A phase II study of S‑1 in relapsed small cell lung cancer

Kudo,Keita; Ohyanagi,Fumiyosi; Horiike,Atsushi; Miyauchi,Eisaku; Tahanaka,Hisashi; Yanagitani,Noriko; Saito,Ryouta; Kaburaki,Kyouhei; Sakatani,Toshio; Horai,Takeshi; Nishio,Makoto

doi:10.3892/mco.2013.67

March-April 2013 Volume 1 Issue 2

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March-April 2013 Volume 1 Issue 2

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Article

A phase II study of S‑1 in relapsed small cell lung cancer

Authors:
- Keita Kudo
- Fumiyosi Ohyanagi
- Atsushi Horiike
- Eisaku Miyauchi
- Hisashi Tahanaka
- Noriko Yanagitani
- Ryouta Saito
- Kyouhei Kaburaki
- Toshio Sakatani
- Takeshi Horai
- Makoto Nishio
View Affiliations / Copyright

Affiliations: Thoracic Oncology Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550, Japan
Pages: 263-266
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Published online on: January 14, 2013

https://doi.org/10.3892/mco.2013.67
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Abstract

S‑1 is a new oral fluoropyrimidine derivative designed to enhance anticancer activity and reduce gastrointestinal toxicity. This phase II trial aimed to evaluate S‑1 in patients with relapsed small cell lung cancer (SCLC). SCLC patients who had experienced treatment failure with ≥1 prior chemotherapies were eligible. Patients were required to have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0‑2 and adequate organ function. Treatment consisted of oral S‑1 at 40 mg/m2 twice/day for 28 days every 6 weeks. Twenty-six patients were enrolled, 85% of whom were males. The median age was 68 years (range, 33‑79) and 81% of the patients had a performance status of 0‑1, and 46% of the patients had relapse‑sensitive SCLC. An objective response was obtained in only 1 patient (3.8%), and the median progression‑free survival (PFS) was 1.1 months. The median overall survival was 5.3 months, and the 1‑year survival rate was 23%. The most common grade 3/4 toxicities included neutropenia (7.7%), leukopenia (7.7%), anemia (7.7%), hyponatremia (7.7%), rash (7.7%), infection (7.7%) and diarrhoea (3.8%). None of the patients developed febrile neutropenia and no deaths were attributed to treatment. In conclusion, S‑1 has minimal single‑agent activity in relapsed SCLC.

