| Drug |
Dosage |
Remarks |
| Monoclonal Antibodies |
| Atezolizumab |
In combination with Bevacizumab:
840 mg IV infusion every 2 weeks or 1,200 mg IV infusion every 3 weeks or 1,680 mg IV infusion every 4 weeks until loss of clinical benefit or unmanageable toxicity
Bevacizumab 15 mg/kg IV infusion every 3 weeks before Atezolizumab when given on the same day |
Adverse Reactions
- GI effects (nausea, diarrhea, decreased appetite); Hematologic effects (anemia, thrombocytopenia); Other effects (fatigue, rash, cough, alopecia, peripheral neuropathy)
Special Instructions
- Use with caution in patients with hepatitis, thyroid disorders, adrenal insufficiency, myasthenia gravis, severe renal or hepatic impairment
- Monitor liver, renal and thyroid function before and during treatment
- May continue Atezolizumab monotherapy if Bevacizumab is discontinued due to unacceptable toxicity
|
Bevacizumab
|
In combination with Atezolizumab: 15 mg/kg IV infusion every 3 weeks after administration of Atezolizumab |
Adverse Reactions
- CV effects (hypertension, arterial thromboembolism); Hematologic effects (hemorrhage, neutropenia, leukopenia); CNS effects (reversible posterior leukoencephalopathy syndrome, pain, headache); Dermatologic effects (alopecia, exfoliative dermatitis); GI effects (GI perforation, hemorrhage, nausea/vomiting, constipation, diarrhea); Other effects (infection, proteinuria, hypokalemia)
Special Instructions
- Use with caution in patients with hypertension; monitor blood pressure (BP) closely
- Should not be given within 28 days of major surgery and only after complete healing of incision
- Discontinue 28 days prior to elective surgery, in patients with nephrotic syndrome and with arterial thromboembolic events
|
| Dostarlimab |
500 mg IV infusion over 30 minutes every 3 weeks x 4 cycles followed by 1,000 mg every 6 weeks until disease progression or unacceptable toxicity |
Adverse Reactions
- GI effects (nausea/vomiting, diarrhea, colitis, pancreatitis); Hematologic effects (anemia, decreased lymphocytes); Metabolic effects (decreased sodium, increased alkaline phosphatase, decreased albumin, increased transaminases, hypothyroidism); Musculoskeletal effects (arthralgia, myalgia); Other effects (pneumonitis, fatigue, asthenia, rash, pruritus, pyrexia, chills)
Special Instructions
- Use with caution in patients with history of allogeneic hematopoietic stem cell transplantation
- Monitor for signs and symptoms of immune-mediated adverse reactions (pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, rash, arthralgia)
- Evaluate clinical chemistries, including liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment
|
| Durvalumab |
Adult ≤30 kg: 20 mg/kg IV infusion 1 hour after Tremelimumab on day 1
Continue 20 mg/kg IV as monotherapy every 4 weeks until disease progression or unacceptable toxicity
Adult >30 kg: 1,500 mg IV infusion 1 hour after Tremelimumab on day 1
Continue 1,500 mg IV as monotherapy every 4 weeks until disease progression or unacceptable toxicity |
Adverse Reactions
- GI effects (hepatitis, colitis); Other effects (pneumonitis, fatigue, asthenia, rash, other immune-mediated allergic reactions, infusion-related reactions
Special Instructions
- Observe for signs and symptoms of infusion reaction to Tremelimumab for 60 minutes prior to administration
- Monitor for signs and symptoms of immune-mediated adverse reactions (pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, rash, arthralgia)
- Evaluate clinical chemistries, including liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment
|
| Nivolumab |
240 mg IV infusion over 30 minutes every 2 weeks or
480 mg IV infusion over 30 minutes 4 weekly until disease progression or unacceptable toxicity
In combination with Ipilimumab: 1 mg/kg IV infusion over 30 minutes every 3 weeks followed by Ipilimumab 3 mg/kg IV over 30 minutes on the same day ≥30 minutes after completion of Nivolumab infusion x 4 doses |
Adverse Reactions
- GI effects (colitis, abdominal pain, constipation, nausea); Respiratory effects (cough, dyspnea, pneumonitis, cough, dyspnea); Metabolic effects (hyponatremia, increased AST/lipase, creatinine, hyperglycemia, altered electrolytes); CNS effects (peripheral neuropathy, headache, dizziness); Dermatologic effects (pruritus, rash, dry skin, alopecia, erythema); Other effects (fatigue, musculoskeletal pain, pyrexia, hypothyroidism, hyperthyroidism, hypertension, edema, decreased appetite, decreased weight, stomatitis, 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 |
200 mg IV infusion over 30 minutes every 3 weeks or
400 mg IV infusion over 30 minutes every 6 weeks until disease progression or unacceptable toxicity |
Adverse Reactions
