Purpose: To evaluate the efficacy and safety of alternating gefitinib and erlotinib, tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR), with chemotherapy in non-small-cell lung cancer (NSCLC) patients with acquired TKI resistance.
Methods: Forty-two patients with lung cancer that responded to TKIs for as least 6 months before developing TKI resistance were enrolled and received sequential pemetrexed or pemetrexed plus platinum followed by gefitinib or erlotinib. Chemotherapy was intravenously administered on day 1, and patients were provided oral EGFR-TKIs between days 6 and 21. The treatment was repeated every 3 weeks for 2 to 4 cycles. At the end of the specified treatment regimen, patients continued to receive EGFR-TKIs for maintenance until disease progression or unacceptable toxicity. The primary end point was the disease control rate. Secondary end points included overall remission rate, median progression-free survival, and survival rate.
Results: The disease control rate was 78.6%, the overall remission rate was 23.8%, and survival rate was 73.8%. Progression-free survival was 8 months, and median survival time was 11 months. The treatment protocol was generally well tolerated. Treatment interruption was required in 2 patients. Grade 3/4 hematologic toxicities included neutropenia (23.8%), leukopenia (16.7%), anemia (4.8%), and thrombocytopenia (4.8%). Common grade 3 nonhematologic toxicities included nausea (7.1%), vomiting (9.5%), anorexia (11.9%), rash (7.1%), fatigue (9.5%), infection (16.7%), and oral mucositis (2.4%). No toxicity-related deaths occurred.
Conclusions: For patients with acquired TKI resistance, pemetrexed or pemetrexed plus platinum administration followed by gefitinib or erlotinib was well tolerated and associated with a fair response.
Keywords: Acquired resistance; Non–small-cell lung cancer; Pemetrexed; Platinum; Progression-free survival.
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