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Chikara Ohyama

Publications and source records attributed to Chikara Ohyama.

At least 19 recordsLinked to original sources

N-acetylglucosaminyltransferase V and beta1-6 branching N-linked oligosaccharides are associated with good prognosis of patients with bladder cancer.

PURPOSE: N-acetylglucosaminyltransferase V (GnT-V) is an enzyme that catalyzes beta1-6 branching of N-acetylglucosamine on asparagine (N)-linked oligosaccharides (N-glycan) of cell proteins. We examined the relationship between GnT-V expression and clinicopathologic features of the patients with bladder cancer. EXPERIMENTAL DESIGN: We immunohistochemically examined GnT-V expression in paraffin-embedded bladder cancer specimen using anti-GnT-V monoclonal antibody. We compared GnT-V expression with cause-specific survival of the patients with bladder cancer treated by radical cystectomy. Kaplan-Meier survival curves were generated to show the cause-specific survival. Univariate and multivariate analyses were carried out to compare GnT-V expression with other clinical and pathologic variables. We also evaluated mRNA expression of GnT-V and N-linked oligosaccharide structure in bladder cancer specimens. RESULTS: Immunohistochemistry revealed that GnT-V expression inversely correlated with tumor grade and stage. The incidence of positive GnT-V expression in bladder cancer was significantly higher in low-grade/superficial cancer than in high-grade/invasive cancer. The patients whose tumor was positive for GnT-V survived significantly longer than those whose tumor was negative for GnT-V. Univariate and multivariate analyses revealed that GnT-V expression was an independent predictor of prognosis of the patient. The expression of GnT-V mRNA determined by reverse transcription-PCR was consistent with the results with immunohistochemistry for tumor samples. Carbohydrate structural analysis revealed that superficial bladder cancer is rich in branched N-linked oligosaccharides, for which biosynthesis GnT-V is responsible. CONCLUSIONS: GnT-V and its resultant beta1-6 branching N-linked oligosaccharides are closely related to low malignant potential and good prognosis of the patients with bladder cancer.

Adult↗

A randomized comparative study of endocrine monotherapy and a combination of estramustine phosphate with the endocrine therapy in patients with untreated stage D prostate cancer.

BACKGROUND: We investigated the clinical efficacy and the prolongation of survival with combination therapy of estramustine phosphate (EMP) and endocrine therapy in untreated patients with progressive prostate cancer. METHODS: We randomly divided 57 patients with untreated stage D prostate cancer into two groups, an endocrine monotherapy group and a group receiving combination treatment, consisting of endocrine therapy plus EMP. Treatment was continued until deterioration. RESULTS: There were no significant differences in the improvement rating for subjective/objective symptoms or in progression-free survival between the two groups. However, overall survival was significantly prolonged in the combination therapy group (log-rank test, P = 0.0394; generalized Wilcoxon's test, P = 0.0145). In particular, overall survival was significantly prolonged, compared to that in the endocrine monotherapy group, in patients in the combination therapy group who were less than 74 years old, those with a performance status (PS) of 1 to 3, a pretreatment prostate-specific antigen (PSA) level of more than 20 ng/ml, moderately or poorly differentiated carcinoma, or a partial response (PR) based on the PSA level 12 weeks after the start of treatment. There was no significant difference in the incidence of side effects between the combination therapy and the endocrine monotherapy groups. CONCLUSION: A combination of EMP with endocrine therapy may be useful for initial treatment in younger patients (aged 73 or younger) and in patients at high risk of progressive prostate cancer.

Aged↗

Predictive value of N-acetylglucosaminyltransferase-V for superficial bladder cancer recurrence.

