title: Pemetrexed for previously treated patients with non-small cell lung cancer and differences in efficacy according to thymidylate synthase expression.
abstract: The purpose of this study was to evaluate the efficacy of pemetrexed monotherapy in previously treated patients with advanced non-small cell lung cancer (NSCLC) including salvage treatment, and to evaluate whether thymidylate synthase (TS) expression is a predictor for pemetrexed efficacy. Hundred and four previously treated patients with advanced NSCLC who received pemetrexed monotherapy were retrospectively evaluated for clinical efficacy and toxicity. If available, tissue specimens of patients were also analyzed immunohistochemically for TS expression. The patients' median age was 65 years (range: 43-82). An overall response rate of 9.6% and a median progression-free survival (PFS) time of 3.4 months were achieved. The response rates for the second-line, third-line, fourth-line or further treatments were 9.1, 9.3 and 10.2% (p = 0.33); the median PFS were 3.3, 3.2 and 3.8 months (p = 0.21). The median follow-up duration was 14.9 months; the median overall survival (OS) was 11.9 months. The median PFS and OS were significantly longer in the TS-negative group than in the TS-positive group (5.8 months vs. 1.6 months; p = 0.03, and 14.7 months vs. 8.6 months; p = 0.04, respectively). Pemetrexed monotherapy could be considered as an option in the fourth or later lines of treatment of previously treated patients with advanced NSCLC as well as a second- or third-line treatment, and TS expression may be a potentially predictive factor for pemetrexed efficacy in NSCLC patients.
authors.affiliation: Department of Respiratory Medicine, Kitasato University School of Medicine, Sagamihara, Japan. igawa@kitasato-u.ac.jp
authors.forename: Satoshi
authors.initials: S
authors.lastname: Igawa
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Ryuge
authors.forename: Mayuko
authors.initials: M
authors.lastname: Wada
authors.forename: Sakiko
authors.initials: S
authors.lastname: Otani
authors.forename: Sachiyo
authors.initials: S
authors.lastname: Maki
authors.forename: Akira
authors.initials: A
authors.lastname: Takakura
authors.forename: Ken
authors.initials: K
authors.lastname: Katono
authors.forename: Jiichiro
authors.initials: J
authors.lastname: Sasaki
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Sato
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Masuda
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D005260:Female; D005492:Folic Acid / Q000627:therapeutic use; D005971:Glutamates / Q000009:adverse effects / Q000627:therapeutic use*; D006147:Guanine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D007970:Leukopenia / Q000209:etiology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000209:etiology; D009503:Neutropenia / Q000209:etiology; D000068437:Pemetrexed; D016879:Salvage Therapy; D013921:Thrombocytopenia / Q000209:etiology; D013940:Thymidylate Synthase / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine; D005492:Folic Acid; D013940:Thymidylate Synthase