s-1-(combination) and Urinary-Bladder-Neoplasms

A 67-year-old man with bladder cancer who was treated with transurethral resection of bladder tumour(TUR-Bt)and chemotherapy at the age of 59 years was diagnosed as having urothelial cancer by biopsy 8 years later. Detailed examination revealed the presence of synchronous triple cancer, with hepatocellular cancer and gastric cancer. Subsequently, semi-total gastrectomy, partial hepatectomy(S6), radio frequency ablation(S5, S7), and cholecystectomy were performed. Histologically, the gastric tumor was a moderately differentiated tubular adenocarcinoma, the hepatic tumor was a moderately differentiated hepatocellular carcinoma, the bladder tumor was a transitional cell carcinoma, and the ureteral tumor was an urothelial carcinoma.

Topics: Aged; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Drug Combinations; Humans; Liver Neoplasms; Male; Neoplasms, Multiple Primary; Oxonic Acid; Stomach Neoplasms; Tegafur; Treatment Outcome; Urinary Bladder Neoplasms; Urologic Neoplasms

A 67-year-old woman presented with macroscopic hematuria and lower abdominal pain. Cystoscopy revealed a broad-stalk non-papillary tumor at the bladder dome. Computed tomography (CT) showed a tumor extending from the umbilicus to the bladder dome, together with multiple lung metastases. Serum carcinoembryonic antigen and cancer antigen (CA19-9) levels were elevated at 7.0 ng/ml and 180 U/ml, respectively. Transurethral resection of the tumor was performed and histopathology revealed adenocarcinoma. Therefore, the tumor was diagnosed as a stage IVB (Sheldon's category) urachal carcinoma. En bloc segmental resection of the urachal carcinoma with the bladder dome was performed, followed by chemotherapy with tegafur, gimestat, and otastat potassium (TS-1) and cisplatin. The disease remained stable for 8 months. However, a follow up CT scan after 11 chemotherapy cycles showed progression of the lung metastases. In spite of the change to a second-line gemcitabine and cisplatin chemotherapy regimen, the disease continued to progress after 4 cycles.

Topics: Adenocarcinoma; Aged; Antigens, Tumor-Associated, Carbohydrate; Antineoplastic Combined Chemotherapy Protocols; Carcinoembryonic Antigen; Drug Combinations; Female; Humans; Lung Neoplasms; Oxonic Acid; Tegafur; Urinary Bladder Neoplasms

Thymidylate synthase (TS), a target enzyme of 5-fluorouracil (5-FU), is significantly associated with prognosis in various cancers. Recently, it has been reported that S-1, a novel 5-FU-based agent has an effect on bladder cancer. However, in cells with high TS level, S-1 did not have significant effects. Therefore, we examined whether down-regulation of TS enhanced effects of S-1 in them. First, we measured TS level in an aggressive bladder cancer cell line, KU-19-19 by enzyme-linked immunosorbent assay (ELISA) and evaluated its sensitivity to 5-FU using a small interfering RNA (siRNA) for TS. Next, we measured TS mRNA after exposure to various agents. Finally, we evaluated enhancement of cytotoxicity of S-1 by CPT-11 (7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin) which down-regulated TS in in vivo study. The median TS and dihydropyrimidine dehydrogenase (DPD) level was 53.3 ng/mg and 80.3 ng/mg in KU-19-19 cells, respectively. The 5-FU treatment in KU-19-19 cells transfected with siRNA for TS gene (TYMS) inhibited cell growth more significantly than that for nontargeting control. Down-regulation of TS was observed after exposure to SN-38 (7-ethyl-10-hydroxycamptothecin) in a dose-dependent manner. The combination treatment of 5-FU and SN-38 significantly inhibited cell growth, as compared to the single treatment. Meanwhile, in cells transfected with siRNA for TYMS, neither an additive nor a synergistic effect was observed. Also, combined S-1 and CPT-11 dramatically inhibited tumor growth, compared to S-1 or CPT-11 alone in in vivo study. In conclusion, CPT-11 down-regulated TS level and enhanced the effect of S-1. Thus, the combination therapy with S-1 and CPT-11 might be a novel modality for bladder cancer, even with high TS level.

