherapy is typically an antipseu- erythropoietin therapy in patients with cancer, particularly for domonal B-lactam agent such as cefepime; a carbapenem, those receiving curative or adjuvant treatments. such as meropenem; or piperacillin/tazobactam. Other anti- Thrombocytopenia is generally managed with platelet microbials, such as fluoroquinolones, or vancomycin, can be transfusions, when needed, and appropriate chemotherapy added if antimicrobial resistance is suspected or for manage- dose reductions and delays (see Hematology). ment of patients with shock or pneumonia. Specific anaero- bic therapy (clindamycin or metronidazole) is not generally Nausea and Vomiting needed unless an anaerobic source is suspected. Selected Although nausea and vomiting are common adverse effects of patients without significant comorbidities who are stable chemotherapy, their incidence and severity have been mark- and adherent, and in whom a short duration of neutropenia edly reduced by antiemetic medications. For patients receiving is anticipated, can be treated as an outpatient with intravenous moderate to severely emetogenic drugs, administration of or oral antibiotics. In these patients, guidelines recommend serotonin receptor antagonists (such as ondansetron or the the combination of a fluoroquinolone (i.e., ciprofloxacin or longer-acting palonosetron) in combination with high-dose levofloxacin) plus amoxicillin/clavulanate as first-line ther- glucocorticoid therapy is standard. Neurokinin-1 receptor apy because this combination is supported by the largest blockers (such as aprepitant and netupitant) should also be and most convincing body of evidence for safety and added for those receiving severely emetogenic therapies. The effectiveness. antipsychotic agent olanzapine may also be helpful for reduc- The prophylactic use of granulocyte colony-stimulating ing emesis. Anticipatory nausea and vomiting may occur in factor or granulocyte-macrophage colony-stimulating factor patients who experienced these symptoms during prior che- reduces the risk of febrile neutropenia. These medications may motherapy cycles. Excellent control of nausea and vomiting be given to patients receiving regimens associated with a high during the first few cycles of chemotherapy can prevent antici- risk of this complication or as secondary prophylaxis in patory symptoms. Behavioral therapy or benzodiazepines can patients with a previous episode of neutropenic fever. Growth be prescribed for patients who experience anticipatory nausea factors are not routinely used in the treatment of patients with and vomiting. neutropenic fever but can be considered in those who are at high risk including expected prolonged (> 10 days) and pro- Dermatologic Effects found (<0.1 x 10°/L) neutropenia, aged 65 years and older, Alopecia, although not invariable, is the most common cuta- uncontrolled primary disease, pneumonia, sepsis syndrome, neous adverse effect. Fluoropyrimidines (5-fluorouracil and invasive fungal infection, or hospitalization at the time of fever capecitabine) are associated with palmar-plantar erythro- development. dysesthesia (hand-foot syndrome), characterized as redness, peeling, and tenderness of the palms and soles. Epidermal

Neutropenia and Fever Anemia and Thrombocytopenia Neutropenia typically occurs 5 to 15 days after chemother- Anemia in patients with cancer may be related to chronic apy administration. Serious infectious complications are inflammation, bone marrow suppression, blood loss, and more likely with increasing severity (absolute neutrophil chemotherapy. Erythrocyte transfusions and erythropoietin count below 500/uL [0.5 x 10°/L]) and duration of neutrope- administration are sometimes required. Erythropoietin has nia. Prompt evaluation is critical and should include assess- been associated with more rapid cancer progression and ment for a source and appropriate cultures immediately increased risk of venous thromboembolism. This has prompted followed by administration of an empiric, broad-spectrum increased regulation and a significant decrease in the use of antibiotic. Antibiotic monotherapy is typically an antipseu- erythropoietin therapy in patients with cancer, particularly for domonal B-lactam agent such as cefepime; a carbapenem, those receiving curative or adjuvant treatments. such as meropenem; or piperacillin/tazobactam. Other anti- Thrombocytopenia is generally managed with platelet microbials, such as fluoroquinolones, or vancomycin, can be transfusions, when needed, and appropriate chemotherapy added if antimicrobial resistance is suspected or for manage- dose reductions and delays (see Hematology). ment of patients with shock or pneumonia. Specific anaero- bic therapy (clindamycin or metronidazole) is not generally Nausea