PURPOSE: GnT-V is an enzyme that catalyzes beta1-6 branching of N-acetylglucosamine on asparagine (N)-linked oligosaccharides of cell proteins. GnT-V expression has been closely related to malignant potentials in colon cancer, brain cancer and hepatocellular carcinoma. We determined whether GnT-V expression is predictive of superficial bladder cancer recurrence. MATERIALS AND METHODS: The cohort comprised 60 consecutive patients with first time superficial bladder cancer treated with transurethral resection. None of the patients received prophylactic intravesical therapy until recurrence. Paraffin embedded tumor specimens were immunohistochemically examined by the avidin-biotin peroxidase method using monoclonal antibody against GnT-V. Kaplan-Meier survival curves were generated to determine disease-free survival. Univariate and multivariate analyses were done to compare GnT-V expression to other clinical and pathological variables. RESULTS: GnT-V expression correlated inversely with tumor grade and stage. The positive incidence of GnT-V in G1 to G3 tumors was 7 of 9 (78%), 21 of 43 (49%) and 3 of 8 (38%), respectively. GnT-V was positive in 26 of 44 cases of pTa (60%) and in 5 of 16 of pT1 (31%) disease. The 31 patients with positive GnT-V expression had significantly higher disease-free survival than the 29 with negative GnT-V expression (log rank test p = 0.0034). Multivariate analysis revealed that patient age, pT, grade and negative GnT-V expression were independent predictors of recurrence (p = 0.015, 0.001, 0.019 and 0.011, respectively). CONCLUSIONS: Immunohistochemical detection of GnT-V is an independent predictor of superficial bladder cancer recurrence.

Aged↗

Experience and functional outcome of modified ileal neobladder in 95 patients.

AIMS: We took advantage of the Goodwin method to develop a modified ileal neobladder. We present the operation procedure and assessed the functional results. METHODS: From April 1997 and May 2005, 95 patients (75 men and 20 women), mean age 64.6 years (range: 36-80 years) underwent orthotopic ileal neobladder replacement with application of the Goodwin method. The Le Duc technique was used for antireflux procedure. However, for the last 35 patients, antireflux procedure was not carried out. The median follow-up period was 37 months (range: 3-98 months). We reviewed the surgical outcome and complications. Continent status and urodynamic profile were also measured. RESULTS: The mean operation time for the neobladder formation was 130 mins (range: 65-285 mins). There were no perioperative deaths. Leakage from the ileourethral anastomosis leak was found in four patients (4.2%), wound infection in nine patients (9.5%), ileal anastomosis leak in two patients (2.1%) and paralytic ileus in two patients. No hydronephrosis, neobladder-ureteral reflux or deterioration of renal function was seen. The maximum neobladder pressure was 21 +/- 13 cm (mean +/- SD) at 6 months and 12 +/- 11 cm at 12 months after surgery. The neobladder capacity was 293 +/- 118 mL at 6 months and 312 +/- 85 mL at 12 months after surgery. Of the 95 patients, 87 (91.6%) maintained complete dryness day and night. CONCLUSIONS: These results suggest that the present orthotopic ileal neobladder is simple to be carried out and achieves acceptable voiding function. Longer observation for neobladder and upper urinary tract function is necessary.

Adult↗

An A/G polymorphism of core 2 branching enzyme gene is associated with prostate cancer.

The expression of core 2 beta1,6-N-acetylglucosaminyltransferase-1 (C2GnT) is associated with development and progression of malignancy. Sequence analysis showed that the codon 152 of C2GnT has a polymorphism having GTT encoding valine or ATT encoding isoleucine. By examining the polymorphism in prostate cancer and benign prostatic hyperplasia patients, we found that the C2GnT G allele was more frequently observed in the prostate cancer group (p=0.015) than the control group. Men with the GG genotype had a 3.60-fold increased risk of prostate cancer, and men with the AG genotype had a 1.58-fold increased risk of prostate cancer compared with those with the AA genotype. The G allele was found to have a gene dosage effect for prostate cancer risk. No such risk was associated for benign prostatic hyperplasia. These results demonstrate that C2GnT A/G polymorphism is associated with the susceptibility to prostate cancer in a Japanese population.

1,4-alpha-Glucan Branching Enzyme↗

Expression of core 2 beta1,6-N-acetylglucosaminyltransferase facilitates prostate cancer progression.

