|
Advertisement |
|
|
||
 |
|
|||||
|
|||||
|
 |
||||||
|
||||||
|
||||||
|
Originally published as JCO Early Release 10.1200/JCO.2009.23.6406 on October 19 2009 © 2010 American Society of Clinical Oncology. Phase II Trial of Pemetrexed Plus Bevacizumab for Second-Line Therapy of Patients With Advanced Non–Small-Cell Lung Cancer: NCCTG and SWOG Study N0426From Roswell Park Cancer Institute, Buffalo, NY; Mayo Clinic Rochester, Rochester, MN; University of California, Davis Cancer Center, Sacramento, CA; Michigan Cancer Research Consortium, Ann Arbor, MI; Carle Cancer Center Community Clinical Oncology Program, Urbana, IL; Mayo Clinic Arizona, Scottsdale, AZ; and The University of Texas M. D. Anderson Cancer Center, Houston, TX. Corresponding author: Alex A. Adjei, MD, PhD, Roswell Park Cancer Institute, Elm & Carlton Sts, Buffalo, NY 14263; e-mail: alex.adjei{at}roswellpark.org. Purpose To evaluate the efficacy and toxicity of pemetrexed combined with bevacizumab as second-line therapy for patients with advanced non–small-cell lung cancer (NSCLC) and to correlate allelic variants in pemetrexed-metabolizing genes with clinical outcome. Patients and Methods Patients with previously treated NSCLC received pemetrexed (500 mg/m2 intravenous) combined with bevacizumab (15 mg/kg intravenous) every 3 weeks. The primary end point, evaluated using a one-stage Fleming design for detecting a true success rate of at least 70%, was the proportion of patients who were progression free and on treatment at 3 months. Polymorphisms in genes responsible for pemetrexed transport (reduced folate carrier [SLC19A1]) and metabolism (folylpolyglutamate synthase [FPGS] and gamma-glutamyl hydrolase [GGH]) evaluated in germline DNA (blood) were correlated with treatment outcome.
Results Forty-eight evaluable patients (14 females and 34 males) received a median of four cycles (range, one to 20 cycles). The most common grade 3 or 4 nonhematologic adverse events (AEs) were fatigue (13%), dyspnea (10%), and thrombosis (10%). Grade 3 or 4 hematologic AEs were neutropenia (19%) and lymphopenia (13%). Twenty-four (57%; 95% CI, 41% to 72%) of the first 42 patients met the success criteria. Median overall survival (OS) and progression-free survival (PFS) times were 8.6 and 4.0 months, respectively. The exon 6 (2522)C Conclusion The study did not meet its primary end point. However, the median PFS time of 4 months is promising. Pharmacogenetic studies in larger cohorts are needed to definitively identify polymorphisms that predict for survival and toxicity of pemetrexed. This study was conducted as a collaborative trial of the North Central Cancer Treatment Group, Mayo Clinic, and Southwest Oncology Group. Supported in part by Public Health Service Grants No. CA-25224, CA-37404, CA-32291, CA-35267, CA-63848, CA-35113, CA-35103, CA-35432, CA-35269, CA-35195, CA-35119, CA-52352, CA-35090, CA-63844, and CA-35195 and by the National Cancer Institute, Genentech, and Eli Lilly. Presented in part at the 44th Annual Meeting of the American Society of Clinical Oncology, May 30-June 3, 2008, Chicago, IL. The contents of this article are solely the responsibility of the authors and do not necessarily represent the views of the National Cancer Institute or the National Institutes of Health. Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article. Clinical trial information can be found for the following: NCT00268489 [ClinicalTrials.gov] .
This article has been cited by other articles:
|
||||||||||||||||||||||||
|
|
|||||||||||
|
|||||||||||
|
|
Copyright © 2010 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
|
T polymorphism in SLC19A1 correlated with 3-month progression-free status (P = .01) and with PFS (P = .05). The IVS1(1307)C