and Vomiting needed unless an anaerobic source is suspected. Selected Although nausea and vomiting are common adverse effects of patients without significant comorbidities who are stable chemotherapy, their incidence and severity have been mark- and adherent, and in whom a short duration of neutropenia edly reduced by antiemetic medications. For patients receiving is anticipated, can be treated as an outpatient with intravenous moderate to severely emetogenic drugs, administration of or oral antibiotics. In these patients, guidelines recommend serotonin receptor antagonists (such as ondansetron or the the combination of a fluoroquinolone (i.e., ciprofloxacin or longer-acting palonosetron) in combination with high-dose levofloxacin) plus amoxicillin/clavulanate as first-line ther- glucocorticoid therapy is standard. Neurokinin-1 receptor apy because this combination is supported by the largest blockers (such as aprepitant and netupitant) should also be and most convincing body of evidence for safety and added for those receiving severely emetogenic therapies. The effectiveness. antipsychotic agent olanzapine may also be helpful for reduc- The prophylactic use of granulocyte colony-stimulating ing emesis. Anticipatory nausea and vomiting may occur in factor or granulocyte-macrophage colony-stimulating factor patients who experienced these symptoms during prior che- reduces the risk of febrile neutropenia. These medications may motherapy cycles. Excellent control of nausea and vomiting be given to patients receiving regimens associated with a high during the first few cycles of chemotherapy can prevent antici- risk of this complication or as secondary prophylaxis in patory symptoms. Behavioral therapy or benzodiazepines can patients with a previous episode of neutropenic fever. Growth be prescribed for patients who experience anticipatory nausea factors are not routinely used in the treatment of patients with and vomiting. neutropenic fever but can be considered in those who are at high risk including expected prolonged (> 10 days) and pro- Dermatologic Effects found (<0.1 x 10°/L) neutropenia, aged 65 years and older, Alopecia, although not invariable, is the most common cuta- uncontrolled primary disease, pneumonia, sepsis syndrome, neous adverse effect. Fluoropyrimidines (5-fluorouracil and invasive fungal infection, or hospitalization at the time of fever capecitabine) are associated with palmar-plantar erythro- development. dysesthesia (hand-foot syndrome), characterized as redness, peeling, and tenderness of the palms and soles. Epidermal HVC e Most patients with neutropenic fever should be man- growth factor receptor inhibitors, such as erlotinib and gefi-

Neutropenia and Fever Anemia and Thrombocytopenia Neutropenia typically occurs 5 to 15 days after chemother- Anemia in patients with cancer may be related to chronic apy administration. Serious infectious complications are inflammation, bone marrow suppression, blood loss, and more likely with increasing severity (absolute neutrophil chemotherapy. Erythrocyte transfusions and erythropoietin count below 500/uL [0.5 x 10°/L]) and duration of neutrope- administration are sometimes required. Erythropoietin has nia. Prompt evaluation is critical and should include assess- been associated with more rapid cancer progression and ment for a source and appropriate cultures immediately increased risk of venous thromboembolism. This has prompted followed by administration of an empiric, broad-spectrum increased regulation and a significant decrease in the use of antibiotic. Antibiotic monotherapy is typically an antipseu- erythropoietin therapy in patients with cancer, particularly for domonal B-lactam agent such as cefepime; a carbapenem, those receiving curative or adjuvant treatments. such as meropenem; or piperacillin/tazobactam. Other anti- Thrombocytopenia is generally managed with platelet microbials, such as fluoroquinolones, or vancomycin, can be transfusions, when needed, and appropriate chemotherapy added if antimicrobial resistance is suspected or for manage- dose reductions and delays (see Hematology). ment of patients with shock or pneumonia. Specific anaero- bic therapy (clindamycin or metronidazole) is not generally Nausea and Vomiting needed unless an anaerobic source is suspected. Selected Although nausea and vomiting are common adverse effects of patients without significant comorbidities who are stable chemotherapy, their incidence and severity have been mark- and adherent, and in whom a short duration of neutropenia edly reduced by antiemetic medications. For patients receiving is anticipated, can be treated as an outpatient with intravenous moderate to severely emetogenic drugs, administration of or oral antibiotics. In these patients, guidelines