| Drug |
Dosage |
Remarks |
| Monoclonal Antibodies |
| Bevacizumab |
In combination with Interferon α-2a for first-line treatment of advanced and/or metastatic renal cell cancer:
10 mg/kg/body wt via IV infusion given once every 2 weeks |
Adverse Reactions
- Hematologic effects (leukopenia, thrombocytopenia, neutropenia, anemia, post-op bleeding, tumor-associated hemorrhage); CNS effects (headache, peripheral sensory neuropathy, asthenia, fatigue); GI effects (stomatitis, nausea/vomiting, intra-abdominal inflammation, pain, ulcer, tumor, necrosis, diverticulitis or chemotherapy-associated colitis); Ophthalmologic effect (eye disorders); CV effects (arterial thromboembolism, venous thromboembolism [VTE], hypertension)
Special Instructions
- Initial dose should be given over 90-minutes IV infusion; second dose over 60-minutes infusion and all subsequent doses over 30-minutes infusion if well tolerated
- Avoid use in patients with recent pulmonary hemorrhage or hemoptysis
- Use with caution in patients with GI perforations, hemorrhage, hypertension, reversible posterior leukoencephalopathy syndrome, neutropenia, wound healing complications, proteinuria, arterial and venous thromboembolism, fistulae, congestive heart failure or cardiomyopathy, congenital bleeding diathesis, acquired coagulopathy or in patients receiving full dose of anticoagulants, renal and hepatic impairment
- Discontinue use in patients with tracheoesophageal fistula or any grade 4 fistula, GI perforation, hypertensive crisis or encephalopathy, medically significant hypertension, intracranial grade 3 or 4 bleeding, arterial and venous thromboembolism, necrotizing fasciitis, nephrotic syndrome
|
| Nivolumab |
3 mg/kg IV infusion over 60 minutes every 2 weeks until disease progression or unacceptable toxicity
|
Adverse Reactions
- GI effects (colitis, abdominal pain, constipation, nausea, diarrhea, stomatitis, decreased appetite); Respiratory effects (cough, dyspnea, pneumonitis); Metabolic effects (hyponatremia, increased ALT, AST, amylase, alkaline phosphatase, lipase, and creatinine, hyperglycemia, altered electrolytes); CNS effects (peripheral neuropathy, headache, dizziness, fatigue); Dermatologic effects (pruritus, rash, dry skin, alopecia, erythema); Other effects (musculoskeletal pain, pyrexia, hypothyroidism, hyperthyroidism, hypertension, edema, decreased weight, blood dyscrasias)
Special Instructions
- Do not administer as IV push or bolus injection
- Use with caution in patients with moderate or severe hepatic impairment
- Monitor liver enzymes, serum creatinine and thyroid function
|
| Pembrolizumab |
Monotherapy:
200 mg IV infusion over 30 minutes every 3 weeks or
400 mg over 30 minutes IV every 6 weeks
In combination with Axitinib or Lenvatinib:
200 mg IV infusion over 30 minutes every 3 weeks or
400 mg IV over 30 minutes every 6 weeks |
Adverse Reactions
- GI effects (diarrhea, nausea, stomatitis, mucosal inflammation, constipation); Respiratory effects (dysphonia, cough); Dermatologic effects (palmar-plantar erythrodysesthesia [PPE] syndrome, rash); Other effects (hypertension, fatigue, asthenia, hypothyroidism, decreased appetite, hepatotoxicity)
Special Instructions
- Use with caution in patients with hypothyroidism, type 1 DM, immune-mediated pneumonitis/colitis/hepatitis/nephritis/endocrinopathies/skin adverse reactions, renal failure
- Withhold treatment if any of the following occurs: Grade 2 pneumonitis, grade 2 or 3 colitis, symptomatic hypophysitis, grade 2 nephritis, grade 3 hyperthyroidism, AST or ALT >3-5x ULN or total bilirubin >1.5-3x ULN, or any other severe or grade 3 treatment-related adverse reaction
- Discontinue if life-threatening adverse events occur: Grade 3 or 4 pneumonitis, grade 3 or 4 nephritis, AST or ALT >5x ULN or total bilirubin >3x ULN, grade 3 or 4 infusion-related reactions, inability to reduce corticosteroid dose to ≤10 mg of Prednisone or equivalent per day within 12 weeks, persistent grade 2 or 3 adverse reactions (excluding endocrinopathies controlled with hormone replacement therapy) that do not recover to grade 0-1 within 12 weeks after last dose, or any severe or grade 3 treatment-related adverse reaction that recurs
|
| Protein Kinase Inhibitors |
