INTRODUCTION: Epidermal growth factor receptor tyrosine kinase inhibitors given concurrently with chemotherapy do not improve patient outcomes compared with chemotherapy alone in advanced non-small cell lung cancer (NSCLC). Pharmacodynamic separation by intermittent delivery of epidermal growth factor receptor tyrosine kinase inhibitors with chemotherapy may increase efficacy by overcoming hypothesized antagonism. METHODS: Two dose-escalating phase I trials (arm A and arm B) were conducted simultaneously. Pemetrexed was given every 21 days (500 mg/m intravenously). In arm A, erlotinib was given weekly on days 2, 9, and 16 (800-1400 mg). In arm B, erlotinib was given on days 2 to 16 (150-250 mg). Patients continued therapy until disease progression or unacceptable toxicity. RESULTS:Forty-two patients with advanced solid tumors, including 16 NSCLC, were treated. Patient characteristics included median age of 63 (range, 29-77), 19 males, and Karnofsky performance status >or=90/<90 = 27/15. The median number of cycles was 2. Treatment was well tolerated. Planned dose escalation was completed without reaching a maximum tolerated dose. Dose-limiting toxicities included grade 3 infection/fever (arm A: 500/1200) and grade 3 infection/neutropenia (arm B: 500/150). Rash frequency was 55% in arm A and 90% in arm B. There were six partial responses (four lung, one head and neck, one breast) and 16 stable diseases. Four patients with NSCLC remained on therapy for 9, 16, 16, and 22 cycles. CONCLUSIONS: We report the first clinical trial to test intermittent erlotinib plus pemetrexed. Pemetrexed 500 mg/m and weekly erlotinib 1400 mg (arm A) or pemetrexed 500 mg/m and erlotinib 250 mg on days 2 to 16 (arm B) are feasible and well tolerated. Arm B efficacy is being examined in a randomized phase II trial for second-line NSCLC.
RCT Entities:
INTRODUCTION:Epidermal growth factor receptor tyrosine kinase inhibitors given concurrently with chemotherapy do not improve patient outcomes compared with chemotherapy alone in advanced non-small cell lung cancer (NSCLC). Pharmacodynamic separation by intermittent delivery of epidermal growth factor receptor tyrosine kinase inhibitors with chemotherapy may increase efficacy by overcoming hypothesized antagonism. METHODS: Two dose-escalating phase I trials (arm A and arm B) were conducted simultaneously. Pemetrexed was given every 21 days (500 mg/m intravenously). In arm A, erlotinib was given weekly on days 2, 9, and 16 (800-1400 mg). In arm B, erlotinib was given on days 2 to 16 (150-250 mg). Patients continued therapy until disease progression or unacceptable toxicity. RESULTS: Forty-two patients with advanced solid tumors, including 16 NSCLC, were treated. Patient characteristics included median age of 63 (range, 29-77), 19 males, and Karnofsky performance status >or=90/<90 = 27/15. The median number of cycles was 2. Treatment was well tolerated. Planned dose escalation was completed without reaching a maximum tolerated dose. Dose-limiting toxicities included grade 3 infection/fever (arm A: 500/1200) and grade 3 infection/neutropenia (arm B: 500/150). Rash frequency was 55% in arm A and 90% in arm B. There were six partial responses (four lung, one head and neck, one breast) and 16 stable diseases. Four patients with NSCLC remained on therapy for 9, 16, 16, and 22 cycles. CONCLUSIONS: We report the first clinical trial to test intermittent erlotinib plus pemetrexed. Pemetrexed 500 mg/m and weekly erlotinib 1400 mg (arm A) or pemetrexed 500 mg/m and erlotinib 250 mg on days 2 to 16 (arm B) are feasible and well tolerated. Arm B efficacy is being examined in a randomized phase II trial for second-line NSCLC.
Authors: David R Gandara; Tianhong Li; Primo N Lara; Karen Kelly; Jonathan W Riess; Mary W Redman; Philip C Mack Journal: Clin Lung Cancer Date: 2013-10-12 Impact factor: 4.785
Authors: Tianhong Li; Bilal Piperdi; William V Walsh; Mimi Kim; Laurel A Beckett; Rasim Gucalp; Missak Haigentz; Venu G Bathini; Huiyu Wen; Kaili Zhou; Patricia B Pasquinelli; Srikanth Gajavelli; Meera Sreedhara; Xianhong Xie; Primo N Lara; David R Gandara; Roman Perez-Soler Journal: Clin Lung Cancer Date: 2016-10-28 Impact factor: 4.785
Authors: Randeep Sangha; Angela M Davies; Primo N Lara; Philip C Mack; Laurel A Beckett; Paul J Hesketh; Derick Lau; Tianhong Li; Natasha Perkins; David R Gandara Journal: J Thorac Oncol Date: 2011-12 Impact factor: 15.609
Authors: Thomas Semrad; Afsaneh Barzi; Heinz-Josef Lenz; Irene M Hutchins; Edward J Kim; I-Yeh Gong; Michael Tanaka; Laurel Beckett; William Holland; Rebekah A Burich; Leslie Snyder-Solis; Philip Mack; Primo N Lara Journal: Int J Clin Oncol Date: 2014-08-05 Impact factor: 3.402