recommend serotonin receptor antagonists (such as ondansetron or the the combination of a fluoroquinolone (i.e., ciprofloxacin or longer-acting palonosetron) in combination with high-dose levofloxacin) plus amoxicillin/clavulanate as first-line ther- glucocorticoid therapy is standard. Neurokinin-1 receptor apy because this combination is supported by the largest blockers (such as aprepitant and netupitant) should also be and most convincing body of evidence for safety and added for those receiving severely emetogenic therapies. The effectiveness. antipsychotic agent olanzapine may also be helpful for reduc- The prophylactic use of granulocyte colony-stimulating ing emesis. Anticipatory nausea and vomiting may occur in factor or granulocyte-macrophage colony-stimulating factor patients who experienced these symptoms during prior che- reduces the risk of febrile neutropenia. These medications may motherapy cycles. Excellent control of nausea and vomiting be given to patients receiving regimens associated with a high during the first few cycles of chemotherapy can prevent antici- risk of this complication or as secondary prophylaxis in patory symptoms. Behavioral therapy or benzodiazepines can patients with a previous episode of neutropenic fever. Growth be prescribed for patients who experience anticipatory nausea factors are not routinely used in the treatment of patients with and vomiting. neutropenic fever but can be considered in those who are at high risk including expected prolonged (> 10 days) and pro- Dermatologic Effects found (<0.1 x 10°/L) neutropenia, aged 65 years and older, Alopecia, although not invariable, is the most common cuta- uncontrolled primary disease, pneumonia, sepsis syndrome, neous adverse effect. Fluoropyrimidines (5-fluorouracil and invasive fungal infection, or hospitalization at the time of fever capecitabine) are associated with palmar-plantar erythro- development. dysesthesia (hand-foot syndrome), characterized as redness, peeling, and tenderness of the palms and soles. Epidermal HVC e Most patients with neutropenic fever should be man- growth factor receptor inhibitors, such as erlotinib and gefi- aged with monotherapy with an anti-pseudomonal tinib are associated with pustular acneiform eruptions.

Neutropenia and Fever Anemia and Thrombocytopenia Neutropenia typically occurs 5 to 15 days after chemother- Anemia in patients with cancer may be related to chronic apy administration. Serious infectious complications are inflammation, bone marrow suppression, blood loss, and more likely with increasing severity (absolute neutrophil chemotherapy. Erythrocyte transfusions and erythropoietin count below 500/uL [0.5 x 10°/L]) and duration of neutrope- administration are sometimes required. Erythropoietin has nia. Prompt evaluation is critical and should include assess- been associated with more rapid cancer progression and ment for a source and appropriate cultures immediately increased risk of venous thromboembolism. This has prompted followed by administration of an empiric, broad-spectrum increased regulation and a significant decrease in the use of antibiotic. Antibiotic monotherapy is typically an antipseu- erythropoietin therapy in patients with cancer, particularly for domonal B-lactam agent such as cefepime; a carbapenem, those receiving curative or adjuvant treatments. such as meropenem; or piperacillin/tazobactam. Other anti- Thrombocytopenia is generally managed with platelet microbials, such as fluoroquinolones, or vancomycin, can be transfusions, when needed, and appropriate chemotherapy added if antimicrobial resistance is suspected or for manage- dose reductions and delays (see Hematology). ment of patients with shock or pneumonia. Specific anaero- bic therapy (clindamycin or metronidazole) is not generally Nausea and Vomiting needed unless an anaerobic source is suspected. Selected Although nausea and vomiting are common adverse effects of patients without significant comorbidities who are stable chemotherapy, their incidence and severity have been mark- and adherent, and in whom a short duration of neutropenia edly reduced by antiemetic medications. For patients receiving is anticipated, can be treated as an outpatient with intravenous moderate to severely emetogenic drugs, administration of or oral antibiotics. In these patients, guidelines recommend serotonin receptor antagonists (such as ondansetron or the the combination of a fluoroquinolone (i.e., ciprofloxacin or longer-acting palonosetron) in combination with high-dose levofloxacin) plus amoxicillin/clavulanate as first-line ther- glucocorticoid therapy is standard. Neurokinin-1 receptor apy because this combination is supported by the largest blockers (such as aprepitant and netupitant) should also be and most