Cell surface carbohydrates expressed on epithelial cells are thought to play an important role in tumor progression. Previously, we have shown that expression of core 2-branched O-glycans is closely correlated with vessel invasion and depth of invasion in colon and lung carcinomas. In this study, we found that expression of core 2 beta1,6-N-acetylglucosaminyltransferase-1, Core2GnT, is positively correlated with the progression of prostate cancer in human patients. Statistical analysis demonstrated that Core2GnT is an independent predictor for progressed pathological stage (pT3) and for prostate-specific antigen (PSA) relapse. To determine directly the roles of Core2GnT in prostate cancer progression, we set up an experimental tumor model using the LNCaP prostate cancer cell line. Because this line does not express Core2GnT, we established an LNCaP line stably expressing Core2GnT, LNCap-Core2GnT, by transfecting cDNA encoding Core2GnT. When mock-transfected LNCaP cells and LNCaP-Core2GnT were inoculated in the prostate of nude mice, LNCaP-Core2GnT cells produced three times heavier prostate tumors than mock-transfected LNCaP cells. Furthermore, we found that LNCaP-Core2GnT cells adhered more strongly to prostate stromal cells, type IV collagen and laminin than did LNCaP-mock cells, but LNCaP and LNCaP-Core2GnT cells grew almost at the same rate on plates coated with type IV collagen or laminin. These results indicate that Core2GnT is an extremely useful prognostic marker for prostate cancer progression. The results also suggest that acquiring Core2GnT in prostate carcinoma cells facilitates adhesion to type IV collagen and laminin, and this increased adhesion may be a cause for aggressive tumor formation by prostate cancer cells expressing Core2GnT.

Aged↗

Intraoperative, radio-guided sentinel lymph node mapping in laparoscopic lymph node dissection for Stage I testicular carcinoma.

BACKGROUND: The management of regional lymph nodes in patients with clinical Stage I testicular carcinoma is a controversial problem. The authors investigated the feasibility and accuracy of radio-guided mapping of sentinel lymph nodes (SLNs) for men with clinical Stage I testicular tumors. METHODS: Twenty-two patients with clinical Stage I testicular carcinoma were enrolled in the study. One day before surgery, (99m)Technetium-labeled phytate was injected around the testicular tumor. After undergoing radical orchiectomy, patients underwent laparoscopic retroperitoneal lymph node dissection (L-RPLND). All radioactive lymph nodes were marked in the L-RPLND procedure, and three-dimensional SLN maps were made. All resected lymph nodes were evaluated by routine histopathologic examination, and the clinical significance of intraoperative SLN mapping was evaluated. RESULTS: SLNs were detected in 21 of 22 patients (95%). Nearly all SLNs were detected at the ventral or lateral side of the vena cava or at the aorta between the levels of the aortic bifurcation. All SLNs were detected easily in a surgical procedure. Only 1 radio-positive area per patient was identified in 15 patients, and approximately 2-4 positive areas were detected in 6 patients. Two patients had micrometastasis only in SLNs. In 2 patients who had seminoma, lymph node recurrences (at the level of the renal vein and in the obturator lymph node area) occurred at 10 months and 20 months after surgery. CONCLUSIONS: Radio-guided mapping of SLNs with laparoscopy was feasible, and nearly all SLNs were detected accurately by the procedure. In the near future, the standard retroperitoneal lymph node dissection may be avoided in most patients with clinical Stage I testicular carcinoma by utilizing focused examination of SLNs.

Adult↗

Activation of natural killer T cells by alpha-galactosylceramide mediates clearance of bacteria in murine urinary tract infection.