- GI effects (nausea, constipation, decreased appetite, diarrhea); Respiratory effects (cough, pneumonitis, dyspnea, pneumonia); Dermatologic effects (pruritus, rash, cellulitis); Other effects (fatigue, arthralgia, renal failure, pain)
Special Instructions
- Withhold treatment if any of the following occurs: Moderate pneumonitis, moderate or severe immune-mediated colitis, moderate hypophysitis, severe hyperglycemia, moderate immune-mediated nephritis
- Discontinue if life-threatening adverse events of pneumonitis, colitis, hypophysitis, hyperthyroidism, nephritis, infusion reactions, severe liver enzyme elevations occur
- Monitor liver enzymes, serum creatinine, and thyroid and renal function
|
Ramucirumab
|
8 mg/kg IV infusion over 60 minutes every 2 weeks
May reduce infusion time to 30 minutes if first infusion is tolerated |
Adverse Reactions
- Hematologic effects (neutropenia, thrombocytopenia, leukopenia); GI effects (GI hemorrhage, stomatitis, diarrhea, abdominal pain); CV effect (hypertension); Other effects (asthenia, fatigue, proteinuria, peripheral edema, palmar-plantar erythrodysesthesia [PPE], mucosal inflammation, epistaxis, hypoalbuminemia)
Special Instructions
- Discontinue use with GI perforation, fistula formation, grade 3 or 4 bleeding, severe arterial thromboembolic events, urine protein level >3 g/24 hr
- Use with caution in cases of hypertension, severe liver cirrhosis
- Monitor blood counts and coagulation parameters
- Should be temporarily suspended for at least 4 weeks prior to elective surgery
|
| Tremelimumab |
Adult ≤30-40 kg: 4 mg/kg IV on day 1 followed by Durvalumab 20 mg/kg IV
Continue Durvalumab 20 mg/kg IV as monotherapy every 4 week until disease progression or unacceptable toxicity
Adult >30-40 kg: 300 mg IV on day 1 followed by Durvalumab 1,500 mg IV
Continue Durvalumab 1,500 mg IV as monotherapy every 4 weeks until disease progression or unacceptable toxicity |
Adverse Reactions
- GI effects (abdominal pain, decreased appetite, diarrhea, nausea, increased LFTs); Dermatologic effects (pruritus, rash, dermatitis); Endocrine and metabolic effects (decreased serum albumin, calcium and sodium, hypothyroidism, increased serum glucose, potassium and creatinine); Hematologic effects (decreased hemoglobin and platelet count, leukopenia, lymphocytopenia); Other effects (fatigue, musculoskeletal pain, fever, development of neutralizing antibodies)
Special Instructions
- Observe for signs and symptoms of infusion reaction for 60 minutes prior to administering Durvalumab
- Monitor liver enzymes, serum creatinine and thyroid function at baseline and prior to each dose
- Monitor for signs/symptoms of infusion reactions
|
| Protein Kinase Inhibitors |
| Cabozantinib |
60 mg PO 24 hourly
May reduce to 40 mg PO 24 hourly, then to 20 mg PO 24 hourly if necessary |
Adverse Reactions
- CNS effects (headache, dizziness); 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, asthenia)
Special Instructions
- Should be taken on an empty stomach
- 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 reversible posterior leukoencephalopathy syndrome
- 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, hepatitis and renal impairment
- Evaluate the patient closely during the first 8 weeks of treatment to determine if dose modifications are warranted
|
| Entrectinib |
NTRK gene fusion-positive:
≥12 years old with BSA 0.91-1.10 m2:
400 mg PO 24 hourly
≥12 years old with BSA 1.11-1.50 m2:
500 mg PO 24 hourly
≥12 years old with BSA >1.50 m2:
600 mg PO 24 hourly
Adult: 600 mg PO 24 hourly |
Adverse Reactions
- GI effects (constipation, dysgeusia, diarrhea, nausea/vomiting); CNS effects (dizziness, cognitive impairment); Respiratory effects (dyspnea, cough); Musculoskeletal effects (myalgia, arthralgia); Other effects (fatigue, edema, dysesthesia, increased weight, pyrexia, vision disorders)
Special Instructions
- Use with caution in patients with new or worsening CHF, myocarditis, QT prolongation, at risk for fractures, hyperuricemia
- Withhold treatment for new onset or worsening CHF, new visual changes or changes that interfere with activities of daily living or presence of CNS effects (cognitive impairment, mood disorders, dizziness, sleep disturbances)
- Assess left ventricular ejection fraction, serum uric acid levels prior to initiation of therapy
- Monitor LFTs every 2 weeks during the first month of treatment, then monthly thereafter, and as clinically indicated
|
| Larotrectinib |
NTRK gene fusion-positive:
1 month-18 years od: 100 mg/m2 PO 12 hourly
Max dose: 100 mg/dose
Adult: 100 mg PO 12 hourly
|
Adverse Reactions
- GI effects (nausea/vomiting, constipation, diarrhea); CNS effects (delirium, dysarthria, dizziness, gait disturbance, paresthesia, memory impairment); Other effects (increased LFTs, anemia, fatigue, cough)
Special Instructions
- Swallow capsules whole with water