convincing body of evidence for safety and added for those receiving severely emetogenic therapies. The effectiveness. antipsychotic agent olanzapine may also be helpful for reduc- The prophylactic use of granulocyte colony-stimulating ing emesis. Anticipatory nausea and vomiting may occur in factor or granulocyte-macrophage colony-stimulating factor patients who experienced these symptoms during prior che- reduces the risk of febrile neutropenia. These medications may motherapy cycles. Excellent control of nausea and vomiting be given to patients receiving regimens associated with a high during the first few cycles of chemotherapy can prevent antici- risk of this complication or as secondary prophylaxis in patory symptoms. Behavioral therapy or benzodiazepines can patients with a previous episode of neutropenic fever. Growth be prescribed for patients who experience anticipatory nausea factors are not routinely used in the treatment of patients with and vomiting. neutropenic fever but can be considered in those who are at high risk including expected prolonged (> 10 days) and pro- Dermatologic Effects found (<0.1 x 10°/L) neutropenia, aged 65 years and older, Alopecia, although not invariable, is the most common cuta- uncontrolled primary disease, pneumonia, sepsis syndrome, neous adverse effect. Fluoropyrimidines (5-fluorouracil and invasive fungal infection, or hospitalization at the time of fever capecitabine) are associated with palmar-plantar erythro- development. dysesthesia (hand-foot syndrome), characterized as redness, peeling, and tenderness of the palms and soles. Epidermal HVC e Most patients with neutropenic fever should be man- growth factor receptor inhibitors, such as erlotinib and gefi- aged with monotherapy with an anti-pseudomonal tinib are associated with pustular acneiform eruptions. B-lactam agent. Monoclonal antibodies against epidermal growth factor recep- tor (cetuximab and panitumumab) are often associated with ¢ The prophylactic use of granulocyte colony-stimulating more severe acneiform eruption. factor or granulocyte-macrophage colony-stimulating factor may be given to patients receiving regimens asso- ciated with a high risk of this complication or as sec- Disorders of Pulmonary Function ondary prophylaxis in patients with a previous episode Bleomycin, nitrosoureas, and gemcitabine may have the

B-lactam agent. Monoclonal antibodies against epidermal growth factor recep- tor (cetuximab and panitumumab) are often associated with ¢ The prophylactic use of granulocyte colony-stimulating more severe acneiform eruption. factor or granulocyte-macrophage colony-stimulating factor may be given to patients receiving regimens asso- ciated with a high risk of this complication or as sec- Disorders of Pulmonary Function ondary prophylaxis in patients with a previous episode Bleomycin, nitrosoureas, and gemcitabine may have the of neutropenic fever. strongest associations with pulmonary toxicity, but many other agents have toxicity potential. Additionally, various HVC ¢ Growth factors are not routinely used in the treatment monoclonal antibodies and targeted therapies can be associ- of patients with neutropenic fever unless the patient ated with pulmonary toxicities, including rituximab, trastu- has severe neutropenia (<100/uL [0.1 x 10°/L]) zumab, cetuximab, and erlotinib. expected to last more than 10 days or has other high- Radiation therapy can be associated with pneumonitis, risk features. typically occurring within 1 to 3 months of treatment and may 45

Effects of Cancer Therapy and Survivorship lead to the development of radiation fibrosis. See Pulmonary and secondary malignancies; monitoring for late-organ dys- and Critical Care Medicine for further discussion of disorders function; and helping patients cope with the psychological, of pulmonary function related to chemotherapy. sexual, vocational, and other effects of treatment. An initial treatment plan for cancer may be based not only on providing Disorders of Genitourinary and Kidney Function the highest probability of cure but also on a strategy to reduce Cisplatin is the most common chemotherapy affecting kidney the risk of long-term complications. function and is associated with acute tubular necrosis. The risk is reduced with the use of aggressive hydration. Both Late Effects of Cancer Therapy ifosfamide and cyclophosphamide, in high doses, may cause Effects on Bone Health hemorrhagic cystitis. Hemolytic uremic syndrome is most Bone loss occurs at an increased rate in cancer survivors who commonly associated with mitomycin and gemcitabine. have taken long-term glucocorticoids and in women who have undergone surgical, irradiation, or chemotherapy-induced Neurologic Toxicity premature menopause or who are taking aromatase inhibitors Peripheral neuropathy is a frequent toxicity of platinum for breast cancer. Men treated for prostate cancer with andro- agents, taxanes, vinca alkaloids, and proteasome inhibitors. gen deprivation therapy are also at increased risk for osteopo- Oxaliplatin causes a transient hypersensitivity to cold—patients rosis. Multiple myeloma may cause generalized bone loss as must avoid eating, drinking, or even touching cold items for well as lytic bone disease. Assessment of bone density and several days after infusions—as well as a non-temperature- treatment or prophylaxis should be considered to reduce the dependent persistent peripheral neuropathy. risk of fracture. Treatment commonly includes routine supple-

