Usual Adult Dose for Gastric Cancer

AS A SINGLE AGENT OR IN COMBINATION WITH WEEKLY PACLITAXEL:
8 mg/kg IV over 60 minutes every 2 weeks until disease progression or unacceptable toxicity
NOTE: If the first infusion is tolerated, all subsequent infusions may be administered over 30 minutes.

Comments:

• When given in combination, this drug should be administered prior to paclitaxel.
• Refer to the prescribing information for paclitaxel for dosage information.
• Premedicate patients with an IV a H1 antagonist (e.g., diphenhydramine).
• Patients who have developed a Grade 1 or 2 infusion reaction should be premedicated with histamine-1 receptor antagonist or dexamethasone (or equivalent) and acetaminophen prior to each infusion.

Use: As a single agent, or in combination with paclitaxel, for the treatment of advanced or metastatic, gastric or gastroesophageal junction (GEJ) adenocarcinoma with disease progression on or after prior fluoropyrimidine- or platinum-containing chemotherapy

Usual Adult Dose for Non-Small Cell Lung Cancer

EGFR EXON 19 DELETIONS OR EXON 21 (L858R) SUBSTITUTION MUTATIONS IN COMBINATION WITH ERLOTINIB:
10 mg/kg IV over 60 minutes every 2 weeks until disease progression or unacceptable toxicity
NOTE: If the first infusion is tolerated, all subsequent infusions may be administered over 30 minutes.

DISEASE PROGRESSION ON OR AFTER PLATINUM-BASED CHEMOTHERAPY IN COMBINATION WITH DOCETAXEL:
10 mg/kg IV over 60 minutes on Day 1 of a 21-day cycle prior to docetaxel infusion until disease progression or unacceptable toxicity
NOTE: If the first infusion is tolerated, all subsequent infusions may be administered over 30 minutes.

Comments:

• Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving this drug.
• Refer to the prescribing information for erlotinib or docetaxel for dosage information.
• Premedicate patients with an IV a H1 antagonist (e.g., diphenhydramine).
• Patients who have developed a Grade 1 or 2 infusion reaction should be premedicated with histamine-1 receptor antagonist or dexamethasone (or equivalent) and acetaminophen prior to each infusion.

Uses:

• In combination with erlotinib for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R)

substitution mutations

• In combination with docetaxel, for the treatment metastatic non-small cell lung cancer (NSCLC) with disease progression on or after platinum-based chemotherapy (patients with epidermal growth factor receptor [EGFR] or anaplastic lymphoma kinase (ALK) genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving this drug)

Usual Adult Dose for Colorectal Cancer

8 mg/kg IV over 60 minutes every 2 weeks until disease progression or unacceptable toxicity
NOTE: If the first infusion is tolerated, all subsequent infusions may be administered over 30 minutes.

Comments:

• Administer this drug prior to administration of FOLFIRI.
• Refer to the prescribing information for fluorouracil, leucovorin, and irinotecan for dosage information.
• Premedicate patients with an IV a H1 antagonist (e.g., diphenhydramine).
• Patients who have developed a Grade 1 or 2 infusion reaction should be premedicated with histamine-1 receptor antagonist or dexamethasone (or equivalent) and acetaminophen prior to each infusion.

Use: In combination with FOLFIRI (irinotecan, folinic acid, and 5-fluorouracil) for the treatment of metastatic colorectal cancer (mCRC) with disease progression on or after prior therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine

Usual Adult Dose for Hepatocellular Carcinoma

8 mg/kg IV over 60 minutes every 2 weeks until disease progression or unacceptable toxicity
NOTE: If the first infusion is tolerated, all subsequent infusions may be administered over 30 minutes.

Comments:

• Premedicate patients with an IV a H1 antagonist (e.g., diphenhydramine).
• Patients who have developed a Grade 1 or 2 infusion reaction should be premedicated with histamine-1 receptor antagonist or dexamethasone (or equivalent) and acetaminophen prior to each infusion.

