PURPOSE: A randomized three-arm phase II study was undertaken to evaluate the optimum administration schedule of pemetrexed and gemcitabine in chemotherapy-naïve patients with non-small-cell lung cancer. PATIENTS AND METHODS: Patients were randomly assigned to three schedules of pemetrexed 500 mg/m2 plus gemcitabine 1,250 mg/m2, separated by a 90-minute interval, on a 21-day cycle as follows: schedule A, pemetrexed followed by gemcitabine on day 1 and gemcitabine on day 8; schedule B, gemcitabine followed by pemetrexed on day 1 and gemcitabine on day 8; and schedule C, gemcitabine on day 1 and pemetrexed followed by gemcitabine on day 8. RESULTS:One hundred fifty-two eligible patients (schedule A, n = 59; schedule B, n = 31, and schedule C, n = 62) received a median of five (schedule A), two (schedule B), and four (schedule C) treatment cycles. Overall, 66% of patients experienced grade 3 or 4 neutropenia. Common grade 3 and 4 nonhematologic toxicities were dyspnea (11%), fatigue (16%), and transaminase elevation (9%). Schedule A seemed less toxic compared with schedule C (grade 3 or 4 events: 86% v 94%, respectively; P = .19; grade 4 events: 39% v 48%, respectively; P = .30). Schedule B was closed at interim analysis for inferior efficacy. Schedule A, with a confirmed response rate of 31% (95% CI, 20% to 45%), met the protocol-defined efficacy criteria, whereas schedule C, with a confirmed response rate of 16.1% (95% CI, 11% to 34%), did not. Median survival time and time to progression were 11.4 and 4.4 months, respectively, with no observable difference between the arms. CONCLUSION:Pemetrexed and gemcitabine administered as outlined for schedule A met the protocol-defined efficacy criteria, was less toxic compared with the other treatment schedules, and should be further evaluated.
RCT Entities:
PURPOSE: A randomized three-arm phase II study was undertaken to evaluate the optimum administration schedule of pemetrexed and gemcitabine in chemotherapy-naïve patients with non-small-cell lung cancer. PATIENTS AND METHODS: Patients were randomly assigned to three schedules of pemetrexed 500 mg/m2 plus gemcitabine 1,250 mg/m2, separated by a 90-minute interval, on a 21-day cycle as follows: schedule A, pemetrexed followed by gemcitabine on day 1 and gemcitabine on day 8; schedule B, gemcitabine followed by pemetrexed on day 1 and gemcitabine on day 8; and schedule C, gemcitabine on day 1 and pemetrexed followed by gemcitabine on day 8. RESULTS: One hundred fifty-two eligible patients (schedule A, n = 59; schedule B, n = 31, and schedule C, n = 62) received a median of five (schedule A), two (schedule B), and four (schedule C) treatment cycles. Overall, 66% of patients experienced grade 3 or 4 neutropenia. Common grade 3 and 4 nonhematologic toxicities were dyspnea (11%), fatigue (16%), and transaminase elevation (9%). Schedule A seemed less toxic compared with schedule C (grade 3 or 4 events: 86% v 94%, respectively; P = .19; grade 4 events: 39% v 48%, respectively; P = .30). Schedule B was closed at interim analysis for inferior efficacy. Schedule A, with a confirmed response rate of 31% (95% CI, 20% to 45%), met the protocol-defined efficacy criteria, whereas schedule C, with a confirmed response rate of 16.1% (95% CI, 11% to 34%), did not. Median survival time and time to progression were 11.4 and 4.4 months, respectively, with no observable difference between the arms. CONCLUSION:Pemetrexed and gemcitabine administered as outlined for schedule A met the protocol-defined efficacy criteria, was less toxic compared with the other treatment schedules, and should be further evaluated.
Authors: Ming-Wen An; Sumithra J Mandrekar; Megan E Branda; Shauna L Hillman; Alex A Adjei; Henry C Pitot; Richard M Goldberg; Daniel J Sargent Journal: Clin Cancer Res Date: 2011-08-31 Impact factor: 12.531
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Authors: Gerold Bepler; K Eric Sommers; Alan Cantor; Xueli Li; Anupama Sharma; Charles Williams; Alberto Chiappori; Eric Haura; Scott Antonia; Tawee Tanvetyanon; George Simon; Coleman Obasaju; Lary A Robinson Journal: J Thorac Oncol Date: 2008-10 Impact factor: 15.609
Authors: An Wouters; Bea Pauwels; Filip Lardon; Greet G O Pattyn; Hilde A J Lambrechts; Marc Baay; Paul Meijnders; Jan B Vermorken Journal: BMC Cancer Date: 2010-08-19 Impact factor: 4.430
Authors: Sumithra J Mandrekar; Yingwei Qi; Shauna L Hillman; Katie L Allen Ziegler; Nicholas F Reuter; Kendrith M Rowland; Steven A Kuross; Randolph S Marks; Steven E Schild; Alex A Adjei Journal: J Thorac Oncol Date: 2010-01 Impact factor: 15.609