BACKGROUND: In our 2007 retrospective study, we reported that single nucleotide polymorphisms (SNPs) in the signal transducer and activator of transcription 3 (acute-phase response factor) (STAT3) gene were significantly associated with better response to interferon (IFN)-α in patients with metastatic renal cell carcinoma (mRCC).
OBJECTIVE: To prospectively confirm those results, the Japan Immunotherapy SNPs-Study Group for Kidney Cancer conducted this trial.
DESIGN, SETTING, AND PARTICIPANTS: In this multicenter, prospective study, 203 eligible patients were enrolled. We evaluated the correlation between the antitumor effects of IFN-α and 11 SNPs (STAT3-2, STAT3-0, SOCS3-1, IL4R-34, PTGS1-3, PTGS1-4, PTGS1-5, PTGS2-12, IRF2-67, ICSBP-38, and TAP2-5) in eight genes in 180 patients who received IFN-α for >12 wk.
INTERVENTIONS: Patients were treated with three doses per week of IFN-α 5 million IU.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We analyzed the association of response to IFN-α and overall survival (OS) with genetic polymorphisms using a chi-square test and a logistic regression model.
RESULTS AND LIMITATIONS: The response rate of IFN-α was 13.8% (28 of 203 patients; 9 complete responses [CRs], 19 partial responses [PRs]). The CR rate of 4.4% was higher than we expected. Response to IFN-α was not associated with any of the 11 SNPs examined. However, when we assessed patients with CR, PR, and stable disease >24 wk as a group representing those with clinical response, a significant association was observed between STAT3-2 (rs1905341) and the clinical response of IFN-α (p=0.039). Namely, C/C genotype of STAT3-2 was significantly associated with the clinical response of IFN-α and OS. These results were generated in Japanese patients and should be studied in other ethnic groups.
CONCLUSIONS: This is the first prospective study demonstrating that a STAT3 polymorphism can be a predictive marker for treatment with IFN-α for patients with mRCC.
Written by:
Eto M, Kamba T, Miyake H, Fujisawa M, Kamai T, Uemura H, Tsukamoto T, Azuma H, Matsubara A, Nishimura K, Nakamura T, Ogawa O, Naito S. Are you the author?
Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Urology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
Reference: Eur Urol. 2012 Sep 28. pii: S0302-2838(12)01120-7.
doi: 10.1016/j.eururo.2012.09.052
PubMed Abstract
PMID: 23063454
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