| Axitinib |
Initial dose: 5 mg PO 12 hourly
May increase to 7 mg PO 12 hourly or 10 mg PO 12 hourly when patients have no adverse reactions >grade 2, normotensive and are not receiving antihypertensive medication for at least 2 consecutive weeks on treatment
Max dose:
10 mg PO 12 hourly
May decrease dose to 2-3 mg PO 12 hourly
|
Adverse Reactions
- CNS effects (headache, fatigue, asthenia); Respiratory effects (dyspnea, cough, dysphonia); GI effects (mucosal inflammation, decreased appetite, nausea/vomiting, diarrhea, abdominal pain, stomatitis, constipation, dyspepsia, dysgeusia); Dermatologic effects (hand-foot syndrome, rash, dry skin); CV effect (hypertension); Other effects (hypothyroidism, hemorrhage, arthralgia, proteinuria, decreased weight)
Special Instructions
- Use with caution in patients who are at risk or with a history of arterial (including transient ischemic attack, cerebrovascular accident, MI and retinal artery occlusion) or venous (including deep vein thrombosis, retinal vein occlusion or thrombosis) thromboembolic events and in patients with moderate or severe hepatic impairment
- Monitor the thyroid function, hemoglobin and hematocrit
- Discontinue treatment at least 24 hours prior to scheduled surgery and if reversible posterior leukoencephalopathy syndrome (RPLS) occurs
|
| Cabozantinib |
Monotherapy:
60 mg PO 24 hourly
May reduce to 40 mg PO 24 hourly, then to 20 mg PO 24 hourly if necessary
In combination with Nivolumab: 40 mg PO 24 hourly
May reduce dose to 20 mg PO 24 hourly, then to 20 mg PO every other day
|
Adverse Reactions
- CNS effects (headache, dizziness, asthenia); GI effects (dysgeusia, diarrhea, nausea/vomiting, stomatitis, constipation, abdominal pain, dyspepsia); Respiratory effects (dysphonia, dyspnea, cough, pulmonary embolism); Dermatologic effects (alopecia, pruritus, PPE syndrome, rash, dry skin); Musculoskeletal effects (pain in extremity, muscle spasms, arthralgia); Metabolic effects (hypophosphatemia, hypoalbuminemia, hypomagnesemia, hyponatremia, hypokalemia, hyperkalemia, hypocalcemia, hyperbilirubinemia); Other effects (anemia, hypothyroidism, decreased appetite, hypertension, proteinuria, fatigue, mucosal inflammation)
Special Instructions
- Avoid use in patients with severe hepatic or renal impairment
- Use with caution in patients who are at increased risk of GI perforations and fistulas, venous and arterial thromboembolism, severe hemorrhage, wound complications, hypertension, PPE syndrome, proteinuria and RPLS
- Use with caution in patients with history of QT interval prolongation, relevant pre-existing cardiac disease, bradycardia, electrolyte disturbances or patients taking antiarrhythmics, rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption, mild-moderate hepatic and renal impairment
- Evaluate the patient closely during the first 8 weeks of treatment to determine if dose modifications are warranted
|
| Everolimus |
10 mg PO 24 hourly |
Adverse Reactions
- CNS effects (headache, asthenia, fatigue); GI effects (anorexia, stomatitis, diarrhea, nausea/vomiting, mucosal inflammation, dysgeusia); Respiratory effects (cough, dyspnea, epistaxis, pneumonitis); Dermatologic effects (rash, pruritus, dry skin); Musculoskeletal effects (peripheral edema, pain in extremity); Hematologic effects (anemia, thrombocytopenia, neutropenia, leukopenia, lymphopenia); Metabolic effects (hypertriglyceridemia, hypophosphatemia, hyperlipidemia, hypokalemia, hypocalcemia); Other effects (infections, diabetes mellitus [DM], dehydration)
Special Instructions
- Use with caution in patients who are at increased risk of infections, elderly and with hepatic impairment
- Monitor renal function, blood glucose, lipid profile and CBC
- Patients are advised to avoid administration of live vaccine
|
| Lenvatinib mesilate |
In combination with Everolimus for advanced renal cell carcinoma following 1 prior vascular endothelial growth factor-targeted therapy:
18 mg PO 24 hourly
In combination with Pembrolizumab:
20 mg PO 24 hourly
|
Adverse Reactions
