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Park, Kim, Oh, Tseden-Ish, Choi, Kwon, Kim, Lim, and Kim: Efficacy of Pemetrexed in Relapsed Non-Small Cell Lung Cancer and Thymidylate Synthase Expression
Original Article
Tuberculosis and Respiratory Diseases

Tuberculosis and Respiratory Diseases 2009; 67(3): 191-198.

Published online: 30 September 2009

DOI: https://doi.org/10.4046/trd.2009.67.3.191

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

Choel-Kyu Park, M.D.1, Kyu-Sik Kim, M.D.1, In-Jae Oh, M.D.1, Manaljav Tseden-Ish, M.D.1, 3, Yoo-Duk Choi, M.D.2, Yong-Soo Kwon, M.D.1, Yoo-Il Kim, M.D.1, Sung-Chul Lim, M.D.1, Young-Chul Kim, M.D.1

1Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea.

2Department of Pathology, Chonnam National University Medical School, Gwangju, Korea.

3The Brain Korea 21 Project, Center for Biomedical Human Resources at Chonnam National University, Gwangju, Korea.

Address for correspondence: Young-Chul Kim, M.D. Lung and Esophageal Cancer Clinic, Chonnam National University Hwasun Hospital, 160, Ilsim-ri, Hwasun-eup, Hwasun-gun, Jeonnam 519-809, Korea. Phone: 82-61-379-7614, Fax: 82-61-379-7628, kyc0923@chonnam.ac.kr

Received 10 July 2009       Accepted 25 August 2009

Copyright©2009. The Korean Academy of Tuberculosis and Respiratory Diseases. All rights reserved.

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.

Keywords: Non-small-cell lung cancer, Pemetrexed, Thymidylate synthase

Figures and Tables

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.
trd-67-191-g001
Table 1
Characteristics of patients and efficacy to pemetrexed
trd-67-191-i001

*Adenocarcinoma, †Include large cell carcinoma, bronchoalveolar carcinoma, and etc., ‡Intention to treatment population, §Response evaluable population.

Table 2
Efficacy of pemetrexed according to histologic types and lines of treatment
trd-67-191-i002

All the data did not show significant differences (p>0.05).

*Disease control=Partial response+Stable disease, †Squamous cell carcinoma, ‡Non-squamous cell carcinoma, §Intention to treatment population,∥Response evaluable population.

Table 3
Thymidylate synthase expression and correlation with histologic types and efficacy to pemetrexed
trd-67-191-i003

*p<0.05, †Squamous cell carcinoma, ‡Non-squamous cell histology, §Disease control=Partial response+Stable disease, ∥Intention to treatment population, Response evaluable population.

Table 4
Overall survival (OS) and progression free survival (PFS) according to histologic type, lines of treatment and expression of thymidylate synthase (TS)
trd-67-191-i004

*Squamous cell carcinoma, †Non-squamous cell histology.

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