Usual Adult Dose for Ovarian Cancer

Usual dose: 6 mg/kg adjusted ideal body weight (AIBW) as an IV infusion once every 3 weeks

Duration of therapy: Until disease progression or unacceptable toxicity

Comments:

• This indication is granted accelerated approval based on tumor response rate and durability of response. Continued approval of this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
• Confirm the presence of folate receptor alpha tumor expression prior to initiation of treatment.
• Information regarding FDA-approved tests for folate receptor alpha tumor is available at http://www.fda.gov/CompanionDiagnostics.
• Refer to manufacturer product information for AIBW calculation.
• Administer premedications (corticosteroid, antihistamine, antipyretic, antiemetic) before each infusion of this drug to reduce the incidence of severity of infusion related reactions (IRRs), nausea, and vomiting.
• Refer to manufacturer product labeling for more information on dosing of premedications.

Use: Patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer with folate receptor alpha positive tumor expression who have previously received one to three lines of systemic treatments.

Usual Adult Dose for Fallopian Tube Cancer

Usual dose: 6 mg/kg adjusted ideal body weight (AIBW) as an IV infusion once every 3 weeks

Duration of therapy: Until disease progression or unacceptable toxicity

Comments:

• This indication is granted accelerated approval based on tumor response rate and durability of response. Continued approval of this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
• Confirm the presence of folate receptor alpha tumor expression prior to initiation of treatment.
• Information regarding FDA-approved tests for folate receptor alpha tumor is available at http://www.fda.gov/CompanionDiagnostics.
• Refer to manufacturer product information for AIBW calculation.
• Administer premedications (corticosteroid, antihistamine, antipyretic, antiemetic) before each infusion of this drug to reduce the incidence of severity of infusion related reactions (IRRs), nausea, and vomiting.
• Refer to manufacturer product labeling for more information on dosing of premedications.

Use: Patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer with folate receptor alpha positive tumor expression who have previously received one to three lines of systemic treatments.

Usual Adult Dose for Peritoneal Cancer

Usual dose: 6 mg/kg adjusted ideal body weight (AIBW) as an IV infusion once every 3 weeks

Duration of therapy: Until disease progression or unacceptable toxicity

Comments:

• This indication is granted accelerated approval based on tumor response rate and durability of response. Continued approval of this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
• Confirm the presence of folate receptor alpha tumor expression prior to initiation of treatment.
• Information regarding FDA-approved tests for folate receptor alpha tumor is available at http://www.fda.gov/CompanionDiagnostics.
• Refer to manufacturer product information for AIBW calculation.
• Administer premedications (corticosteroid, antihistamine, antipyretic, antiemetic) before each infusion of this drug to reduce the incidence of severity of infusion related reactions (IRRs), nausea, and vomiting.
• Refer to manufacturer product labeling for more information on dosing of premedications.

Use: Patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer with folate receptor alpha positive tumor expression who have previously received one to three lines of systemic treatments.

Renal Dose Adjustments

• Mild to moderate renal impairment: No adjustment recommended
• Severe renal impairment: Unknown

Liver Dose Adjustments

• Mild hepatic impairment: No adjustment recommended
• Moderate to severe hepatic impairment: Avoid administration

Dose Adjustments

DOSE REDUCTION FOR ADVERSE REACTIONS:

• Starting dose: 6 mg/kg AIBW
• First dose reduction: 5 mg/kg AIBW
• Second dose reduction: 4 mg/kg AIBW
• This drug should be discontinued permanently in patients who cannot tolerate 4 mg/kg AIBW dose.

DOSE MODIFICATIONS FOR ADVERSE REACTIONS:
Keratitis/Keratopathy:

• Nonconfluent superficial keratitis: Monitor
• Confluent superficial keratitis, a cornea epithelial defect, or 3-line or more loss in best corrected visual acuity: Withhold dose until improved or resolved, then maintain at same dose level or consider dose reduction.
• Corneal ulcer or stromal opacity or best corrected distance visual acuity 20/200 or worse: Withhold the dose until improved or resolved, then resume at one lower dose level.
• Corneal perforation: Discontinue the drug permanently.

