Tina Cascone1, Kathryn A Gold2, Stephen G Swisher3, Diane D Liu4, Frank V Fossella1, Boris Sepesi3, Apar Pataer3, Annikka Weissferdt5, Neda Kalhor5, Ara A Vaporciyan3, Wayne L Hofstetter3, Ignacio I Wistuba6, John V Heymach1, Edward S Kim7, William N William8. 1. Department of Thoracic Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. 2. Department of Thoracic Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas; Department of Medicine, University of California San Diego Health, San Diego, California. 3. Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas. 4. Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas. 5. Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas. 6. Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas. 7. Department of Thoracic Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas; Department of Solid Tumor Oncology, Levine Cancer Institute, Carolinas HealthCare System, Charlotte, North Carolina. 8. Department of Thoracic Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. Electronic address: wnwillia@mdanderson.org.
Abstract
BACKGROUND: Data from meta-analyses support the use of induction or adjuvant platinum-based chemotherapy for locally advanced non-small cell lung cancers (NSCLCs). This phase 2 study assessed the role of induction cisplatin and docetaxel followed by surgery in patients with resectable stage I to III NSCLCs, followed by 12 months of adjuvant erlotinib. METHODS:Patients with resectable stage I to III NSCLCs received cisplatin 80 mg/m2, docetaxel 75 mg/m2 every 21 days for 3 cycles, followed by surgery, followed by adjuvant erlotinib for 12 months. The primary endpoint included safety. Long-term efficacy outcomes and exploratory analysis of intermediary endpoints are also reported (NCT00254384). RESULTS:Forty-seven eligible patients received a median of 3 cycles of induction treatment, 37 underwent surgical resection, and only 21 receivedadjuvant erlotinib. Two patients died in the perioperative period (1 sepsis during chemotherapy, 1 acute respiratory distress syndrome postoperatively). Most common grade 3 to 5 toxicities during chemotherapy included hypokalemia (8%), infection (7%), and granulocytopenia (25%). During adjuvant erlotinib, 14% of patients experienced grade 2 rash. Median overall survival was 3.4 years. Major pathologic responses in the primary tumor were observed in 19% (7 of 37) of patients and correlated with improved long-term overall survival. Complete pathologic response in mediastinal/hilar nodes also correlated with superior survival. CONCLUSIONS:Induction cisplatin and docetaxel was well tolerated. Adjuvant erlotinib did not improve outcomes compared with historical controls. Major pathologic response predicted for improved long-term survival and is a suitable intermediary endpoint for future phase 2 studies.
RCT Entities:
BACKGROUND: Data from meta-analyses support the use of induction or adjuvant platinum-based chemotherapy for locally advanced non-small cell lung cancers (NSCLCs). This phase 2 study assessed the role of induction cisplatin and docetaxel followed by surgery in patients with resectable stage I to III NSCLCs, followed by 12 months of adjuvant erlotinib. METHODS:Patients with resectable stage I to III NSCLCs received cisplatin 80 mg/m2, docetaxel 75 mg/m2 every 21 days for 3 cycles, followed by surgery, followed by adjuvant erlotinib for 12 months. The primary endpoint included safety. Long-term efficacy outcomes and exploratory analysis of intermediary endpoints are also reported (NCT00254384). RESULTS: Forty-seven eligible patients received a median of 3 cycles of induction treatment, 37 underwent surgical resection, and only 21 received adjuvant erlotinib. Two patients died in the perioperative period (1 sepsis during chemotherapy, 1 acute respiratory distress syndrome postoperatively). Most common grade 3 to 5 toxicities during chemotherapy included hypokalemia (8%), infection (7%), and granulocytopenia (25%). During adjuvant erlotinib, 14% of patients experienced grade 2 rash. Median overall survival was 3.4 years. Major pathologic responses in the primary tumor were observed in 19% (7 of 37) of patients and correlated with improved long-term overall survival. Complete pathologic response in mediastinal/hilar nodes also correlated with superior survival. CONCLUSIONS: Induction cisplatin and docetaxel was well tolerated. Adjuvant erlotinib did not improve outcomes compared with historical controls. Major pathologic response predicted for improved long-term survival and is a suitable intermediary endpoint for future phase 2 studies.
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