s-1-(combination) and Prostatic-Neoplasms

5-FU is a major anti-tumor agent, and many clinical trials have been conducted to determine the efficacy of 5-FU and fluoropyrimidine derivatives for the treatment of urological cancers. S-1 is an oral fluoropyrimidine derivative that should be tested to demonstrate clinical efficacy for the treatment of urological cancers. Two phase II trials are being conducted to evaluate the efficacy and safety of S-1 as a single agent therapy for patients with hormone-refractory prostate cancer (HRPC) and renal cell carcinoma (RCC).

Topics: Antimetabolites, Antineoplastic; Carcinoma, Renal Cell; Clinical Trials, Phase II as Topic; Drug Administration Schedule; Drug Combinations; Female; Humans; Kidney Neoplasms; Male; Oxonic Acid; Prostatic Neoplasms; Tegafur; Urologic Neoplasms

This study was conducted to evaluate the efficacy and safety of S-1, an oral fluoropyrimidine derivative, in Japanese patients with castration-resistant prostate cancer (CRPC). The primary endpoint was prostate-specific antigen (PSA) response.. In this open-label phase II study, S-1 was started at a dose of 80, 100 or 120 mg daily based on body surface area (BSA) for 28 days, followed by 14 days of rest. Patients with histological proof of prostate cancer refractory to hormonal therapies were eligible. Patients who received prior chemotherapy were excluded. All patients provided written informed consent. To observe 20% confirmed PSA response, 33 assessable patients were needed. Treatment was continued until disease progression or the development of intolerable toxicity.. A total of 35 eligible patients were enrolled. The median number of treatment cycles was 3. PSA response was observed in 8 patients (22.9%, 90% CI 11.9-37.5), including 3 in which (8.6%) the PSA level normalized. The median overall survival was 25.4 months. The most common treatment-related grade 3 toxicity was anorexia (14.3%). There was no death during the study.. S-1 monotherapy is active against castration-resistant prostate cancer and has acceptable toxicity.

Topics: Adult; Aged; Alanine Transaminase; Androgen Antagonists; Anorexia; Antimetabolites, Antineoplastic; Aspartate Aminotransferases; Bilirubin; Body Surface Area; Dose-Response Relationship, Drug; Drug Combinations; Drug Tolerance; Humans; Lymphatic Metastasis; Male; Middle Aged; Orchiectomy; Oxonic Acid; Prostate-Specific Antigen; Prostatic Neoplasms; Safety; Tegafur; Treatment Outcome

S-1 is a recently developed dihydropyrimidine dehydrogenase inhibitor fluoropyrimidine and has demonstrated high maximum plasma 5-Fluorouracil (5-FU) levels with mild toxicity, and an oral formulation has resulted in an improvement in patient quality of life. The aims of the present study were to determine the efficacy of S-1 or S-1 combined with docetaxel (DOC) using castration resistant prostate cancer (CRPC) cells and to explore their clinical potential for treating CRPC patients. LNCaP cells, androgen dependent prostate cancer (ADPC) cells and C4-2 cells, which are a CRPC subline of LNCaP cells, were used. Specimens obtained from ADPC and CRPC patients were also evaluated. The CRPC specimens and C4-2 cells exhibited significantly lower thymidylate synthase (TS) expression, a target of 5-FU, than the ADPC specimens and LNCaP cells. In vitro, C4-2 cells exhibited higher sensitivity to 5-FU than LNCaP cells. In C4-2 xenograft model, S-1 monotherapy suppressed tumor growth and low-dose DOC enhanced the anti-tumor effect of S-1. In vitro, low-dose DOC, which did not induce G2/M arrest, increased p53 and p21 and resulted in down-regulation of TS in C4-2 cells, and down-regulation of TS is considered to be responsible for the synergistic effect of S-1 in vivo. The present findings indicate that CRPC patients with androgen ablation may be good candidates for 5-FU based chemotherapy, and these regimens have attractive therapeutic potential for clinical practice, and they may have a significant impact on therapeutic options.

Topics: Aged; Animals; Antineoplastic Combined Chemotherapy Protocols; Cell Line, Tumor; Docetaxel; Drug Combinations; Drug Synergism; Fluorouracil; Humans; Ki-67 Antigen; Male; Mice; Mice, SCID; Oxonic Acid; Prostatectomy; Prostatic Neoplasms; Taxoids; Tegafur; Thymidylate Synthase; Xenograft Model Antitumor Assays

Topics: Administration, Oral; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Estramustine; Humans; Male; Oxonic Acid; Prostatic Neoplasms; Tegafur; Uracil