Drug type
▪ Human epidermal growth factor receptor type 1/epidermal growth factor receptor (HER1/EGFR) tyrosine kinase inhibitor
Indications
▪ Monotherapy for treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) after failure of at least one prior chemotherapy regimen
▪ Monotherapy for maintenance of patients with locally advanced or metastatic NSCLC whose disease has not progressed after four cycles of platinum-based first-line chemotherapy
▪ In combination with gemcitabine (Gemzar) as first-line treatment of locally advanced, unresectable, or metastatic pancreatic cancer
Unlabeled use
▪ Treatment of squamous cell head and neck cancer
Mechanism of action
▪ Mechanism of action is not entirely understood
▪ HER1 and EGFR receptors are directly involved in intercellular signaling in systems governing cell division and proliferation
—They are highly active and often overexpressed in rapidly dividing tumor cells
▪ By inhibiting the function of these receptors, erlotinib is thought to limit tumor cells' ability to divide and metastasize and may help initiate pathways of apoptotic cell death
Dosage and administration
▪ Non-small cell lung cancer
—150 mg PO daily at least 1 hour before or 2 hours after food
—Continue treatment until disease progression or unacceptable toxicity occurs
▪ Pancreatic cancer
—100 mg PO daily at least 1 hour before or 2 hours after food, in combination with gemcitabine
—Continue treatment until disease progression or unacceptable toxicity occurs
▪ Dose modifications
—When dose reduction is necessary, reduce the dose in 50-mg increments
—In patients who develop acute onset of new or progressive pulmonary symptoms (eg, cough, dyspnea, fever), interrupt treatment pending diagnostic evaluation
—If interstitial lung disease is diagnosed, discontinue erlotinib and institute appropriate treatment
—Discontinue erlotinib for hepatic failure or GI perforation
—Patients with dehydration who are at risk for renal failure, patients who develop severe skin reactions, patients who develop severe diarrhea unresponsive to loperamide or who become dehydrated, or patients with acute/worsening ocular disorders may require dose reduction or temporary interruption of therapy
▪ CYP-450 therapy
—In patients receiving a strong CYP3A4 inhibitor or an inhibitor of both CYP3A4 and CYP1A2, consider a dose reduction
—In patients receiving CYP3A4 inducers, alternative treatment lacking CYP3A4-inducing activity is strongly recommended
▪ If an alternative is unavailable, consider increasing the dose of erlotinib, as tolerated, at 2-wk intervals
▪ Reduce the erlotinib dose immediately after discontinuing the CYP3A4 inducer
▪ Cigarette smoking
—Advise patients to stop smoking
—In patients who continue to smoke, consider a cautious increase in dose of erlotinib up to 300 mg
▪ Safety and efficacy of doses higher than recommended starting dose not established in patients who continue to smoke for more than 14 days
—Reduce dose of erlotinib immediately after cessation of smoking
Pregnancy and lactation
▪ Pregnancy category D
—Erlotinib may cause fetal harm when administered to a pregnant woman
▪ Excretion in breast milk is unknown
Cautions and adverse effects
▪ Cautions
—Hepatic function: Hepatic failure and hepatorenal syndrome (including fatalities) have been reported; use with caution, especially in patients with total bili-rubin more than 3 times the upper limit of normal or Child-Pugh score A, B, and C; consider erlotinib dose reduction (in 50-mg increments), interruption, or discontinuation of therapy if severe changes in hepatic function develop