Pemetrexed for Previously Treated Patients with Non-Small Cell Lung Cancer and Differences in Efficacy according to Thymidylate Synthase Expression

• Published in: Chemotherapy (Basel) Vol. 58; no. 4; pp. 313 - 320
• Main Authors: Igawa, Satoshi, Ryuge, Shinichiro, Wada, Mayuko, Otani, Sakiko, Maki, Sachiyo, Takakura, Akira, Katono, Ken, Sasaki, Jiichiro, Sato, Yuichi, Masuda, Noriyuki
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.01.2012
• Subjects: Administration, Oral; Adult; Aged; Aged, 80 and over; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - mortality; Carcinoma, Non-Small-Cell Lung - pathology; Chemotherapy; Clinical outcomes; Clinical Study; Enzymes; Female; Folic Acid - therapeutic use; Glutamates - adverse effects; Glutamates - therapeutic use; Guanine - adverse effects; Guanine - analogs & derivatives; Guanine - therapeutic use; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Leukopenia - etiology; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - mortality; Lung Neoplasms - pathology; Male; Middle Aged; Nausea - etiology; Neutropenia - etiology; Pemetrexed; Pharmacology; Salvage Therapy; Thrombocytopenia - etiology; Thymidylate Synthase - metabolism; Treatment Outcome; Thymidylate synthase; Predictive factor; Pemetrexed; Non-small cell lung cancer
• ISSN: 0009-3157; 1421-9794
• DOI: 10.1159/000343048

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.