agents, taxanes, vinca alkaloids, and proteasome inhibitors. gen deprivation therapy are also at increased risk for osteopo- Oxaliplatin causes a transient hypersensitivity to cold—patients rosis. Multiple myeloma may cause generalized bone loss as must avoid eating, drinking, or even touching cold items for well as lytic bone disease. Assessment of bone density and several days after infusions—as well as a non-temperature- treatment or prophylaxis should be considered to reduce the dependent persistent peripheral neuropathy. risk of fracture. Treatment commonly includes routine supple- Rituximab, along with other immunosuppressive agents, ments of vitamin D and calcium (while monitoring serum rarely has been associated with progressive multifocal leu- calcium levels) and bisphosphonates or denosumab. Vigilance koencephalopathy. 5-Fluorouracil and high-dose cytosine ara- is required to detect bisphosphonate complications such as binoside are associated with cerebellar toxicity. The reversible osteonecrosis of the jaw (Figure 11) and atypical subtrochan- posterior encephalopathy syndrome has been linked to che- teric spiral fractures of the femur. motherapy that targets vascular endothelial growth factor, such as bevacizumab or sunitinib. Disorders of Cardiac Function Because whole-brain irradiation can cause long-term Doxorubicin and other anthracyclines can cause irreversible impairment of cognitive function, focused high-dose irradia- cardiomyopathy; the risk increases with cumulative dosing. tion (gamma knife or stereotactic radiosurgery) has become the Trastuzumab can also induce dose-independent cardiomyopa- preferred treatment for patients with limited brain metastases. thy that is usually reversible; the risk increases when trastu- zamab is combined with anthracyclines. Fluoropyrimidines Toxicities Related to Immune Dysregulation have been associated with coronary spasm and ischemia dur- With the widespread use of checkpoint inhibitors, patients ing administration. with cancer are at risk for toxicities associated with the The tyrosine kinase inhibitors nilotinib and ponatinib are

motherapy that targets vascular endothelial growth factor, such as bevacizumab or sunitinib. Disorders of Cardiac Function Because whole-brain irradiation can cause long-term Doxorubicin and other anthracyclines can cause irreversible impairment of cognitive function, focused high-dose irradia- cardiomyopathy; the risk increases with cumulative dosing. tion (gamma knife or stereotactic radiosurgery) has become the Trastuzumab can also induce dose-independent cardiomyopa- preferred treatment for patients with limited brain metastases. thy that is usually reversible; the risk increases when trastu- zamab is combined with anthracyclines. Fluoropyrimidines Toxicities Related to Immune Dysregulation have been associated with coronary spasm and ischemia dur- With the widespread use of checkpoint inhibitors, patients ing administration. with cancer are at risk for toxicities associated with the The tyrosine kinase inhibitors nilotinib and ponatinib are induction of autoimmunity. Antibodies such as ipilimumab; associated with coronary insufficiency, and dasatinib is associ- pembrolizumab and nivolumab; and atezolizumab, dur- ated with pulmonary hypertension. The anti-vascular valumab, and avelumab; are associated with immune-related endothelial growth factor antibody bevacizumab is associated colitis, pneumonitis, hepatitis, dermatitis, endocrinopathies with hypertension as well as an increased risk of coronary and (hypophysitis, thyroiditis, and adrenalitis) and neuritis. other vascular events. These toxicities require prompt recognition, sometimes tem- porary or permanent cessation of immunotherapy, and often glucocorticoid therapy as well as hormone replacement, if indicated. e Standard antiemetic treatment of patients taking severe emetogenic chemotherapy drugs is a serotonin receptor antagonist (ondansetron or palonosetron), a high-dose glucocorticoid, a neurokinin-1 receptor blocker (aprepi- tant or netupitant), and possibly olanzapine.