PURPOSE: alpha-Galactosylceramide (alpha-GalCer), which is a specific ligand for CD1d restricted variable-alpha14chain natural killer T cells, has an important role in host defense against a range of microbial infections. We examined whether alpha-GalCer mediates bacterial clearance in a murine urinary tract infection (UTI) model. MATERIALS AND METHODS: The murine UTI model was established by intravesical inoculation of Escherichia coli, Pseudomonas aeruginosa or methicillin resistant Staphylococcus aureus, followed by clamping the distal end of the urethra of C57BL/6 female mice for 4 hours. The antibacterial effect of alpha-GalCer was assessed by comparing the number of cfu/gm kidney tissue 4 days after bacterial inoculation. The prophylactic effect of alpha-GalCer was examined by administrating 3 doses of intraperitoneal alpha-GalCer on alternate days 24 hours before E. coli inoculation. The therapeutic effect of alpha-GalCer was tested by the administration of 2 doses of intraperitoneal alpha-GalCer after bacterial inoculation. To assess cytokine induction by alpha-GalCer serum levels of interleukin-12, interferon-gamma and tumor necrosis factor-alpha were measured by cytometric bead array assay. RESULTS: When administered before bacterial inoculation, alpha-GalCer showed a strong prophylactic antibacterial effect. alpha-GalCer also showed a marked antibacterial effect on preestablished mice UTI caused by E. coli, P. aeruginosa and methicillin resistant S. aureus. alpha-GalCer induced a significantly higher level of interleukin-12, interferon-gamma and tumor necrosis factor-alpha compared with control glycolipids. CONCLUSIONS: These findings suggest a significant role for alpha-GalCer in regulating antibacterial functions by activating natural killer T cells in the murine UTI model.

Animals↗

Successful renal transplantation in the right iliac fossa 2 years after serious deep venous thrombosis in a patient with systemic lupus erythematosus.

Deep venous thrombosis (DVT) possibly occurs in the perioperative period, and induces serious complications such as a pulmonary embolism. On the other hand, allograft renal vein thrombosis leads to a high incidence of graft loss. We experienced a case in which a serious DVT occurred prior to renal transplantation; however, a successful renal transplantation in the right iliac fossa was performed after 2 years of anticoagulant therapy. It is suggested that the external iliac vein even after suffering from DVT can be anastomosed to an allograft vein successfully, when enough blood fl ow or a lower venous pressure is confirmed. However, one should be aware of the risk factors and the adequate management of thrombosis in renal transplantation because of the serious complications of DVT and the poor prognosis of allograft vein thrombosis.

Adult↗

[Tumor markers in prostate cancer--clinical significance and future prospect of prostate specific antigen (PSA)].

Prostate specific antigen (PSA), which has high organ specificity, is an excellent tumor marker that has played a significant role in the diagnosis and treatment of prostate cancer. Screening for prostate cancer using PSA is now widely employed in Japan, and increased detection of cases with organ-confined prostate cancer is hoped to result in a decreased number of cancer-specific deaths. Although PSA has also played a critical role in as a marker for staging, assessment of treatment, and recurrence of prostate cancer, many useless biopsies are performed due to its low cancer specificity. To increase the specificity in prostate cancer detection, PSA-related markers including PSAD (PSAPZD), PSAV, and age-specific PSA were advocated, and the ratio of free PSA to total PSA (% free PSA) is also used in a clinical setting. However, since those markers can not satisfactorily exclude benign prostate diseases, various molecular forms of PSA have been analyzed using proteomics and glycomics. Recently, it was demonstrated that plasma free PSA consisted of precursor PSA (pPSA) and other isoforms, suggesting that [-2] pPSA may be a helpful marker for prostate cancer. Our group reported that a sugar chain structure of PSA in the serum of prostate cancer patients is different from that of patients with benign prostate hyperplasia. The different sugar chain structure of PSA can be easily detected by a conventional method and is expected to be useful for differential diagnosis between malignant and benign prostate diseases.

Biomarkers, Tumor↗

[Active combination immunochemotherapy with interferon-alpha, interleukin-2 and gemcitabine for four patients with metastatic renal cell carcinoma].

Immunochemotherapy consisting of interferon-alpha (IFN-alpha), interleukin-2 (IL-2), and gemcitabine (GEM) for metastatic renal cell carcinoma. A partial response maintained for 15 months, was obtained in one case resistant to IFN-alpha and IL-2 of para-aortic lymph node metastases (case 1). A minor response with 30% reduction of lung metastasis was obtained in one IFN-alpha resistant case, and the duration was 6 months (case 2). In one case, in contra-lateral renal metastasis, no disease progression was obtained for 6 months (case 3). One case with resistance to IFN-alpha and IL-2, and who had preoperative abnormalities of corrected serum calcium, serum c-reactive protein and hemoglobin, had progressive disease and died of cancer after 6 months (case 4). Grade 3 toxicity was noted in leucopenia (4/4), anemia (1/4), and nausea/ vomiting (1/4). Although the response duration was short, the combination immunochemotherapy consisting of IFN-alpha, IL-2 and GEM may be a promising salvage regimen for the patients with metastatic renal cell carcinoma.

