A human epidermal growth factor receptor (EGFR) Type I tyrosine kinase inhibitor.
Oral agent that is a potent reversible EGFR tyrosine kinase inhibitor.
Targets the EGFR domain.
Bioavailability increased by food.
Should be taken at least one hour before or 2 hours after food ingestion.
About 60% absorbed after oral administration.
Median half life of 36.2 hours and smokers have a 24% higher clearance rate.
Cleared predominantly by the liver.
In a study 2911 patients with solid malignancies from 9 randomized control trials, overall incidence of skin rash was 70.4%, with 9.4% being high-grade(Jia Y).
In the above study there was a significant increase risk of rash when the agent was used alone, in the incidence was significantly less inpatients treated with a combination erlotinib and chemotherapy.
Major side effects reported in various trials including skin toxicity, dry skin, hair growth disorders, pruritus and nail changes.
Most common skin toxicity of tyrosine kinase inhibitors is a acne-like rash.
Oral tetracycline or its analogues doxycycline and minocycline have shown benefit with the prophylactic use of these agents and randomized control trials.
It is suggested that EGFR inhibition by this agent results of impaired growth in migration of keratinocytes and increased production of chemokines, which leads to the recruitment of inflammatory cells and cutaneous injury.
Use of 150 mg daily oral dose in non-small cell lung cancer patients who had previously received chemotherapy results in a 8.9% response rate with a median survival of 6.7 months and median duration of response of 34.4 weeks, a result significantly improved over placebo managed patients.
In non-small cell lung cancer in patients over the age of 79 years daily treatment associated with 12% partial response and stable disease in 48% of patients with a median survival of 11 months.
Prolongs survival in EGFR+ patients and in those who never smoked and especially in non smoker EGFR+ patients.
Currently the standard of care for frontline treatment of patients whose tumors have an activating mutation of the EGFR domain.
Erlotinib (Tarceva)indicated for the first line treatment of patients with metastatic non-small cell lung cancer whose tumors have epidermal growth factor receptor exon 19 deletions or exon 21 substitute mutations.
Despite chemotherapy response rate in the 50-70% range, the median progression free survival is about 9 to 10 months in most studies and in most patients with EGFR mutant tumors have disease progression by one year, mostly because the development of resistance of multiple different pathways.
SATURN (Sequential Tarceva in Unresectable Non-Small Lung Cancer) a maintenance trial in patients with advanced, inoperable, metastatic NSCLC treated with first-line platinum based doublet-responders treated with erlotinib or placebo: greatest benefit in patients with EGFR mutation positive group with a 90% reduction in the risk of disease progression compared to placebo, but only 11% had such a mutation.
Smoking history more predictive of survival benefit in NSCLC from erlotinib than EGFR expression status.
Rash and diarrhea most common adverse reactions with grade 3/4 events occurring in 9% and 6% of cases, respectively.
Median time to onset of rash is 8 days and 12 days for onset to diarrhea.
Recommended dose 150 mg/day.
No clinical benefit with use of additional chemotherapy in non small cell carcinoma of the lung.
Rarely associated with serious interstitial lung disease (0.6%).
Treatment should be stopped if patients experience new or unexplained cough, dyspnea or fever.
Gastrointestinal perforation, bullous, blistering and exfoliate skin processes including Stevens-Johnson syndrome, toxic epidermal necrolysis, corneal perforation or ulceration have been reported.
Use of concomitant anti-antiangiogenic agents, corticosteroids, NSAIDs, and taxane based chemotherapy associated with increased risk of skin and eye complications.
Patients with adenocarcinoma, women and Asian patients do well.
Patients with bronchioalveolar cancer likely to benefit.
Asymptomatic increases in liver transaminases have been observed.