Table 1. Boxed Warnings, Common Toxicities, and Monitoring for Renal Cell Carcinoma Drugs |
Boxed warning |
Most common adverse events |
Monitoring |
VEGF inhibitors |
Axitinib9
|
None
|
Diarrhea, hypertension, fatigue, decreased appetite, nausea, dysphoria, hand-foot syndrome, weight loss, vomiting, asthenia, and constipation
|
Monitor for hypertension and manage with standard therapy. Monitor for symptoms of thromboembolism and bleeding. Monitor for signs of GI perforation or fistula periodically. Monitor thyroid function periodically. Monitor urine protein and liver enzymes periodically.
|
Cabozantinib10
|
GI perforation and fistulas; hemorrhage
|
Diarrhea, stomatitis, hand-foot syndrome, weight loss, decreased appetite, nausea, fatigue, oral pain, hair color changes, dysgeusia, hypertension, abdominal pain,
constipation, increase in liver function tests, increase in alkaline phosphatase, lymphopenia, neutropenia, thrombocytopenia, hypophosphatemia, and hypocalcemia
|
Monitor for signs of GI perforation or fistula periodically. Monitor for hypertension and manage with standard therapy. Monitor for symptoms of thromboembolism and bleeding. Monitor urine protein. Perform an oral exam and advise patients to maintain good oral hygiene to prevent osteonecrosis of the jaw.
|
Pazopanib12
|
Hepatotoxicity
|
Diarrhea, hypertension, hair color changes (depigmentation), nausea, anorexia, and vomiting
|
Monitor liver tests at weeks 3, 5, 7, and 9, then at month 3 and the end of month 4. Monitor EKG at baseline and periodically. Monitor for signs and symptoms of congestive heart failure (consider LVEF monitoring in high-risk patients). Monitor for symptoms of thromboembolism and bleeding. Monitor for signs of GI perforation or fistula periodically. Monitor thyroid function periodically. Monitor for hypertension and manage with standard therapy. Monitor urine protein periodically. Monitor for signs of infection.
|
Sunitinib11
|
Hepatotoxicity
|
Fatigue/asthenia, diarrhea, mucositis/stomatitis, nausea, decreased appetite/anorexia, vomiting, abdominal pain, hand-foot syndrome, hypertension, bleeding, dysgeusia/altered taste, dyspepsia, and thrombocytopenia
|
Monitor liver tests at baseline and with each cycle. Monitor EKG at baseline and periodically for those at risk. Monitor for signs and symptoms of congestive heart failure (consider LVEF monitoring in high-risk patients). Monitor for symptoms of thrombotic microangiopathy and bleeding. Monitor for signs of GI perforation or fistula periodically. Monitor thyroid function periodically. Monitor for hypertension and manage with standard therapy. Monitor urine protein periodically. Monitor glucose regularly for hypoglycemia. Consider an oral exam and preventive dentistry to prevent osteonecrosis of the jaw (particularly with bisphosphonates).
|
Immune checkpoint inhibitors |
Avelumab (PD-L1i)13
|
None
|
Fatigue, infusion-related reaction, musculoskeletal pain, nausea, decreased appetite, and urinary tract infection
|
Monitor for signs and symptoms of pneumonitis. Monitor liver tests at baseline and periodically for hepatitis. Monitor for signs of diarrhea. Monitor for signs of adrenal insufficiency. Monitor for changes in thyroid function. Monitor glucose for diabetes and serum creatinine for nephritis.
|
Ipilimumab (CTLA-4i)14
|
Immune-mediated adverse events
|
Fatigue, rash, diarrhea, nausea, pyrexia, musculoskeletal pain, pruritus, abdominal pain, vomiting, cough, arthralgia, decreased appetite, and dyspnea (in combination with nivolumab)
|
Monitor for signs of enterocolitis (e.g., diarrhea, abdominal pain). Monitor liver function tests before each dose. Monitor for signs and symptoms of rash and pruritus. Monitor for signs of neuropathy. Monitor for hypophysitis and adrenal insufficiency, including thyroid function. Monitor for symptoms of pneumonitis.
|
Nivolumab (PD1i)15
|
None
|
Fatigue, rash, diarrhea, nausea, pyrexia, musculoskeletal pain, pruritus, abdominal pain, vomiting, cough, arthralgia, decreased appetite, dyspnea, and upper respiratory infection (in combination with ipilimumab)
|
Monitor for symptoms of pneumonitis. Monitor for signs of colitis (e.g., diarrhea). Monitor liver function tests at baseline and periodically. Monitor for hypophysitis and adrenal insufficiency, including thyroid function. Monitor serum creatinine for nephritis. Monitor for signs and symptoms of rash. Monitor for signs of encephalitis.
|
Pembrolizumab (PD1i)16
|
None
|
Fatigue, musculoskeletal pain, decreased appetite, pruritus, diarrhea, nausea, rash, pyrexia, cough, dyspnea, constipation, pain, and abdominal pain
|
Monitor for symptoms of pneumonitis. Monitor for signs of colitis (e.g., diarrhea). Monitor liver function tests at baseline and periodically. Monitor for hypophysitis, including hypopituitarism and adrenal insufficiency. Monitor for changes in thyroid function. Monitor blood glucose for diabetes. Monitor serum creatinine for nephritis. Monitor for signs and symptoms of rash.
|
CTLA-4i, cytotoxic T-lymphocyte-associated protein 4 inhibitor; EKG, electrocardiogram; GI, gastrointestinal; LVEF, left ventricular ejection fraction; PD1i, programmed cell death protein 1 inhibitor; PD-L1i, programmed death-ligand 1 inhibitor; VEGF, vascular endothelial growth factor. |