Multicenter phase II trial of S-1 in patients with cytokine-refractory metastatic renal cell carcinoma

Seiji Naito, Masatoshi Eto, Nobuo Shinohara, Yoshihiko Tomita, Masato Fujisawa, Mikio Namiki, Masaharu Nishikido, Michiyuki Usami, Taiji Tsukamoto, Hideyuki Akaza

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21 Citations (Scopus)

Abstract

This phase II multicenter trial was conducted to evaluate the activity and safety of S-1 in Japanese patients with metastatic renal cell carcinoma (mRCC). We also examined the relation between response and mRNA expression levels of enzymes involved in the metabolism of fluorouracil (FU). Methods: Patients with mRCC who had received nephrectomy in whom cytokine-based immunotherapy was ineffective or contraindicated were studied. S-1 was administered orally at 80-, 100-, or 120-mg daily, assigned according to body surface area, on days 1 to 28 of a 42-day cycle. The primary end point was the objective response rate. The mRNA expression levels of FU-related enzymes were measured by reverse-transcriptase polymerase chain reaction in formalin-fixed, paraffin-embedded specimens of tumors obtained at nephrectomy. Results: A total of 45 eligible patients were enrolled. Eleven (24.4%) of 45 patients had partial responses to S-1, and 28 (62.2%) had stable disease. Median progression-free survival was 9.2 months. The severity of most adverse events was mild to moderate. The most common grade 3/4 drug-related adverse events were neutropenia (8.9%) and anorexia (8.9%). The expression level of thymidylate synthase (TS) mRNA was significantly lower in patients who responded to treatment (t-test, P = .048), and progression-free survival was significantly longer in patients whose TS mRNA expression levels were below the median value, as compared with those with higher levels (log-rank test, P = .006). Conclusion: S-1 is active against cytokine-refractory mRCC. Quantification of TS mRNA levels in tumors before treatment may facilitate prediction of the response of mRCC to S-1.

Original languageEnglish
Pages (from-to)5022-5029
Number of pages8
JournalJournal of Clinical Oncology
Volume28
Issue number34
DOIs
Publication statusPublished - Dec 1 2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Naito, S., Eto, M., Shinohara, N., Tomita, Y., Fujisawa, M., Namiki, M., Nishikido, M., Usami, M., Tsukamoto, T., & Akaza, H. (2010). Multicenter phase II trial of S-1 in patients with cytokine-refractory metastatic renal cell carcinoma. Journal of Clinical Oncology, 28(34), 5022-5029. https://doi.org/10.1200/JCO.2010.29.1203