Naruo Yoshimura1, Shinzoh Kudoh2, Shigeki Mitsuoka3, Naoki Yoshimoto4, Takako Oka4, Toshiyuki Nakai4, Tomohiro Suzumira3, Kuniomi Matusura4, Yoshihiro Tochino5, Kazuhisa Asai4, Tatsuo Kimura6, Tomoya Kawaguchi3, Kazuto Hirata4. 1. Department of Clinical Oncology, Graduate School of Medicine, Osaka City University, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan; Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan. Electronic address: y-naruo@sc4.so-net.ne.jp. 2. Department of Clinical Oncology, Graduate School of Medicine, Osaka City University, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan. 3. Department of Clinical Oncology, Graduate School of Medicine, Osaka City University, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan; Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan. 4. Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan. 5. Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan; Department of Medical Education and General Practice, Graduate School of Medicine, Osaka City University, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan. 6. Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan; Department of Premier Preventive Medicine, Graduate School of Medicine, Osaka City University, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
Abstract
PURPOSE: Patients with advanced non-small cell lung cancer (NSCLC) harboring a sensitive epidermal growth factor receptor (EGFR) mutation have been shown to exhibit a marked response to EGFR-tyrosine kinase inhibitor (TKI) treatment. Pemetrexed and gefitinib were reported to have a schedule-dependent cytotoxic synergism. We evaluated the efficacy and safety of a combination regimen of gefitinib and pemetrexed as first-line chemotherapy in EGFR-mutated NSCLC patients. PATIENTS AND METHODS: Systemic therapy-naïve patients with advanced non-squamous NSCLC harboring a sensitive EGFR mutation were included in this study. Pemetrexed was administered on day 1 at a dose of 500 mg/m(2), and gefitinib was sequentially administered on days 2-16. This treatment regimen was repeated every 3 weeks until disease progression. RESULTS: Twenty-six patients were enrolled in this study. The median number of treatment cycles was 16 (range, 1-35). The overall response rate (ORR) was 84.6% (95% confidence interval [CI], 70.7-98.5%), and the disease control rate (DCR) was 96.2% (95% CI, 88.9-100%). Grade 3/4 hematological toxicities included neutropenia (15.4%), leukopenia (7.7%), and anemia (3.8%). No grade 4 non-hematological toxicities were observed. The main grade 3 non-hematological toxicities were infection (11.5%), increased alanine aminotransferase (11.5%) and aspartate aminotransferase (7.7%) levels, fatigue (3.8%), diarrhea (3.8%), and pneumonitis (3.8%). We observed a median progression-free survival (PFS) of 18.0 months (95% CI, 15.0-21.0 months) and a median survival time (MST) of 32.0 months (95% CI, 28.5-35.5 months). There were no treatment-related deaths. CONCLUSIONS: The combination regimen used in this study showed a high ORR, long median PFS, and acceptable toxicity. A future randomized trial on pemetrexed plus gefitinib compared with gefitinib alone is warranted.
PURPOSE:Patients with advanced non-small cell lung cancer (NSCLC) harboring a sensitive epidermal growth factor receptor (EGFR) mutation have been shown to exhibit a marked response to EGFR-tyrosine kinase inhibitor (TKI) treatment. Pemetrexed and gefitinib were reported to have a schedule-dependent cytotoxic synergism. We evaluated the efficacy and safety of a combination regimen of gefitinib and pemetrexed as first-line chemotherapy in EGFR-mutated NSCLCpatients. PATIENTS AND METHODS: Systemic therapy-naïve patients with advanced non-squamous NSCLC harboring a sensitive EGFR mutation were included in this study. Pemetrexed was administered on day 1 at a dose of 500 mg/m(2), and gefitinib was sequentially administered on days 2-16. This treatment regimen was repeated every 3 weeks until disease progression. RESULTS: Twenty-six patients were enrolled in this study. The median number of treatment cycles was 16 (range, 1-35). The overall response rate (ORR) was 84.6% (95% confidence interval [CI], 70.7-98.5%), and the disease control rate (DCR) was 96.2% (95% CI, 88.9-100%). Grade 3/4 hematological toxicities included neutropenia (15.4%), leukopenia (7.7%), and anemia (3.8%). No grade 4 non-hematological toxicities were observed. The main grade 3 non-hematological toxicities were infection (11.5%), increased alanine aminotransferase (11.5%) and aspartate aminotransferase (7.7%) levels, fatigue (3.8%), diarrhea (3.8%), and pneumonitis (3.8%). We observed a median progression-free survival (PFS) of 18.0 months (95% CI, 15.0-21.0 months) and a median survival time (MST) of 32.0 months (95% CI, 28.5-35.5 months). There were no treatment-related deaths. CONCLUSIONS: The combination regimen used in this study showed a high ORR, long median PFS, and acceptable toxicity. A future randomized trial on pemetrexed plus gefitinib compared with gefitinib alone is warranted.
Authors: Natalia Sutiman; Zhenxian Zhang; Eng Huat Tan; Mei Kim Ang; Shao-Weng Daniel Tan; Chee Keong Toh; Quan Sing Ng; Balram Chowbay; Wan-Teck Lim Journal: PLoS One Date: 2016-05-02 Impact factor: 3.240