Docetaxel, low-dose estramustine, and doxifluridine in hormone-refractory metastatic prostate cancer

Yoshihiro Wada, Ken Kikuchi, Wataru Takahashi, Jiro Honda, Juro Nakanishi, Koichiro Matsumoto, Tomohiro Kuwahara, Nobuyuki Kai, Hiroaki Kikukawa, Shoichi Ueda

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Purpose: Advanced prostate cancer, which is one of the most common cancers, usually progresses to hormone-refractory prostate cancer (HRPC). A recent randomized trial of treatment with docetaxel demonstrated improved survival for patients with HRPC. The combination of docetaxel and estramustine phosphate (estramustine) has been reported to be effective for HRPC. Low-dose estramustine suppresses the pituitary-gonadal axis. Docetaxel plus 5-fluoro-5′- deoxyuridine (5′-dFUrd) had supra-additive cytotoxic effects on HRPC cells consistent with the molecular mechanism. Therefore, we examined the efficacy of adding 5′-dFUrd on the chemotherapy regimen, which consist docetaxel and estramustine. Methods: All of the HRPC patients were treated with estramustine 140 mg orally twice 5′-dFUrd 200 mg orally four times daily on days 1-21, and docetaxel 60 mg/m2 was administered on day 1. We evaluated serum prostate-specific antigen (PSA) and measurable responses, the progression-free and overall survival, and the impact on adverse effects and the quality of life (QOL). Results: Of 34 patients with a median age of 72.3 years, 73% showed PSA responses and 70% showed measurable responses. The median progression-free survival was 18.0 and 5.8 months for PSA responders and non-responders and the overall survival was 19.4 months, respectively. There were few serious adverse effects. Grade 3/4 neutropenia occurred in 32.4% of the patients, and was easily managed with granulocyte colony-stimulating factor (G-CSF) injection. There was no significant change in the overall QOL scores serially. Conclusions: This study shows that the combined regimen is tolerable and effective in Japanese HRPC patients.

Original languageEnglish
Pages (from-to)53-61
Number of pages9
JournalCancer chemotherapy and pharmacology
Volume61
Issue number1
DOIs
Publication statusPublished - Jan 1 2008

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docetaxel
Estramustine
Refractory materials
Prostatic Neoplasms
Hormones
Prostate-Specific Antigen
Disease-Free Survival
Quality of Life
Chemotherapy
Granulocyte Colony-Stimulating Factor
Survival
doxifluridine
Neutropenia
Phosphates

All Science Journal Classification (ASJC) codes

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

Cite this

Docetaxel, low-dose estramustine, and doxifluridine in hormone-refractory metastatic prostate cancer. / Wada, Yoshihiro; Kikuchi, Ken; Takahashi, Wataru; Honda, Jiro; Nakanishi, Juro; Matsumoto, Koichiro; Kuwahara, Tomohiro; Kai, Nobuyuki; Kikukawa, Hiroaki; Ueda, Shoichi.

In: Cancer chemotherapy and pharmacology, Vol. 61, No. 1, 01.01.2008, p. 53-61.

Research output: Contribution to journalArticle

Wada, Y, Kikuchi, K, Takahashi, W, Honda, J, Nakanishi, J, Matsumoto, K, Kuwahara, T, Kai, N, Kikukawa, H & Ueda, S 2008, 'Docetaxel, low-dose estramustine, and doxifluridine in hormone-refractory metastatic prostate cancer', Cancer chemotherapy and pharmacology, vol. 61, no. 1, pp. 53-61. https://doi.org/10.1007/s00280-007-0445-4
Wada, Yoshihiro ; Kikuchi, Ken ; Takahashi, Wataru ; Honda, Jiro ; Nakanishi, Juro ; Matsumoto, Koichiro ; Kuwahara, Tomohiro ; Kai, Nobuyuki ; Kikukawa, Hiroaki ; Ueda, Shoichi. / Docetaxel, low-dose estramustine, and doxifluridine in hormone-refractory metastatic prostate cancer. In: Cancer chemotherapy and pharmacology. 2008 ; Vol. 61, No. 1. pp. 53-61.
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abstract = "Purpose: Advanced prostate cancer, which is one of the most common cancers, usually progresses to hormone-refractory prostate cancer (HRPC). A recent randomized trial of treatment with docetaxel demonstrated improved survival for patients with HRPC. The combination of docetaxel and estramustine phosphate (estramustine) has been reported to be effective for HRPC. Low-dose estramustine suppresses the pituitary-gonadal axis. Docetaxel plus 5-fluoro-5′- deoxyuridine (5′-dFUrd) had supra-additive cytotoxic effects on HRPC cells consistent with the molecular mechanism. Therefore, we examined the efficacy of adding 5′-dFUrd on the chemotherapy regimen, which consist docetaxel and estramustine. Methods: All of the HRPC patients were treated with estramustine 140 mg orally twice 5′-dFUrd 200 mg orally four times daily on days 1-21, and docetaxel 60 mg/m2 was administered on day 1. We evaluated serum prostate-specific antigen (PSA) and measurable responses, the progression-free and overall survival, and the impact on adverse effects and the quality of life (QOL). Results: Of 34 patients with a median age of 72.3 years, 73{\%} showed PSA responses and 70{\%} showed measurable responses. The median progression-free survival was 18.0 and 5.8 months for PSA responders and non-responders and the overall survival was 19.4 months, respectively. There were few serious adverse effects. Grade 3/4 neutropenia occurred in 32.4{\%} of the patients, and was easily managed with granulocyte colony-stimulating factor (G-CSF) injection. There was no significant change in the overall QOL scores serially. Conclusions: This study shows that the combined regimen is tolerable and effective in Japanese HRPC patients.",
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AU - Wada, Yoshihiro