- CNS effects (insomnia, headache, dizziness); CV effects (hypotension, hypertension, hemorrhage, cardiac failure, myocardial infarction [MI], prolonged ECG QT, decreased ejection fraction); GI effects (diarrhea, abdominal pain, nausea/vomiting, oral inflammation and pain, constipation, dyspepsia, dry mouth, abnormal hepatic function); Dermatologic effects (rash, hyperkeratosis, PPE syndrome, alopecia); Musculoskeletal effects (pain, back pain, arthralgia, myalgia, extremity pain); Metabolic effects (hypocalcemia, hypomagnesemia, hypokalemia, hypercholesterolemia, increased lipase and amylase, aspartate aminotransferase, alanine aminotransferase and blood alkaline phosphatase, γ-glutamyl transferase, blood bilirubin, blood creatinine, blood urea, hypoalbuminemia); Hematologic effects (thrombocytopenia, leukopenia, neutropenia, lymphopenia); Other effects (malaise, decreased weight and appetite, UTI, hypothyroidism)
Special Instructions
- Use with caution in patients with arterial thromboembolic event within the previous 6 months, posterior reversible encephalopathy syndrome/RPLS
- Not recommended in patients with end-stage renal disease
- Monitor BP after 1 week of treatment then every 2 weeks for the first 2 months and monthly thereafter
- Monitor urine protein, ECG, electrolytes, TSH levels regularly
- Monitor for clinical symptoms or signs of cardiac decompensation
- Monitor LFTs before initiation of treatment, then every 2 weeks for the first 2 months and monthly thereafter during treatment
|
| Pazopanib HCl |
800 mg PO 24 hourly |
Adverse Reactions
- Hematologic effects (thrombocytopenia, neutropenia); Metabolic effects (anorexia, weight loss); CNS effects (headache, dizziness, tumor pain, fatigue, asthenia); CV effects (MI, QT prolongation, hypertension, asymptomatic bradycardia, chest pain, transient ischemic attack); Renal effect (proteinuria); GI effects (diarrhea, nausea/vomiting, abdominal pain, dyspepsia, lipase elevation, dysgeusia); Hepatic effects (increased ALT/AST, abnormal hepatic function, hyperbilirubinemia); Dermatologic effects (hair depigmentation, rash, alopecia, skin depigmentation, PPE syndrome); Other effect (hypothyroidism)
Special Instructions
- Avoid use in patients with severe hepatic or renal impairment or undergoing peritoneal dialysis or hemodialysis
- Discontinue use if ALT elevations >3x ULN recur or if ALT elevations >3x ULN occur concurrently with bilirubin elevations >2x ULN, hypertensive crisis, posterior reversible encephalopathy syndrome/RPLS and thrombotic microangiopathy, wound dehiscence, nephrotic syndrome occurs
- Use with caution in patients with hypertension, cardiac dysfunction (eg CHF and decreased left ventricular ejection fraction [LVEF]), QT prolongation and torsade de pointes, increased risk of thrombotic events, hemorrhage, GI perforation or fistula, infections, mild-moderate hepatic and renal impairment
- Monitor serum liver tests before initiating therapy and at week 3, 5, 7 and 9. Thereafter, monitor at month 3 and at month 4, and as clinically indicated
- Monitor thyroid function tests
|
| Sorafenib |
400 mg PO 12 hourly
May reduce dose to 400 mg PO 24 hourly
|
Adverse Reactions
- CV effects (MI, hypertension, hypertensive crisis); GI effects (abdominal pain, diarrhea, nausea/vomiting, constipation); Dermatologic effects (dry skin, erythema, pruritus, PPE syndrome, alopecia, rash); Other effects (lymphopenia, anorexia, hypophosphatemia, fatigue, GI, respiratory tract and cerebral hemorrhage, arthralgia, decreased weight, increased amylase and lipase, headache, fever)
Special Instructions
- Use with caution in patients with known dermatological toxicities, hypertension, hemorrhage, cardiac ischemia, MI, QT interval prolongation, GI perforation, on Warfarin therapy and severe hepatic impairment
- Monitor fluid and electrolyte balance in patients at risk of renal dysfunction
|
| Sunitinib |
50 mg PO 24 hourly taken daily for 4 consecutive weeks, followed by a 2-week off period (schedule 4/2) to comprise a complete cycle of 6 weeks
Dose modification of 12.5 mg increment or decrement based on individual safety and tolerability
|
Adverse Reactions
- CNS effects (dizziness, asthenia, fatigue); Dermatologic effects (skin discoloration, rash, PPE syndrome, dry skin, hair color changes, alopecia); GI effects (anorexia, GI disorders, mucosal inflammation, flatulence, dysgeusia, anorexia); Other effects (hypertension, neutropenia, dehydration)
