Tuberc Respir Dis.  2009 Sep;67(3):191-198.

Efficacy of Pemetrexed in Relapsed Non-Small Cell Lung Cancer and Thymidylate Synthase Expression

• Park CK
• Kim KS
• Oh IJ
• Tseden-Ish M
• Choi YD
• Kwon YS
• Kim YI
• Lim SC
• Kim YC

Abstract

BACKGROUND
Pemetrexed, a multi-targeted antifolate has been used as a second line treatment against non-small cell lung cancer (NSCLC). We aimed to clarify the efficacy and survival according to line of treatment, histologic type, and expression of thymidylate synthase (TS). METHODS: Ninety-eight patients were treated with pemetrexed as a second line treatment (n=43) or as an additional course of treatment (n=55). TS expression was studied with immunohistochemistry and graded as 0 to 3 based on the extent of expression. RESULTS: The response rate (RR) in 98 subjects was 10.2% and the disease control rate (DCR=PR+SD) was 30.6%. RR and DCR were 12.7% and 32.7% in non-squamous cell carcinoma (NSQC) compared to 7.0% and 27.9% in squamous cell carcinoma (SQC) (p>.05). No significant differences in RR and DCR were observed between a second line group (4.7%, 20.9%) and a further line group (14.5%, 38.2%). A similar trend was observed in the 88 response evaluable subjects. TS was expressed in 28.6% (grade 1), 24.5% (grade 2) and 7.1% (grade 3), respectively, and it was not expressed in 39.8% of subjects. TS expression rate was significantly higher in the SQC (72.1%) compared to NSQC (50.9%, p=0.033). However, the efficacy of pemetrexed was not significantly different by the extent of TS expression. CONCLUSION: Pemetrexed showed efficacy, not only in a second-line setting, but also in further lines of treatment for NSCLC. The efficacy of pemetrexed tended to be higher in patients with NSQC compared to SQC. TS expression rate was significantly higher in SQC compared to NSQC.

Keyword

Non-small-cell lung cancer; Pemetrexed; Thymidylate synthase

MeSH Terms

Carcinoma, Non-Small-Cell Lung
Carcinoma, Squamous Cell
Glutamates
Guanine
Humans
Immunohistochemistry
Thymidylate Synthase
Pemetrexed
Glutamates
Guanine
Thymidylate Synthase

Figure

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  Figure 1 Thymidylate synthase expression by immunohistochemical stain. (A) Grade 0 (39.8%), (B) Grade 1 (28.6%), (C) Grade 2 (24.5%), (D) Grade 3 (7.1%). ×100; Primary antibody: DAKO, Denmark, dilution 1:50.

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