Adult↗

[A case of fibroepithelial polyp of the ureter resected ureteroscopically].

A case of a giant fibroepithelial polyp of the ureter is presented. A 76-year-old woman was pointed out to have a tumorus lesion in the urinary bladder by ultrasonography. Intravenous pyelography showed a filling defect in the lower portion of the left ureter and bladder. Cystoscopy revealed a tumor with a smooth surface sticking out of the left ureteral orifice. After demonstration of benign ureteral polyp without malignancy by biopsy, ureteroscopic resection was performed. The stalk of the polyp was coagulated and removed with biopsy forceps under ureteroscopy. Pathological diagnosis was a fibroepithelial polyp. There were no findings of polyp recurrence or ureteral stenosis at 9 months after the operation. The diagnosis and management of fibroepithelial polyp are discussed.

Aged↗

[A case of giant epidermoid cyst occupying the testis].

A case of a giant epidermoid cyst of the testis is presented. A 65-year-old man was incidentally pointed out to have left scrotal painless swelling. Physical examination revealed an over hen-egg sized enlargement of the left scrotal contents. Ultrasonography revealed a 7.5 X 5.5 X 4.0 cm solid tumor with heterogeneous echogenicity. No other abnormal findings were observed including tumor markers. Since preoperative examination did not rule out malignancy, we performed left high orchiectomy. Pathological diagnosis was a epidermoid cyst of the testis with a small portion of atrophic testis. Although the preoperative diagnosis of testicular epidermoid cyst is possible, it may be considerably difficult when a giant epidermoid cyst is occupying the testis.

Aged↗

Association of lipoprotein lipase gene polymorphism with risk of prostate cancer in a Japanese population.

A high fat intake has been associated with prostate cancer risk, and gene polymorphisms of lipoprotein lipase (LPL) play an important role in plasma lipoprotein metabolism. We herein analyzed the association of LPL gene polymorphisms with the risk of prostate cancer in a Japanese population. Three single nucleotide polymorphisms (SNPs) of LPL designated as Ser447stop, HindIII and PvuII were genotyped by the polymerase chain reaction-restriction fragment length polymorphism method in 273 prostate cancer patients, 205 benign prostatic hyperplasia (BPH) patients and 230 male controls. The men with the CG + GG genotypes of the Ser447stop polymorphism had an increased risk of prostate cancer compared to those with the CC genotype [age-adjusted odds ratio (aOR) = 1.625; 95% CI = 1.068-2.471; p = 0.023]. Furthermore, the increased risk associated with the CG + GG genotypes was more strongly observed in patients with high-grade cancers (aOR = 2.843; 95% CI = 1.252-6.458; p = 0.039) or metastatic diseases (aOR = 2.300; 95% CI = 1.042-5.074; p = 0.013), whereas the risk was not significant in those with low- to intermediate-grade cancers or nonmetastatic diseases. In the HindIII and PvuII polymorphisms, there was no significant difference between the prostate cancer patients and the controls, and no significant results as for tumor grade and stage. None of the 3 polymorphisms showed any association with the risk of BPH. Our results suggest that the LPL Ser447stop polymorphism is a common genetic modifier for the development of prostate cancer, particularly that of high-grade and/or high-stage, in a Japanese population.

Aged↗

Influence of CYP3A5 and MDR1 (ABCB1) polymorphisms on the pharmacokinetics of tacrolimus in renal transplant recipients.