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1	Stupp R, Monnerat C, Turrisi AT II, Perry MC and Leyvraz S: Small cell lung cancer: state of the art and future perspectives. Lung Cancer. 45:105–117. 2004. View Article : Google Scholar : PubMed/NCBI
2	Chute JP, Chen T, Feigal E, Simon R and Johnson BE: Twenty years of phase III trials for patients with extensive-stage small-cell lung cancer: perceptible progress. J Clin Oncol. 17:1794–1801. 1999.PubMed/NCBI
3	Hurwitz JL, McCoy F, Scullin P and Fennell DA: New advances in the second-line treatment of small cell lung cancer. Oncologist. 14:986–994. 2009. View Article : Google Scholar : PubMed/NCBI
4	Shirasaka T, Yamamitsu S, Tsuji A and Taguchi T: Conceptual changes in cancer chemotherapy: from an oral fluoropyrimidine prodrug, UFT, to a novel oral fluoropyrimidine prodrug, S-1, and low-dose FP therapy in Japan. Invest New Drugs. 18:315–329. 2000. View Article : Google Scholar : PubMed/NCBI
5	Citron ML, Modeas C, Propert K, Goutsou M and Green MR: Phase II trial of high-dose 24-hour continuous intravenous 5-fluorouracil for advanced non-small cell lung cancer: a Cancer and Leukemia Group B study. Cancer Invest. 10:215–219. 1992. View Article : Google Scholar : PubMed/NCBI
6	Stewart DJ, Dahrouge S, Soltys KM and Evans WK: A phase II study of 5-fluorouracil plus high-dose folinic acid in the treatment of recurrent small cell lung cancer. Am J Clin Oncol. 18:130–132. 1995. View Article : Google Scholar : PubMed/NCBI
7	Yamamoto N, Yamanaka T, Ichinose Y, et al: Pooled analysis of S-1 trials in non-small cell lung cancer according to histological type. Anticancer Res. 30:2985–2990. 2010.PubMed/NCBI
8	Okamoto I, Yoshioka H, Morita S, et al: Phase III trial comparing oral S-1 plus carboplatin with paclitaxel plus carboplatin in chemotherapy-naive patients with advanced non-small-cell lung cancer: results of a west Japan oncology group study. J Clin Oncol. 28:5240–5246. 2010. View Article : Google Scholar : PubMed/NCBI
9	Scagliotti G, Hanna N, Fossella F, et al: The differential efficacy of pemetrexed according to NSCLC histology: a review of two Phase III studies. Oncologist. 14:253–263. 2009. View Article : Google Scholar : PubMed/NCBI
10	Socinski MA, Raju RN, Neubauer M, et al: Pemetrexed in relapsed small-cell lung cancer and the impact of shortened vitamin supplementation lead-in time: results of a phase II trial. J Thorac Oncol. 3:1308–1316. 2008. View Article : Google Scholar : PubMed/NCBI
11	Jalal S, Ansari R, Govindan R, et al: Pemetrexed in second line and beyond small cell lung cancer: a Hoosier Oncology Group phase II study. J Thorac Oncol. 4:93–96. 2009. View Article : Google Scholar : PubMed/NCBI
12	Grønberg BH, Bremnes RM, Aasebø U, et al: A prospective phase II study: high-dose pemetrexed as second-line chemotherapy in small-cell lung cancer. Lung Cancer. 63:88–93. 2009.PubMed/NCBI
13	Shirasaka T, Shimamato Y, Ohshimo H, et al: Development of a novel form of an oral 5-fluorouracil derivative (S-1) directed to the potentiation of the tumor selective cytotoxicity of 5-fluorouracil by two biochemical modulators. Anticancer Drugs. 7:548–557. 1996. View Article : Google Scholar : PubMed/NCBI
14	Adjei AA: Pemetrexed (Alimta): a novel multitargeted antifolate agent. Expert Rev Anticancer Ther. 3:145–156. 2003. View Article : Google Scholar : PubMed/NCBI
15	Hanauske AR, Eismann U, Oberschmidt O, et al: In vitro chemosensitivity of freshly explanted tumor cells to pemetrexed is correlated with target gene expression. Invest New Drugs. 25:417–423. 2007. View Article : Google Scholar : PubMed/NCBI
16	Nakano J, Huang C, Liu D, et al: Evaluations of biomarkers associated with 5-FU sensitivity for non-small-cell lung cancer patients postoperatively treated with UFT. Br J Cancer. 95:607–615. 2006. View Article : Google Scholar : PubMed/NCBI
17	Ibe T, Shimizu K, Nakano T, et al: High-grade neuroendocrine carcinoma of the lung shows increased thymidylate synthase expression compared to other histotypes. J Surg Oncol. 102:11–17. 2010. View Article : Google Scholar
18	Ceppi P, Volante M, Saviozzi S, et al: Squamous cell carcinoma of the lung compared with other histotypes shows higher messenger RNA and protein levels for thymidylate synthase. Cancer. 107:1589–1596. 2006. View Article : Google Scholar
19	Inoue K, Takao M, Watanabe F, et al: Role of dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine against non-small cell lung cancer - in correlation with the tumoral expression of thymidylate synthase and dihydropyrimidine dehydrogenase. Lung Cancer. 49:47–54. 2005. View Article : Google Scholar
20	Beck A, Etienne MC, Cheradame S, et al: A role for dihydropyrimidine dehydrogenase and thymidylate synthase in tumour sensitivity to fluorouracil. Eur J Cancer. 30A:1517–1522. 1994. View Article : Google Scholar : PubMed/NCBI
21	Shintani Y, Ohta M, Hirabayashi H, et al: Thymidylate synthase and dihydropyrimidine dehydrogenase mRNA levels in tumor tissues and the efficacy of 5-fluorouracil in patients with non-small-cell lung cancer. Lung Cancer. 45:189–196. 2004. View Article : Google Scholar : PubMed/NCBI
22	Oguri T, Achiwa H, Bessho Y, et al: The role of thymidylate synthase and dihydropyrimidine dehydrogenase in resistance to 5-fluorouracil in human lung cancer cells. Lung Cancer. 49:345–351. 2005. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

A phase II study of S‑1 in relapsed small cell lung cancer

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