Special Instructions
- Use with caution in patients with known severe hepatotoxicity, left ventricular dysfunction, QT interval prolongation, torsade de pointes, hypertension, hemorrhagic events including pulmonary hemorrhage, osteonecrosis of the jaw, tumor lysis syndrome, thyroid dysfunction, impaired wound healing, adrenal insufficiency
- Perform CBC with platelet count and serum chemistries including phosphate at the beginning of each treatment cycle
- Baseline periodic monitoring of LFTs, LVEF and clinical signs and symptoms of CHF
|
| Temsirolimus |
25 mg via IV infusion over a 30–60-minute period once weekly
IV Premed:
Diphenhydramine 25-50 mg IV given approximately 30 minutes before start of each dose
|
Adverse Reactions
- Hematologic effects (anemia, thrombocytopenia, neutropenia, leukopenia, lymphopenia); Metabolic effects (hypokalemia, hypertriglyceridemia, hypercholesterolemia, hyperglycemia, hyperlipidemia, hypophosphatemia); CV effects (hypertension, VTE, thrombophlebitis); Respiratory effects (rhinitis, upper respiratory tract infection, pneumonia, dyspnea, cough, epistaxis, pleural effusion, interstitial lung disease); GI effects (mucosal inflammation, pharyngitis, ageusia, dysgeusia, nausea/vomiting, diarrhea, constipation, abdominal pain, GI hemorrhage, stomatitis, gingivitis); Dermatologic effects (rash, dry skin, acne, dermatitis, ecchymosis, petechiae); Musculoskeletal effects (back pain, arthralgia, myalgia, asthenia); Renal effects (renal failure, angioneurotic edema-type, increased blood creatinine); CNS effects (insomnia, depression); GU effect (UTI); Other effects (bacterial and viral infections, pyrexia, sepsis, AST and ALT reactions with concomitant ACE inhibitors, chills, conjunctivitis, edema, pain)
Special Instructions
- Contraindicated in patients with bilirubin >1.5 x ULN
- Use with caution in patients with hyperglycemia or glucose intolerance, immunosuppression, opportunistic infections (eg Pneumocystis jirovecii pneumonia), nonspecific interstitial pneumonitis, hyperlipidemia, bowel perforation, abnormal wound healing, intracerebral bleeding with CNS tumors and/or anticoagulation therapy, thrombocytopenia, neutropenia and concurrent vaccination, renal and hepatic impairment
|
| Tivozanib |
1,340 mcg PO 24 hourly x 21 days, followed by a 7-day rest period to comprise a complete cycle of 4 weeks |
Adverse Reactions
- CV effects (hypertension, MI, angina pectoris, hemorrhage, arterial thromboembolism, VTE, flushing, persistent severe hypertension); GI effects (diarrhea, nausea/vomiting, abdominal pain, stomatitis, pancreatitis, dysphagia, GERD, abdominal distention, glossitis, gingivitis, dry mouth, dyspepsia, constipation, flatulence, dysgeusia, anorexia); Respiratory effects (dysphonia, dyspnea, cough, epistaxis, rhinorrhea, nasal congestion); CNS effects (headache, insomnia, peripheral neuropathy, dizziness, asthenia, fatigue); Metabolic effects (hypothyroidism, increased ALT/AST, blood alkaline phosphatase, and γ-glutamyl transferase); Dermatologic effects (alopecia, PPE syndrome/hand foot skin reaction, skin exfoliation, erythema, pruritus, rash, acne, dry skin); Renal effects (proteinuria, increased blood creatinine); Musculoskeletal effects (back pain, arthralgia, myalgia, chest pain); Other effects (anemia, pain, decreased appetite, vision impairment, vertigo, tinnitus, chills, pyrexia, peripheral edema)
Special Instructions
- Avoid use in patients with severe hepatic impairment
- Use with caution in patients with hypertension, malignant disease, DM, smoking, hypercholesterolemia, prior thromboembolic disease, major surgery, multiple trauma, prior VTEs, advanced age, obesity, cardiac or respiratory failure, prolonged immobility, posterior reversible encephalopathy syndrome, risk or history of bleeding, history of QT interval prolongation or other relevant pre-existing cardiac disease, risk for GI perforation or fistula, hypothyroidism, severe renal impairment and mild-moderate hepatic impairment
- Monitor for signs/symptoms of cardiac failure, proteinuria, elevations of ALT, AST and bilirubin levels before initiation and periodically throughout treatment
|