These toxicities require prompt recognition, sometimes tem- porary or permanent cessation of immunotherapy, and often glucocorticoid therapy as well as hormone replacement, if indicated. e Standard antiemetic treatment of patients taking severe emetogenic chemotherapy drugs is a serotonin receptor antagonist (ondansetron or palonosetron), a high-dose glucocorticoid, a neurokinin-1 receptor blocker (aprepi- tant or netupitant), and possibly olanzapine. Survivorship Issues Survivorship embodies the care that follows patients on com- pletion of their treatments, including screening for recurrence FIGURE 11. Osteonecrosis of the jaw secondary to bisphosphonate therapy. 46

Bibliography Monitoring for and management of cardiac complications Survivorship Care Plan in cancer survivors is discussed in Cardiovascular Medicine. Providing patients with a prescription for survivorship is an important responsibility of oncologists. At the end of treat- Sexual Function and Fertility ment, patients receive a document summarizing their diagno- Surgery, irradiation, and chemotherapy may all affect sexual sis, stage, and treatment details, along with recommended function and fertility of both men and women. Altered body follow-up. Recommendations can include surveillance for image after breast surgery and the generalized fatigue associ- cancer recurrence, healthy lifestyle modification, and strategy ated with irradiation or chemotherapy may reduce libido. to reduce or prevent the late effects of cancer treatment. Anxiety and depression further diminish interest in sex. Cancer survivors should, at a minimum, have age- and Counseling and support groups may be helpful. gender-appropriate cancer screening. Secondary malignancies In women, premature menopause and infertility can may develop in cancer survivors owing to a preexisting genetic result from both pelvic radiotherapy and chemotherapy, par- predisposition, a “field” effect from previous carcinogen expo- ticularly with alkylating agents. Estrogen is the most effective sure, or late effects of previous cancer treatments. Patients with therapy for vasomotor symptoms related to premature meno- identified genetic mutations with an increased risk of additional pause. For women with an intact uterus, estrogen should be malignancies should have genetics counseling. Patients with combined with progestin. Estrogen replacement therapy is smoking-related head and neck cancer are prone to second head contraindicated in patients with breast and endometrial can- and neck cancers, as well as lung and esophageal cancers. cer. Risk factors for infertility relate to the dose and duration of Patients exposed to chemotherapy with alkylating agents have chemotherapy as well as patient age. Consultation with fertil- an increased risk of myelodysplastic syndromes and acute leuke- ity experts should be offered to women who desire future mia. Radiation to the neck can be associated with hypothyroid- childbearing; egg and embryo harvests may be options. ism as well as thyroid cancer years later. Women receiving Fertility evaluations can often be done on an emergency basis, radiation to the mediastinum for Hodgkin lymphoma and other so delay in the initiation of definitive cancer treatment is mini- cancers have a marked increase of breast cancer, particularly if mized. Men may consider semen cryopreservation. they were treated in adolescence and early adulthood, with the Tamoxifen, aromatase inhibitors, and ovarian suppres- increased risk beginning about 8 years after treatment. Screening sion may cause menopausal symptoms, decreased libido, and MRI, mammography, or a combination of both modalities is vaginal dryness. Men commonly experience erectile dysfunc- recommended for these patients beginning at age 25 years or tion after prostate surgery or irradiation, and androgen depri- 8 years after completing radiation therapy, whichever occurs last. vation therapy suppresses libido.

Monitoring for and management of cardiac complications Survivorship Care Plan in cancer survivors is discussed in Cardiovascular Medicine. Providing patients with a prescription for survivorship is an important responsibility of oncologists. At the end of treat- Sexual Function and Fertility ment, patients receive a document summarizing their diagno- Surgery, irradiation, and chemotherapy may all affect sexual sis, stage, and treatment details, along with recommended function and fertility of both men and women. Altered body follow-up. Recommendations can include surveillance for image after breast surgery and the generalized fatigue associ- cancer recurrence, healthy lifestyle modification, and strategy ated with irradiation or chemotherapy may reduce libido. to reduce or prevent the late effects of cancer treatment. Anxiety and depression further diminish interest in sex. Cancer survivors should, at a minimum, have age- and Counseling and support groups may be helpful. gender-appropriate cancer screening. Secondary malignancies In women, premature menopause and infertility can may develop in cancer survivors owing to a preexisting genetic result from both pelvic radiotherapy and chemotherapy, par- predisposition, a “field” effect from previous carcinogen expo- ticularly with alkylating agents. Estrogen is the most effective sure, or late effects of previous cancer treatments. Patients with therapy for vasomotor symptoms related to premature meno- identified genetic mutations with an increased risk of additional pause. For women with an intact uterus, estrogen should be malignancies should have genetics counseling. Patients with combined with progestin. Estrogen replacement therapy is smoking-related head and neck cancer are prone to second head contraindicated in patients with breast and endometrial can- and neck