Good Response to Pemetrexed after Treatment Failure with Another Thymidylate Synthase Inhibitor in Lung Adenocarcinoma: A Case Report

Fumihiko Hirai, Eiko Inamasu, Gouji Toyokawa, Tsukihisa Yoshida, Kaname Nosaki, Tomoyoshi Takenaka, Masafumi Yamaguchi, Mitsuhiro Takenoyama, Takashi Seto, Yukito Ichinose

Department of Thoracic Oncology, National Kyushu Cancer Center, Fukuoka, Japan.

DOI: 10.4236/jct.2014.58085                

Abstract

Pemetrexed is an antimetabolic agent and is well-known as a potent inhibitor of thymidylate synthase (TS). It also inhibits dihydrofolate reductase (DHFR) and glycinamide ribonucleotide formyl transferase (GARFT). We reported an intriguing case in which a non-small cell lung cancer patient who was refractory to pretreatment with S-1, a strong TS inhibitor, showed good response to pemetrexed treatment.

Keywords

Pemetrexed, S-1, Thymidylate Synthase

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Hanna, N., Shepherd, F.A., Fossella, F.V., Pereira, J.R., De Marinis, F., von Pawel, J., Gatzemeier, U., Tsao, T.C., Pless, M., Muller, T., Lim, H.L., Desch, C., Szondy, K., Gervais, R., Shaharyar, Manegold, C., Paul, S., Paoletti, P., Einhorn, L. and Bunn Jr., P.A. (2004) Randomized Phase III Trial of Pemetrexed versus Docetaxel in Patients with Non-Small-Cell Lung Cancer Previously Treated with Chemotherapy. Journal of Clinical Oncology, 22, 1589-1597. http://dx.doi.org/10.1200/JCO.2004.08.163
[2]	Kubota, K., Sakai, H., Yamamoto, N., Kunitoh, H., Nakagawa, K., Takeda, K., Ichinose, Y., Saijo, N., Ariyoshi, Y. and Fukuoka, M. (2010) A Multi-Institution Phase I/II Trial of Triweekly Regimen with S-1 plus Cisplatin in Patients with Advanced Non-Small Cell Lung Cancer. Journal of Thoracic Oncology, 5, 702-706.
[3]	Ohe, Y., Ichinose, Y., Nakagawa, K., Tamura, T., Kubota, K., Yamamoto, N., Adachi, S., Nambu, Y., Fujimoto, T., Nishiwaki, Y., Saijo, N. and Fukuoka, M. (2008) Efficacy and Safety of Two Doses of Pemetrexed Supplemented with Folic Acid and Vitamin B12 in Previously Treated Patients with Non-Small Cell Lung Cancer. Clinical Cancer Re- search, 14, 4206-4212. http://dx.doi.org/10.1158/1078-0432.CCR-07-5143
[4]	Kubota, K., Niho, S., Enatsu, S., Nambu, Y., Nishiwaki, Y., Saijo, N. and Fukuoka, M. (2009) Efficacy Differences of Pemetrexed by Histology in Pretreated Patients with Stage IIIB/IV Non-Small Cell Lung Cancer: Review of Results from an Open-Label Randomized Phase II Study. Journal of Thoracic Oncology, 4, 1530-1536. http://dx.doi.org/10.1097/JTO.0b013e3181b9e608
[5]	Landis, D.M., Heindel, C.C. and Loeb, L.A. (2001) Creation and Characterization of 5-Fluorodeoxyuridine-Resistant Arg50 Loop Mutants of Human Thymidylate Synthase. Cancer Research, 61, 666-672.
[6]	Shih, C., Chen, V.J., Gossett, L.S., Gates, S.B., MacKellar, W.C., Habeck, L.L., Shackelford, K.A., Mendelsohn, L.G., Soose, D.J., Patel, V.F., Andis, S.L., Bewley, J.R., Rayl, E.A., Moroson, B.A., Beardsley, G.P., Kohler, W., Ratnam, M. and Schultz, R.M. (1997) LY231514, a Pyrrolo[2,3-d]Pyrimidine-Based Antifolate That Inhibits Multiple Folate-Requiring Enzymes. Cancer Research, 57, 1116-1123.