title: Pemetrexed and cyclophosphamide combination therapy for the treatment of non-small cell lung cancer.
abstract: Lung cancer is the leading cause of cancer-related mortality. This study was undertaken to investigate the efficacy and safety of adding regulatory T cell inhibitor cyclophosphamide to pemetrexed therapy for the second-line treatment of NSCLC with wild-type epidermal growth factor receptor (EGFR). A total of 70 patients were screened between March 2011 and December 2013, out of which 62 patients were enrolled in the study. Patients were randomized to receive 500 mg/m(2) pemetrexed in combination with 20 mg/kg cyclophosphamide in a 21 day cycle (n=30) or 500 mg/m(2) pemetrexed (n=32), and followed up for 30 months. Disease progression was observed in 23 patients in the pemetrexed plus cyclophosphamide arm and 27 patients in the pemetrexed monotherapy arm. Median progression-free survival was 3.6 months (95% confidence interval [CI], 1.3 to 5.9 months) in the pemetrexed plus cyclophosphamide arm and 2.2 months (95% CI, 1.3 to 3.1 months) in the pemetrexed monotherapy arm. The 6-month PFS rates were 22% (95% CI, 10 to 34) and 14.5% (95% CI, 6 to 23) in the pemetrexed plus cyclophosphamide arm and pemetrexed monotherapy arm, respectively. Median overall survival was 9.8 months for the pemetrexed combination therapy arm and 8.8 months for the pemetrexed arm, and the 1-year survival rates were 46% and 33%, respectively. The present study showed that pemetrexed in combination with low-dose cyclophosphamide may be a better treatment approach than pemetrexed monotherapy when considering second-line treatment for wild-type EGFR NSCLC.
authors.affiliation: Department of Cardiothoracic Surgery, Central Hospital of Zibo Zibo 250012, Shandong, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Li
authors.affiliation: Maanshan Center for Clinical Laboratory, Maanshan Municipal Hospital Group Maanshan, Anhui, China.
authors.forename: Song
authors.initials: S
authors.lastname: He
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D066246:ErbB Receptors; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D000068437:Pemetrexed / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000068437:Pemetrexed; D003520:Cyclophosphamide; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: EGFR; Non-small cell lung cancer; adenocarcinoma; second-line treatment
references.citation: Pharmacotherapy. 1997 Sep-Oct;17(5 Pt 2):146S-154S
references.pmid: 9322882
references.citation: Semin Oncol. 1992 Aug;19(4 Suppl 11):2-7
references.pmid: 1509277
references.citation: J Clin Oncol. 2010 Feb 10;28(5):744-52
references.pmid: 20038723
references.citation: Clin Cancer Res. 2010 Feb 15;16(4):1307-14
references.pmid: 20145166
references.citation: N Engl J Med. 2010 Jun 24;362(25):2380-8
references.pmid: 20573926
references.citation: Lancet Oncol. 2011 Aug;12(8):735-42
references.pmid: 21783417
references.citation: Gan To Kagaku Ryoho. 2011 Aug;38(8):1273-6
references.pmid: 21877333
references.citation: J Clin Oncol. 2011 Oct 1;29(28):3825-31
references.pmid: 21900105
references.citation: Lancet Oncol. 2012 Mar;13(3):300-8
references.pmid: 22277837
references.citation: Cancer. 2012 Dec 15;118(24):6234-42
references.pmid: 22674612
references.citation: CA Cancer J Clin. 2013 Jan;63(1):11-30
references.pmid: 23335087
references.citation: J Natl Cancer Inst. 2013 May 1;105(9):595-605
references.pmid: 23594426
references.citation: Gan To Kagaku Ryoho. 2015 Feb;42(2):183-7
references.pmid: 25743136
references.citation: Proc R Soc Med. 1970 Jan;63(1):81-4
references.pmid: 5417790
references.citation: Expert Rev Anticancer Ther. 2003 Apr;3(2):145-56
references.pmid: 12722874
references.citation: Oncol Rep. 2015 May;33(5):2411-9
references.pmid: 25738249
references.citation: N Engl J Med. 2009 Sep 3;361(10):947-57
references.pmid: 19692680