Topics: Animals; Camptothecin; Cell Line, Tumor; Disease Models, Animal; Dose-Response Relationship, Drug; Down-Regulation; Drug Combinations; Drug Resistance, Neoplasm; Drug Synergism; Female; Gene Expression Regulation, Neoplastic; Humans; Irinotecan; Mice; Mice, Nude; Oxonic Acid; RNA Interference; RNA, Small Interfering; Tegafur; Thymidylate Synthase; Urinary Bladder Neoplasms; Xenograft Model Antitumor Assays

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Docetaxel; Drug Combinations; Drug Resistance, Neoplasm; Humans; Lung Neoplasms; Lymphatic Metastasis; Male; Oxonic Acid; Paget Disease, Extramammary; Skin Neoplasms; Taxoids; Tegafur; Tomography, X-Ray Computed; Urinary Bladder Neoplasms

A 70-year-old male visited the hospital with a complaint of stomachache. Hydronephrosis was observed in the right kidney, and further examination confirmed a diagnosis of metastatic cancer limited to the bladder and rectovesical pouch after surgery for differentiated gastric cancer. Chemotherapy using paclitaxel(PTX)/S-1 was initiated. One course included 14 days of administration of S-1 (100 mg/body) followed by a 7-day interval, and the administration of PTX (60 mg/body) on the 1st and 15th days. General malaise developed after 4 courses, the dose of S-1 was reduced (80 mg/body), and PTX was administered only on the 1st day. CT conducted 9 months after the start of chemotherapy revealed the disappearance of ascites, decreased thickness of the bladder wall, and reduced size of the tumor in the rectovesical pouch. No new distal metastasis or peritoneal metastatic nodule has been observed, and there has been no tendency toward exacerbation for one year after the initial diagnosis. PTX/S-1 was suggested to be an effective treatment for metastatic cancer limited to the bladder and rectovesical pouch after surgery for differentiated gastric cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cell Differentiation; Drug Combinations; Humans; Male; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Tegafur; Tomography, X-Ray Computed; Urinary Bladder Neoplasms

No established treatment exists for urachal carcinoma,except curative resection,and its prognosis is poor. More than 80% of urachal carcinomas are adenocarcinomas. We report a case of advanced urachal carcinoma treated with S-1 and cisplatin combination (S-1/CDDP) chemotherapy. The patient,a 61-year-old woman,presented with macroscopic hematuria. A tumor was detected on the bladder dome and transurethral resection was performed. Histopathological findings indicated poorly differentiated adenocarcinoma. Serum carcinoembryonic antigen and carbohydrate antigen 19-9 levels were 3.5 ng/ml and 140 U/ml respectively. Magnetic resonance images indicated an extension of this tumor to the retroperioneal space. Metastasis to her right ischium was suspected from bone scintigraphy results. The tumor was diagnosed as stage IVB (Sheldon's category) urachal carcinoma. After one cycle of S-1/CDDP chemotherapy,the size of the tumor on the bladder dome decreased,after which total cystectomy was performed. The surgical margin of the cystectomy specimen was negative for malignant cells,although poorly differentiated adenocarcinoma was still observed in this specimen. The findings of this study indicate that this therapy might be beneficial for treating advanced urachal carcinomas. This is the second report of successful treatment of advanced urachal carcinoma with S-1/CDDP chemotherapy.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Cystectomy; Drug Combinations; Female; Humans; Middle Aged; Oxonic Acid; Tegafur; Urachus; Urinary Bladder Neoplasms

A 77-year-old man was admitted to our hospital complaining of general malaise, loss of appetite and hemoptysis. Chest X-ray film and computed tomography (CT) scan showed right-sided pleural effusion with lung tumor. Succeeding upper gastro-intestinal fiberscopy and cystoscopy revealed poorly-differentiated adenocarcinoma of the stomach and urothelial carcinoma of the bladder. Repeated treatment with 100 mg/body of S-1 on day 1 followed by 60 mg/m(2) of cisplatin on day 8 was effective in this patient.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Gastroscopy; Humans; Lung Neoplasms; Magnetic Resonance Imaging; Male; Neoplasm Staging; Neoplasms, Multiple Primary; Oxonic Acid; Stomach Neoplasms; Tegafur; Tomography, X-Ray Computed; Urinary Bladder Neoplasms

We report a case of recurrent advanced urachal carcinoma with right internal iliac node and left lung metastases in a 34-year-old man. After receiving partial cystectomy including en bloc resection of the urachus and with bilateral pelvic lymph node dissection, he was treated with five courses of S-1 and cisplatin combination chemotherapy. He remains free from the disease after a 30-month follow-up period. S-1/cisplatin combination chemotherapy is suggested to be a potent tool for controlling advanced urachal carcinoma.

Topics: Adenocarcinoma; Adult; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Hematuria; Humans; Iliac Artery; Lung Neoplasms; Lymph Node Excision; Lymphatic Metastasis; Male; Oxonic Acid; Tegafur; Urachus; Urinary Bladder Neoplasms