cancers, as well as lung and esophageal cancers. cer. Risk factors for infertility relate to the dose and duration of Patients exposed to chemotherapy with alkylating agents have chemotherapy as well as patient age. Consultation with fertil- an increased risk of myelodysplastic syndromes and acute leuke- ity experts should be offered to women who desire future mia. Radiation to the neck can be associated with hypothyroid- childbearing; egg and embryo harvests may be options. ism as well as thyroid cancer years later. Women receiving Fertility evaluations can often be done on an emergency basis, radiation to the mediastinum for Hodgkin lymphoma and other so delay in the initiation of definitive cancer treatment is mini- cancers have a marked increase of breast cancer, particularly if mized. Men may consider semen cryopreservation. they were treated in adolescence and early adulthood, with the Tamoxifen, aromatase inhibitors, and ovarian suppres- increased risk beginning about 8 years after treatment. Screening sion may cause menopausal symptoms, decreased libido, and MRI, mammography, or a combination of both modalities is vaginal dryness. Men commonly experience erectile dysfunc- recommended for these patients beginning at age 25 years or tion after prostate surgery or irradiation, and androgen depri- 8 years after completing radiation therapy, whichever occurs last. vation therapy suppresses libido. Cognitive Decline e A “prescription for survivorship” provides the patient

Monitoring for and management of cardiac complications Survivorship Care Plan in cancer survivors is discussed in Cardiovascular Medicine. Providing patients with a prescription for survivorship is an important responsibility of oncologists. At the end of treat- Sexual Function and Fertility ment, patients receive a document summarizing their diagno- Surgery, irradiation, and chemotherapy may all affect sexual sis, stage, and treatment details, along with recommended function and fertility of both men and women. Altered body follow-up. Recommendations can include surveillance for image after breast surgery and the generalized fatigue associ- cancer recurrence, healthy lifestyle modification, and strategy ated with irradiation or chemotherapy may reduce libido. to reduce or prevent the late effects of cancer treatment. Anxiety and depression further diminish interest in sex. Cancer survivors should, at a minimum, have age- and Counseling and support groups may be helpful. gender-appropriate cancer screening. Secondary malignancies In women, premature menopause and infertility can may develop in cancer survivors owing to a preexisting genetic result from both pelvic radiotherapy and chemotherapy, par- predisposition, a “field” effect from previous carcinogen expo- ticularly with alkylating agents. Estrogen is the most effective sure, or late effects of previous cancer treatments. Patients with therapy for vasomotor symptoms related to premature meno- identified genetic mutations with an increased risk of additional pause. For women with an intact uterus, estrogen should be malignancies should have genetics counseling. Patients with combined with progestin. Estrogen replacement therapy is smoking-related head and neck cancer are prone to second head contraindicated in patients with breast and endometrial can- and neck cancers, as well as lung and esophageal cancers. cer. Risk factors for infertility relate to the dose and duration of Patients exposed to chemotherapy with alkylating agents have chemotherapy as well as patient age. Consultation with fertil- an increased risk of myelodysplastic syndromes and acute leuke- ity experts should be offered to women who desire future mia. Radiation to the neck can be associated with hypothyroid- childbearing; egg and embryo harvests may be options. ism as well as thyroid cancer years later. Women receiving Fertility evaluations can often be done on an emergency basis, radiation to the mediastinum for Hodgkin lymphoma and other so delay in the initiation of definitive cancer treatment is mini- cancers have a marked increase of breast cancer, particularly if mized. Men may consider semen cryopreservation. they were treated in adolescence and early adulthood, with the Tamoxifen, aromatase inhibitors, and ovarian suppres- increased risk beginning about 8 years after treatment. Screening sion may cause menopausal symptoms, decreased libido, and MRI, mammography, or a combination of both modalities is vaginal dryness. Men commonly experience erectile dysfunc- recommended for these patients beginning at age 25 years or tion after prostate surgery or irradiation, and androgen depri- 8 years after completing radiation therapy, whichever occurs last. vation therapy suppresses libido. Cognitive Decline e A “prescription for survivorship” provides the patient Short-term and long-term declines in cognitive function are a with recommendations regarding surveillance for can-