Uveitis:

• Grade 1/Rare cell in anterior chamber: Monitor
• Grade 2/1-2+ Cell or Flare in anterior chamber: Withhold the dose until severity reduces to grade 1 or less, then maintain dose at same dose level.
• Grade 3/3+ Cell or Flare in anterior chamber: Withhold the dose until severity reduces to grade 1 or less, then resume at one lower dose level.
• Grade 4/Hypopyon: Discontinue the drug permanently.

Pneumonitis:

• Grade 1: Monitor
• Grade 2: Withhold the dose until severity reduces to grade 1 or less, then maintain the same dose or consider dose reduction by one dose level
• Grade 3 or 4: Discontinue the drug permanently.

Infusion-Related Reactions/Hypersensitivity:

• Grade 1: Maintain infusion rate
• Grade 2:
• Interrupt infusion and administer supportive treatment.
• Post recovery from symptoms, resume the infusion at 50% of the previous rate, and if no further symptoms develop, consider increasing infusion rate as appropriate until the completion.
• Administer additional premedication for future cycles.
• Grade 3 or 4:
• Immediately stop infusion and administer supportive treatment.
• Advise patient to seek emergency treatment and notify their healthcare provider, promptly, if the infusion-related symptoms reappear.
• Discontinue the drug permanently.

Other adverse reactions:

• Grade 3: Withhold dose until severity reduces to grade 1 or less, then resume at one lower dose level.
• Grade 4: Discontinue the drug permanently.

Precautions

US BOXED WARNINGS: OCULAR TOXICITY

• This drug can cause severe ocular toxicities, including visual impairment, keratopathy, dry eye, photophobia, eye pain, and uveitis.
• Ophthalmic exam including visual acuity and slit lamp exam should be conducted before initiating this treatment, every other cycle for first 8 cycles, and as required clinically.
• Prophylactic care such as artificial tears and ophthalmic topical steroids should be administered.
• In the event of ocular toxicities, interrupt the treatment until symptoms improve or resolve, then resume at the same dose or consider dose reduction.
• Permanently discontinue this drug for grade 4 ocular toxicities.

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:

• The infusion bag should be visually inspected for particulate matter and discoloration prior to administration.
• Pre-medications should be administered before administering this drug.
• For IV administration only; 0.2 or 0.22 micron polyethersulfone (PES) in-line filter should be used and must not be substituted with any other filter.
• Initial dose should be administered as an IV infusion at the rate of 1 mg/min; If well tolerated after 30 minutes, the infusion rate can be increased to 3 mg/min; If well tolerated after 30 minutes, the infusion rate can be increased to 5 mg/min.
• If patient does not experience any infusion related reactions with previous dose, the subsequent infusions can be administered at a maximum infusion rate of 5 mg/min, as tolerated.
• After infusion, the infusion line should be flushed with 5% dextrose injection, USP to ensure full delivery of dose; Other IV fluids are not compatible with this drug and must not be used for flushing.

Storage requirements:

• Refrigerate at 2C to 8C (36F to 46F) until the time of preparation in the original carton to protect from light.
• Do not freeze or shake.

Reconstitution/preparation techniques:

• This drug is hazardous. Follow appropriate handling and disposal procedures.
• Refer to manufacturer product information for reconstitution/preparation techniques.

IV compatibility:

• This drug is incompatible with 0.9% sodium chloride injection.
• This should not be mixed with any other drug or intravenous fluid.

Patient advice:

• Patients should read the FDA-approved drug product labeling.
• Patients should be informed about possible ocular toxicities and need for an eye examination before initiating and during the treatment.
• If patient experiences any ocular discomfort, immediately contact health care provider.
• Patients should take prophylactic care of eyes by using steroid eye drops and artificial tear substitutes.
• Patients should immediately report any new or worsening respiratory symptoms to their health care provider.
• Females of childbearing potential or pregnant women should be apprised of potential risk to a fetus.
• Inform heath care provider in case of known or suspected pregnancy.
• Females of childbearing potential should use an effective method of contraception during the treatment and for 7 months after the last dose.
• Women should not breastfeed during treatment and for 1 month after the last dose.