The latest article in our Clinical Therapeutics series, Treatment of Non-Small-Cell Lung Cancer with Erlotinib or Gefitinib, comes from Dr. Vince Cataldo at the Louisiana State University Health Sciences Center and Hematology–Oncology Clinic, Drs. Don Gibbons and Alfonso Quintás-Cardama at Montefiore Medical Center, and Dr. Román Pérez-Soler at Albert Einstein College of Medicine.
Advanced-stage non-small-cell lung cancer (NSCLC) is currently considered an incurable disease for which standard chemotherapy provides marginal improvement in overall survival at the expense of substantial morbidity and mortality. Even with the addition of newer agents, such as bevacizumab, to chemotherapy, the median overall survival of patients with metastatic NSCLC remains approximately 1 year.
• Which patients with non-small-cell lung cancer appear to benefit most substantially from treatment with erlotinib or gefitinib?
The available trial data suggest that EGFR tyrosine kinase inhibitors have efficacy that is similar to that of standard chemotherapy as second- or third-line treatment for patients with advanced NSCLC. Among patients receiving first-line therapy, tyrosine kinase inhibitors appear to be inferior to standard chemotherapy overall but superior for selected patients, especially for those with activating EGFR mutations.
• For how long should treatment with erlotinib or gefitinib be continued?
Daily erlotinib or gefitinib therapy should be continued for as long as the patient’s performance status is adequate and there is no clinical or radiographic progression, since patients with stable disease have been shown to derive clinical benefit. Furthermore, data support the continuation of treatment even if a loss of response is documented, since tumor progression is accelerated to a greater degree if the agent is discontinued.
Morning Report Questions
Q: Concurrent treatment with which medications should be avoided in patients being treated with erlotinib or gefitinib?
A: The solubility of both erlotinib and gefitinib is pH dependent. Agents that alter gastric pH, such as H2-receptor antagonists and proton-pump inhibitors, can substantially reduce the plasma levels of the EGFR tyrosine kinase inhibitors, and their concomitant use should be avoided.
Q: What is the most common dose-limiting adverse effect that limits erlotinib or gefitinib dosing?
A: In phase 1 studies of both agents, diarrhea was the dose-limiting effect. Diarrhea occurs in up to 55% of patients who are treated with erlotinib, with severe diarrhea occurring in 6% of patients. The incidence of diarrhea in patients receiving gefitinib ranges from 27 to 35%. Unlike traditional cytotoxic agents, erlotinib and gefitinib do not typically cause myelosuppression, neuropathy, alopecia, or severe nausea.