- Use with caution in patients with hepatic impairment, women of childbearing potential
- Withhold or permanently discontinue if with neurologic adverse reactions
|
| Lenvatinib |
<60 kg: 8 mg PO 24 hourly
≥60 kg: 12 mg PO 24 hourly |
Adverse Reactions
- CV effects (hypertension, peripheral edema); GI effects (diarrhea, decreased appetite, abdominal pain, nausea); Other effects (fatigue, arthralgia/myalgia, hemorrhagic events, weight loss, proteinuria, hypothyroidism, PPE syndrome, dysphonia)
Special Instructions
- BP should be controlled before treatment and monitored while on treatment
- Signs and symptoms of cardiac dysfunction should be monitored
|
| Regorafenib |
Patients who have been previously treated with Sorafenib: 160 mg PO 24 hourly for 3 weeks followed by 1 week off therapy to comprise a treatment cycle of 4-week period |
Adverse Reactions
- GI effects (severe liver injury, hemorrhage, GI perforation, diarrhea, decreased appetite & food intake); CV effect (hypertension); Other effects (pain, asthenia/fatigue, hand-foot skin infection, dysphonia, alopecia)
Special Instructions
- Should be taken with food; take at the same time each day with a low-fat meal
- Use with caution in patients with Gilbert's syndrome, severe hepatic impairment, KRAS mutant tumors, hypertension, hemorrhage, cardiac ischemia and/or infarction, GI perforation
- Perform LFTs before starting therapy
|
| Repotrectinib |
NTRK gene fusion-positive solid tumors:
160 mg PO 24 hourly x 14 days then increased to 160 mg PO 12 hourly until disease progression or unacceptable toxicity |
Adverse Reactions
- GI effects (nausea/vomiting, constipation, dysgeusia, diarrhea, decreased appetite); CV effect (edema); Endocrine/metabolic effects (decreased/increased serum glucose, increased serum potassium and/or sodium, weight gain); Hematologic effects (decreased neutrophils and/or hemoglobin, increased INR, prolonged prothrombin time, lymphocytopenia); Hepatic effects (increased AST, ALT and/or alkaline phosphatase); CNS effects (ataxia, cognitive dysfunction, anemia, aphasia, confusion, delirium, delusion, hallucination, impaired consciousness, dizziness, peripheral neuropathy, drowsiness, hypersomnia, insomnia, fatigue, headache); Respiratory effects (cough, dyspnea, pneumonia); Other effects (visual disturbance, myalgia)
Special Instructions
- Monitor LFTs and creatine phosphokinase every 2 weeks during the first month of therapy then monthly thereafter and as clinically indicated; monitor serum uric acid before initiation then periodically during treatment
- Monitor for signs and symptoms of CNS toxicity and new or worsening pulmonary symptoms indicative of interstitial lung disease
|
| Selpercatinib |
RET gene fusion-positive tumors
<50 kg: 120 mg PO 12 hourly
≥50 kg: 160 mg PO 12 hourly
Continue until disease progression or unacceptable toxicity |
Adverse Reactions
- CV effects (edema, hypertension, prolonged QT interval on ECG); Endocrine and metabolic effects (decreased serum albumin, calcium, glucose, magnesium and sodium, hypothyroidism, increased serum cholesterol, creatinine and potassium); GI effects (abdominal pain, constipation, diarrhea, nausea/vomiting, xerostomia); Hematologic effects (decreased hemoglobin, neutrophils and platelet count, hemorrhage, lymphocytopenia); Hepatic effects (increased serum transaminase, alkaline phosphatase and bilirubin); Respiratory effects (cough, dyspnea); Other effects (skin rash, fatigue, headache)
Special Instructions
- Confirm presence of RET gene fusion before initiation
- Avoid in patients with uncontrolled hypertension
- Permanently discontinue if severe or life-threatening hemorrhage occurs
- Withhold, reduce the dose, or permanently discontinue if hepatotoxicity or hypertension occurs
- Monitor the following:
- BP at baseline, after 1 week of treatment and monthly thereafter
- Development of new or worsening pulmonary symptoms during treatment, assess QT interval, electrolytes and TSH at baseline and periodically during treatment
- LFTs before initiation, every 2 weeks during first 3 months of treatment then monthly thereafter
|
Sorafenib
|
400 mg PO 12 hourly
Treatment should continue as long as clinical benefit is observed or until unacceptable toxicity occurs |
Adverse Reactions
- GI effects (diarrhea, anorexia, nausea, abdominal pain, drug-induced hepatitis); CV effects (hypertension/hypertensive crisis, myocardial infarction [MI]/ischemia); Other effects (fatigue, weight loss, rash/desquamation, hand-foot skin syndrome, alopecia)
Special Instructions
- Should be taken on an empty stomach; may take with a low- or moderate-fat meal
- Use with caution in patients with dermatological toxicities, hypertension, hemorrhage, cardiac ischemia and/or infarction, wound healing complications, GI perforation, hepatic and renal impairment
- Monitor BP regularly
|
