Randomized Phase II Trial of Three Schedules of Pemetrexed and Gemcitabine As Front-Line Therapy for Advanced Non–Small-Cell Lung Cancer

• Published in: Journal of clinical oncology Vol. 23; no. 25; pp. 5929 - 5937
• Main Authors: MA, Cynthia X, NAIR, Suresh, JETT, James R, OBASAJU, Coleman, ADJEI, Alex A, THOMAS, Sachdev, MANDREKAR, Sumithra J, NIKCEVICH, Daniel A, ROWLAND, Kendrith M, FITCH, Tom R, WINDSCHITL, Harold E, HILLMAN, Shauna L, SCHILD, Steven E
• Format: Journal Article
• Language: English
• Published: Baltimore, MD American Society of Clinical Oncology 01.09.2005; Lippincott Williams & Wilkins
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - pathology; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; Disease Progression; Drug Administration Schedule; Female; Glutamates - administration & dosage; Guanine - administration & dosage; Guanine - analogs & derivatives; Humans; Infusions, Intravenous; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Male; Medical sciences; Middle Aged; Pemetrexed; Pneumology; Survival Analysis; Treatment Outcome; Tumors; Tumors of the respiratory system and mediastinum; Antineoplastic agent; Lung disease; Gemcitabine; Respiratory disease; Lung cancer; Malignant tumor; non-small cell lung carcinoma; Pemetrexed; Antifolate; Cancerology; Treatment; Antimetabolic; Phase II trial; Bronchus disease; Pyrimidine derivatives; Clinical trial; Advanced stage; Fluorine Organic compounds; Pyrimidine nucleoside
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2005.13.953

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 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. 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. 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.