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

Research output: Contribution to journalArticle

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

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Renal Cell Carcinoma
Cytokines
Thymidylate Synthase
Messenger RNA
Nephrectomy
Fluorouracil
Disease-Free Survival
Body Surface Area
Anorexia
Enzymes
Neutropenia
Drug-Related Side Effects and Adverse Reactions
Reverse Transcriptase Polymerase Chain Reaction
Paraffin
Immunotherapy
Formaldehyde
Multicenter Studies
Neoplasms
Safety
Therapeutics

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Multicenter phase II trial of S-1 in patients with cytokine-refractory metastatic renal cell carcinoma. / Naito, Seiji; Eto, Masatoshi; Shinohara, Nobuo; Tomita, Yoshihiko; Fujisawa, Masato; Namiki, Mikio; Nishikido, Masaharu; Usami, Michiyuki; Tsukamoto, Taiji; Akaza, Hideyuki.

In: Journal of Clinical Oncology, Vol. 28, No. 34, 01.12.2010, p. 5022-5029.

Research output: Contribution to journalArticle

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, vol. 28, no. 34, pp. 5022-5029. https://doi.org/10.1200/JCO.2010.29.1203
Naito, Seiji ; Eto, Masatoshi ; Shinohara, Nobuo ; Tomita, Yoshihiko ; Fujisawa, Masato ; Namiki, Mikio ; Nishikido, Masaharu ; Usami, Michiyuki ; Tsukamoto, Taiji ; Akaza, Hideyuki. / Multicenter phase II trial of S-1 in patients with cytokine-refractory metastatic renal cell carcinoma. In: Journal of Clinical Oncology. 2010 ; Vol. 28, No. 34. pp. 5022-5029.
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AU - Fujisawa, Masato

AU - Namiki, Mikio

AU - Nishikido, Masaharu

AU - Usami, Michiyuki

AU - Tsukamoto, Taiji

AU - Akaza, Hideyuki

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