AU - Kikuchi, Ken

AU - Takahashi, Wataru

AU - Honda, Jiro

AU - Nakanishi, Juro

AU - Matsumoto, Koichiro

AU - Kuwahara, Tomohiro

AU - Kai, Nobuyuki

AU - Kikukawa, Hiroaki

AU - Ueda, Shoichi

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N2 - Purpose: Advanced prostate cancer, which is one of the most common cancers, usually progresses to hormone-refractory prostate cancer (HRPC). A recent randomized trial of treatment with docetaxel demonstrated improved survival for patients with HRPC. The combination of docetaxel and estramustine phosphate (estramustine) has been reported to be effective for HRPC. Low-dose estramustine suppresses the pituitary-gonadal axis. Docetaxel plus 5-fluoro-5′- deoxyuridine (5′-dFUrd) had supra-additive cytotoxic effects on HRPC cells consistent with the molecular mechanism. Therefore, we examined the efficacy of adding 5′-dFUrd on the chemotherapy regimen, which consist docetaxel and estramustine. Methods: All of the HRPC patients were treated with estramustine 140 mg orally twice 5′-dFUrd 200 mg orally four times daily on days 1-21, and docetaxel 60 mg/m2 was administered on day 1. We evaluated serum prostate-specific antigen (PSA) and measurable responses, the progression-free and overall survival, and the impact on adverse effects and the quality of life (QOL). Results: Of 34 patients with a median age of 72.3 years, 73% showed PSA responses and 70% showed measurable responses. The median progression-free survival was 18.0 and 5.8 months for PSA responders and non-responders and the overall survival was 19.4 months, respectively. There were few serious adverse effects. Grade 3/4 neutropenia occurred in 32.4% of the patients, and was easily managed with granulocyte colony-stimulating factor (G-CSF) injection. There was no significant change in the overall QOL scores serially. Conclusions: This study shows that the combined regimen is tolerable and effective in Japanese HRPC patients.

AB - Purpose: Advanced prostate cancer, which is one of the most common cancers, usually progresses to hormone-refractory prostate cancer (HRPC). A recent randomized trial of treatment with docetaxel demonstrated improved survival for patients with HRPC. The combination of docetaxel and estramustine phosphate (estramustine) has been reported to be effective for HRPC. Low-dose estramustine suppresses the pituitary-gonadal axis. Docetaxel plus 5-fluoro-5′- deoxyuridine (5′-dFUrd) had supra-additive cytotoxic effects on HRPC cells consistent with the molecular mechanism. Therefore, we examined the efficacy of adding 5′-dFUrd on the chemotherapy regimen, which consist docetaxel and estramustine. Methods: All of the HRPC patients were treated with estramustine 140 mg orally twice 5′-dFUrd 200 mg orally four times daily on days 1-21, and docetaxel 60 mg/m2 was administered on day 1. We evaluated serum prostate-specific antigen (PSA) and measurable responses, the progression-free and overall survival, and the impact on adverse effects and the quality of life (QOL). Results: Of 34 patients with a median age of 72.3 years, 73% showed PSA responses and 70% showed measurable responses. The median progression-free survival was 18.0 and 5.8 months for PSA responders and non-responders and the overall survival was 19.4 months, respectively. There were few serious adverse effects. Grade 3/4 neutropenia occurred in 32.4% of the patients, and was easily managed with granulocyte colony-stimulating factor (G-CSF) injection. There was no significant change in the overall QOL scores serially. Conclusions: This study shows that the combined regimen is tolerable and effective in Japanese HRPC patients.

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