Substitution of anti-androgens and tegafur-uracil combination therapy for castration-resistant prostate cancer: Results of a multi-center randomized phase II study

Takahashi,Masayuki; Kawabata,Rumi; Kawano,Akira; Murakami,Yoshihide; Sutou,Yasushi; Inai,Tohru; Akazawa,Seiji; Hamao,Takumi; Hayashi,Hideki; Fukawa,Tomoya; Takemura,Masahiko; Yamamoto,Yasuyo; Yamaguchi,Kunihisa; Izaki,Hirofumi; Fukumori,Tomoharu; Kanayama,Hiroomi

doi:10.3892/ijo.2013.1997

Substitution of anti-androgens and tegafur-uracil combination therapy for castration-resistant prostate cancer: Results of a multi-center randomized phase II study

Authors:
- Masayuki Takahashi
- Rumi Kawabata
- Akira Kawano
- Yoshihide Murakami
- Yasushi Sutou
- Tohru Inai
- Seiji Akazawa
- Takumi Hamao
- Hideki Hayashi
- Tomoya Fukawa
- Masahiko Takemura
- Yasuyo Yamamoto
- Kunihisa Yamaguchi
- Hirofumi Izaki
- Tomoharu Fukumori
- Hiroomi Kanayama
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Affiliations: Department of Urology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8503, Japan, Tokushima Research Center, Taiho Pharmaceutical Co. Ltd., Tokushima 771-0194, Japan, Department of Urology, Sanuki Municipal Hospital, Sanuki 769-2393, Japan, Department of Urology, Tokushima Municipal Hospital, Tokushima 770-0812, Japan, Department of Urology, Tsurugi Municipal Handa Hospital, Mima 779-4401, Japan, Department of Urology, Tokushima Prefectural Central Hospital, Tokushima 770-8539, Japan, Department of Urology, Tokushima Prefecture Naruto Hospital, Naruto 772-8503, Japan, Department of Urology, Kamei Hospital, Tokushima 770-8070, Japan, Department of Urology, Oe Kyodou Hospital, Yoshinogawa 776-8511, Japan
Published online on: June 28, 2013 https://doi.org/10.3892/ijo.2013.1997
Pages: 713-720

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Abstract

We conducted this study to determine whether substitution with anti-androgen (SOA) and tegafur-uracil (a pro‑drug of 5-FU) combination therapy is more effective than SOA alone after relapse from initial hormonal therapy. Patients who were histologically confirmed and relapsed after initial hormonal therapy were included. All patients were randomly allocated into two groups: SOA alone (group A) or SOA combined with tegafur-uracil (group B). The mRNA expression of four enzymes, including thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase (OPRT) and thymidine phosphorylase (TP), in prostate cancer cells was analyzed by quantitative reverse-transcription polymerase chain reaction. Fifty-two patients were enrolled in this study. The median age was 77 (range: 47-92) years. The PSA response rate in group B (61.5%) tended to be higher compared to that in group A (34.6%) (p=0.095). Group B (median: 15.9 months) had a significantly longer time to PSA progression (TTP) compared to group A (6.4 months) (p=0.014). In patients with a lower TS expression or a higher OPRT expression, group B demonstrated a higher PSA response rate compared to group A (p=0.019 and p=0.041, respectively). In addition, in the patients with a lower TS expression, group B demonstrated a significantly longer TTP compared to group A (p=0.018). There were no severe adverse events in either treatment group. After relapse from initial hormonal therapy, SOA combined with tegafur-uracil is effective and well tolerated. The TS mRNA expression level may be a predictive factor for this combination therapy.

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