Necitumumab

Indications

Necitumumab is used for: Non-small Cell Lung Cancer Indicated for first-line treatment of metastatic squamous NSCLC in combination with gemcitabine and cisplatin

Adult Dose

Non-small Cell Lung Cancer Indicated for first-line treatment of metastatic squamous NSCLC in combination with gemcitabine and cisplatin 800 mg IV infused over 1 hr on days 1 and 8 of each 3-week cycle prior to gemcitabine and cisplatin infusion Continue therapy until disease progression or unacceptable toxicity Dosage Modifications Infusion-related reactions Grade 1: Reduce the infusion rate by 50% Grade 2: Stop the infusion until signs and symptoms have resolved to grade 0 or 1; resume infusion at 50% reduced rate for all subsequent infusions Grade 3 or 4 IRR: Permanently discontinue Also see Administration Dermatologic toxicity Grade 3 rash or acneiform rash: Withhold until symptoms resolve to grade ?2, then resume infusion at reduced dose of 400 mg for at least 1 treatment cycle; if symptoms do not worsen, may increase dose to 600 mg and 800 mg in subsequent cycles Permanently discontinue if Grade 3 rash or acneiform rash do not resolve to grade ?2 within 6 wk Reactions worsen or become intolerable at a dose of 400 mg Patient experiences grade 3 skin induration/fibrosis Grade 4 dermatologic toxicity

Child Dose

Renal Dose

Administration

IV Preparation Inspect vial contents for particulate matter and discoloration prior to dilution Discard vial if particulate matter or discoloration is identified Dilute the required dosage volume with 0.9% NaCl in an IV infusion container to a final volume of 250 mL Do not use solutions containing dextrose Do not dilute with other solutions or coinfuse with other electrolytes or medication Gently invert the container to ensure adequate mixing (do not shake) IV Administration Administer diluted solution via infusion pump over 1 hr through a separate infusion line Flush line with 0.9% NaCl at the end of the infusion Premedication For patients who have experienced a previous grade 1 or 2 infusion-related reaction (IRR), premedicate with diphenhydramine (or equivalent) prior to all subsequent necitumumab infusions For patients who have experienced a second grade 1 or 2 occurrence of IRR, premedicate for all subsequent infusions with diphenhydramine (or equivalent), acetaminophen, and dexamethasone (or equivalent) prior to each necitumumab infusion

Contra Indications

Hypersensitivity

Precautions

Cardiopulmonary arrest and/or sudden death occurred in 3% of patients treated with necitumumab in combination with gemcitabine and cisplatin Closely monitor serum electrolytes, including serum magnesium, potassium, and calcium, with aggressive replacement when warranted during and after necitumumab (administer drug through dedicated IV line; do not mix with electrolyte or dextrose solutions) Hypomagnesemia occurred in 83% of patients receiving necitumumab in combination with gemcitabine and cisplatin, and was severe in 20% of patients Monitor patients for hypomagnesemia, hypocalcemia, and hypokalemia prior to each dose during treatment and for at least 8 weeks following completion Withhold drug for grade 3 or 4 electrolyte abnormalities. Replete electrolytes as medically appropriate Discontinue if severe venous or arterial thrombosis occurs Dermatologic toxicities, including rash, dermatitis acneiform, acne, dry skin, pruritus, generalized rash, skin fissures, maculopapular rash and erythema, occurred in 79% of patients, typically within the first 2 weeks of therapy; limit sun exposure and discontinue for severe toxicity Infusion-related reactions may occur; discontinue for severe reactions Lactation Unknown if distributed in human breast milk Advise a nursing woman not to breastfeed during treatment and for 3 months following the final dose

Pregnancy-Lactation

Based on animal data and its mechanism of action, can cause fetal harm when administered during pregnancy

Interactions

Adverse Effects

Side effects of Necitumumab : >10% Hypomagnesemia (83%) Hypocalcemia (45%) Rash (44%) Hypocalcemia (albumin corrected) (36%) Hypophosphatemia (31%) Vomiting (29%) Hypokalemia (28%) Hypomagnesemia, grade 3-4 (20%) Diarrhea (16%) Dermatitis acneiform (15%) Weight decreased (13%) Stomatitis (11%) Headache (11%) 1-10% Hemoptysis (10%) Venous thromboembolic events (9%) Acne (9%) Hypophosphatemia, grade 3-4 (8%) Paronychia (7%) Conjunctivitis (7%) Pruritus (7%) Dry skin (7%) Hypocalcemia, grade 3-4 (6%) Hypokalemia, grade 3-4 (5%) Skin fissures (5%) Pulmonary embolism (5%) Venous thromboembolic events, grade 3-4 (5%) Hypocalcemia (albumin corrected), grade 3-4 (4%) Vomiting, grade 3-4 (3%) Diarrhea, grade 3-4 (2%) Stomatitis, grade 3-4 (1%)

Mechanism of Action

Epidermal growth factor receptor (EGFR) inhibitor; monoclonal antibody that binds to the human EFGR and blocks interaction between EGFR and its ligands Expression and activation of EGFR has been correlated with malignant progression, induction of angiogenesis, and inhibition of apoptosis