Use: As a single agent for the treatment of patients with hepatocellular carcinoma (HCC) who have an alpha fetoprotein (AFP) of 400 ng/mL or greater and have been treated with sorafenib

Renal Dose Adjustments

No adjustment recommended.

Liver Dose Adjustments

• Mild (total bilirubin within ULN and aspartate aminotransferase [AST] greater than ULN or total bilirubin greater than 1 to 1.5 times ULN and any AST) or moderate (total bilirubin greater than 1.5 to 3 x ULN and any AST) hepatic impairment: No adjustment recommended.
• Severe renal impairment: Data not available
• Clinical deterioration was reported in patients with Child-Pugh B or C cirrhosis who received this drug as a single agent.

Dose Adjustments

MANUFACTURER RECOMMENDED DOSE MODIFICATIONS:
HEMORRHAGE:

• Grade 3 or 4: Permanently discontinue therapy.

GI PERFORATION:

• All Grades: Permanently discontinue therapy.

WOUND HEALING COMPLICATIONS:

• All Grades: Withhold therapy for 28 days prior to elective surgery; resume therapy no sooner than 28 days after surgery and the wound is fully healed; discontinue therapy for wound healing complications that require medical intervention.

ARTERIAL THROMBOEMBOLIC EVENTS:

• All Grades: Permanently discontinue therapy.

HYPERTENSION:

• Severe hypertension: Withhold therapy until controlled.
• Severe hypertension not controlled with antihypertensives: Permanently discontinue therapy.

INFUSION RELATED REACTIONS (IRRs):

• Grade 1 or 2 IRRs: Reduce the infusion rate by 50%.
• Grade 3 or 4 IRRs: Permanently discontinue therapy.

PROTEINURIA:

• First occurrence of increased urine protein levels greater than or equal to 2 g per 24 hours: Withhold therapy until urine protein level is less than 2 g per 24 hours; resume therapy at a reduced dose: Reduce 8 mg dose to 6 mg; reduce 10 mg dose to 8 mg.
• Reoccurrence of urine protein level greater than 2 g per 24 hours following initial dose reduction: Withhold therapy until urine protein level is less than 2 g per 24 hours; resume therapy at a reduced dose: Reduce 6 mg dose to 5 mg; reduce 8 mg dose to 6 mg.
• Urine protein level greater than 3 g per 24 hours or in the setting of nephrotic syndrome: Permanently discontinue therapy.

Precautions

CONTRAINDICATIONS:

• None

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• Therapy should be initiated and supervised by physicians experienced in oncology.
• Do not administer this drug as an IV push or bolus.
• Gently invert the container for adequate mixing.
• Do not dilute with other solutions or co-infuse with other electrolytes or drugs.
• Administer drug via infusion pump over 60 minutes through a separate infusion line.
• Flush the line with sterile sodium chloride (0.9%) solution for injection at the end of the infusion.
• Therapy should be temporarily discontinued if severe hypertension develops.
• Continue use until disease progression or unacceptable toxicity.

Storage requirements:

• Store in a refrigerator at 2C to 8C (36F to 46F)
• Do not freeze the vial.
• The reconstituted solution is stable for 24 hours under refrigeration 2C to 8C (36F to 46F) and for 4 hours at room temperature (below 25C or 77F).

Reconstitution/preparation techniques:

• Sodium chloride 0.9% is the only diluent that should be used for reconstitution. Dextrose solutions should not be used.
• Refer to the manufacturer product information.

General:

• Protect from light
• Do not shake the vial.
• Discard the vial if matter or discolorations are present.

Patient advice:

• This drug can cause severe bleeding. Contact your healthcare provider if you are bleeding or have symptoms of bleeding (including lightheadedness).
• Your blood pressure should be monitored every 2 weeks or more frequently.
• You should notify your healthcare provider if you experience severe diarrhea, vomiting, or severe abdominal pain.
• This drug can delay wound healing. Discuss any surgical procedures with your healthcare provider.
• Avoid getting pregnant during treatment with this drug and for at least 3 months following your last dose.
• Do not nurse a baby while being treated with this drug.