Monitoring for and management of cardiac complications Survivorship Care Plan in cancer survivors is discussed in Cardiovascular Medicine. Providing patients with a prescription for survivorship is an important responsibility of oncologists. At the end of treat- Sexual Function and Fertility ment, patients receive a document summarizing their diagno- Surgery, irradiation, and chemotherapy may all affect sexual sis, stage, and treatment details, along with recommended function and fertility of both men and women. Altered body follow-up. Recommendations can include surveillance for image after breast surgery and the generalized fatigue associ- cancer recurrence, healthy lifestyle modification, and strategy ated with irradiation or chemotherapy may reduce libido. to reduce or prevent the late effects of cancer treatment. Anxiety and depression further diminish interest in sex. Cancer survivors should, at a minimum, have age- and Counseling and support groups may be helpful. gender-appropriate cancer screening. Secondary malignancies In women, premature menopause and infertility can may develop in cancer survivors owing to a preexisting genetic result from both pelvic radiotherapy and chemotherapy, par- predisposition, a “field” effect from previous carcinogen expo- ticularly with alkylating agents. Estrogen is the most effective sure, or late effects of previous cancer treatments. Patients with therapy for vasomotor symptoms related to premature meno- identified genetic mutations with an increased risk of additional pause. For women with an intact uterus, estrogen should be malignancies should have genetics counseling. Patients with combined with progestin. Estrogen replacement therapy is smoking-related head and neck cancer are prone to second head contraindicated in patients with breast and endometrial can- and neck cancers, as well as lung and esophageal cancers. cer. Risk factors for infertility relate to the dose and duration of Patients exposed to chemotherapy with alkylating agents have chemotherapy as well as patient age. Consultation with fertil- an increased risk of myelodysplastic syndromes and acute leuke- ity experts should be offered to women who desire future mia. Radiation to the neck can be associated with hypothyroid- childbearing; egg and embryo harvests may be options. ism as well as thyroid cancer years later. Women receiving Fertility evaluations can often be done on an emergency basis, radiation to the mediastinum for Hodgkin lymphoma and other so delay in the initiation of definitive cancer treatment is mini- cancers have a marked increase of breast cancer, particularly if mized. Men may consider semen cryopreservation. they were treated in adolescence and early adulthood, with the Tamoxifen, aromatase inhibitors, and ovarian suppres- increased risk beginning about 8 years after treatment. Screening sion may cause menopausal symptoms, decreased libido, and MRI, mammography, or a combination of both modalities is vaginal dryness. Men commonly experience erectile dysfunc- recommended for these patients beginning at age 25 years or tion after prostate surgery or irradiation, and androgen depri- 8 years after completing radiation therapy, whichever occurs last. vation therapy suppresses libido. Cognitive Decline e A “prescription for survivorship” provides the patient Short-term and long-term declines in cognitive function are a with recommendations regarding surveillance for can- complication after cancer therapy. It remains unclear whether cer recurrence, lifestyle modifications to reduce the risk cancer and its treatment unmasks preexisting cognitive of a second malignancy, and strategies to prevent or

Short-term and long-term declines in cognitive function are a with recommendations regarding surveillance for can- complication after cancer therapy. It remains unclear whether cer recurrence, lifestyle modifications to reduce the risk cancer and its treatment unmasks preexisting cognitive of a second malignancy, and strategies to prevent or impairment, whether the decline represents a sign of more reduce the late effects of cancer treatment. rapid aging, or whether there is a more specific neurotoxic e Various factors increase the risk of secondary malignan- effect. Behavioral therapy may be beneficial. cies in patients in remission after therapy for their pri- mary cancer. e Doxorubicin and other anthracyclines can cause irre- e Mediastinal irradiation is associated with a marked versible, dose-related cardiomyopathy; trastuzumab can increase of breast cancer beginning within 8 years of treatment; screening MRI, mammography, or a combi- also induce dose-independent cardiomyopathy that is usually reversible. nation of both modalities is recommended for women beginning at age 25 years or 8 years after completion of e Bevacizumab is associated with hypertension as well as radiation therapy, whichever occurs last. an increased risk of coronary and other vascular events. e Bone loss occurs in cancer survivors who have taken long-term glucocorticoids; in women who have under- Bibliography gone surgical, irradiation, or chemotherapy-induced Issues in Oncology

versible, dose-related cardiomyopathy; trastuzumab can increase of breast cancer beginning within 8 years of treatment; screening MRI, mammography, or a combi- also induce dose-independent cardiomyopathy that is usually reversible. nation of both modalities is recommended for women beginning at age 25 years or 8 years after completion of e Bevacizumab is associated with hypertension as well as radiation therapy, whichever occurs last. an increased risk of coronary and other vascular events. e Bone loss occurs in cancer survivors who have taken long-term glucocorticoids; in women who have under- Bibliography gone surgical, irradiation, or chemotherapy-induced Issues in Oncology premature menopause or who are taking aromatase Bach PB, Giralt SA, Saltz LB. FDA approval of tisagenlecleucel: promise and complexities ofa $475000 cancer drug. JAMA. 2017;318:1861-1862. [PMID: inhibitors for breast cancer; and in men treated for 28975266] doi:10.1001/jama.2017.15218 prostate cancer with androgen deprivation therapy. Burris HA, Saltz LB, Yu PP. Assessing the value of next-generation sequencing tests in a dynamic environment. Am Soc Clin Oncol Educ Book. e Fertility preservation options should be offered before 2018;38:139-146. [PMID: 30231307] doi:10.1200/EDBK_200825 cancer treatment in patients who desire future child- June CH, O’Connor RS, Kawalekar OU, et al. CAR T cell immunotherapy for bearing. human cancer. Science. 2018;359:1361-1365. [PMID: 29567707] doi:10.1126/ science.aar6711 47