Prospective Assessment of Continuation of Erlotinib or Gefitinib in Patients with Acquired Resistance to Erlotinib or Gefitinib Followed by the Addition of Pemetrexed

• Published in: Journal of thoracic oncology Vol. 8; no. 1; pp. 96 - 101
• Main Authors: Yoshimura, Naruo, Okishio, Kyoichi, Mitsuoka, Shigeki, Kimura, Tatsuo, Kawaguchi, Tomoya, Kobayashi, Masaji, Hirashima, Tomonori, Daga, Haruko, Takeda, Koji, Hirata, Kazuto, Kudoh, Shinzoh
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2013; International Association for the Study of Lung Cancer
• Subjects: Acquired resistance; Aged; Aged, 80 and over; Anemia - chemically induced; Anorexia - chemically induced; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Confidence Intervals; Disease-Free Survival; Drug Resistance, Neoplasm; Epidermal growth factor receptor mutation; Erlotinib; Erlotinib Hydrochloride; Fatigue - chemically induced; Female; Gefitinib; Glutamates - administration & dosage; Guanine - administration & dosage; Guanine - analogs & derivatives; Humans; Infection - chemically induced; Kaplan-Meier Estimate; Leukopenia - chemically induced; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Male; Middle Aged; Neutropenia - chemically induced; Non–small-cell lung cancer; Pemetrexed; Protein Kinase Inhibitors - therapeutic use; Quinazolines - administration & dosage; Receptor, Epidermal Growth Factor - antagonists & inhibitors; Receptor, Epidermal Growth Factor - genetics; Non–small-cell lung cancer; Epidermal growth factor receptor mutation; Acquired resistance; Erlotinib; Gefitinib; Pemetrexed
• ISSN: 1556-0864; 1556-1380
• DOI: 10.1097/JTO.0b013e3182762bfb

Patients with epidermal growth factor receptor (EGFR) mutation positive non–small-cell lung cancer exhibited marked response to gefitinib or erlotinib. In most cases, however, the patients showed disease progression after EGFR-tyrosine kinase inhibitor (TKI) treatment. We evaluated the efficacy and safety of pemetrexed in combination with EGFR-TKI in patients with disease progression. Patients with EGFR-mutant stage IIIB or IV non–small-cell lung cancer that progressed during gefitinib or erlotinib therapy were administered pemetrexed with the continuation of EGFR-TKI treatment. Pemetrexed was administered on day 1 at a dose of 500 mg/m2, and EGFR-TKI was sequentially administered on days 2 to 16. This treatment was repeated every 3 weeks until disease progression. The primary endpoint was disease control rate. Twenty-seven patients were enrolled in this study. The median number of treatment cycles was six. Overall response rate was 25.9% (95% confidence interval, 9.4%–42.4%) and disease control rate was 77.8% (95% confidence interval, 62.1%–93.5%). Grade 3/4 hematological toxicities were neutropenia (22.2%), leukopenia (14.8%), and anemia (7.4%). Grade 4 nonhematological toxicities were not observed. Major grade 3 nonhematological toxicities were anorexia (14.8%), infection (14.8%), and fatigue (11.1%). The median progression-free survival was 7.0 months, and median survival time was 11.4 months. No treatment-related deaths occurred. Pemetrexed in combination with erlotinib or gefitinib after disease progression shows favorable response and acceptable toxicity.