BACKGROUND: A body-weight-based dose of tacrolimus often results in marked individual diversity of blood drug concentration. Tacrolimus is a substrate for cytochrome P450 (CYP) 3A5 and p-glycoprotein encoded by CYP3A5 and MDR1 (ABCB1), respectively, having multiple single nucleotide polymorphisms. In this study, we genotyped CYP3A5 A6986G, MDR1 G2677(A/T), and C3435T polymorphisms and investigated the association between these polymorphisms and the pharmacokinetics of tacrolimus in renal transplant recipients. METHODS: Thirty consecutive recipients were enrolled in this study. The pharmacokinetics of tacrolimus was analyzed on day 28 after transplant, when the daily dose was adjusted to the target trough level of 10-15 ng/mL. The polymerase chain reaction-restriction fragment length polymorphism and direct sequence method were used for genotyping the CYP3A5 and MDR1 polymorphisms, respectively. RESULTS: The single tacrolimus dose per body weight was significantly higher in CYP3A5 *1 carriers than CYP3A5 *3/*3 carriers (0.143+/-0.050 vs. 0.078+/-0.031 mg/kg, P<0.001). The dose-adjusted trough level and the area under the concentration-time curve (AUC0-12) were significantly lower in CYP3A5 *1 carriers than CYP3A5 *3/*3 carriers (0.040+/-0.014 vs. 0.057+/-0.024 ng/mL/mg/kg, P=0.015 and 0.583+/-0.162 vs. 0.899+/-0.319 ng.hr/mL/mg/kg, P=0.004), respectively. The MDR1 polymorphism was not associated with any pharmacokinetic parameters. CONCLUSIONS: Kidney transplant recipients with the CYP3A5 *1 allele required a higher daily tacrolimus dose compared with those with the CYP3A5 *3/*3 genotype to maintain both the target trough level and AUC0-12, suggesting that this polymorphism is useful for determining the appropriate dose of tacrolimus.

Adult↗

Functional correlation of trophinin expression with the malignancy of testicular germ cell tumor.

Trophinin is a membrane protein that is potentially involved in human embryo implantation by mediating homophillic cell adhesion between trophoblastic cells and endometrial cells. Trophinin expression by maternal cells may be induced by the embryo that secretes human chorionic gonadotropin (hCG). Because the process of tumor metastasis resembles that of trophoblast invasion and proliferation during embryo implantation, we hypothesized that testicular cancers that synthesize hCG express trophinin thus becoming aggressive trophoblast-like cells. We screened paraffin-embedded orchiectomy specimens of 158 patients with testicular germ cell tumor by immunohistochemistry using antitrophinin antibody. This screening identified trophinin-positive specimens with the frequencies 39 of 91 (43%) in stage I, 14 of 24 (58%) in stage II, and 41 of 43 (95%) in stage III (P < 0.001). Thus, trophinin expression positively correlates with clinical stage. Remarkably, trophinin was found in all of the cases (33 of 33) with lung metastasis. The levels of serum hCG-beta were significantly higher in the patients with trophinin-positive tumors than those with trophinin-negative tumors (P = 0.004). To determine whether trophinin promotes aggressiveness of the cell, trophinin-negative human seminona cell line JKT-1 was stably transfected with a mammalian expression vector containing trophinin cDNA. In vitro assays revealed that trophinin-expressing JKT-1-Tro cells are more invasive than JKT-1-mock cells, whereas there are no differences between JKT-1-Tro and JKT-1-mock in their proliferation activity. Upon orthotopic inoculation to athymic nude mice, JKT-1-Tro cells exhibited i.p. metastases in all of the mice (n = 5), whereas JKT-1-mock produced no metastases (n = 5). These results suggest strongly that trophinin enhances invasiveness of the cells and promotes metastasis of testicular germ cell tumor.

Animals↗

Carbohydrate structure and differential binding of prostate specific antigen to Maackia amurensis lectin between prostate cancer and benign prostate hypertrophy.

Serum prostate-specific antigen (PSA) assay is widely used for detection of prostate cancer. Because PSA is also synthesized from normal prostate, false positive diagnosis cannot be avoided by the conventional serum PSA test. To apply the cancer-associated carbohydrate alteration to the improvement of PSA assay, we first elucidated the structures of PSA purified from human seminal fluid. The predominant core structure of N-glycans of seminal fluid PSA was a complex type biantennary oligosaccharide and was consistent with the structure reported previously. However, we found the sialic acid alpha2-3 galactose linkage as an additional terminal carbohydrate structure on seminal fluid PSA. We then analyzed the carbohydrate moiety of serum PSA from the patients with prostate cancer and benign prostate hypertrophy using lectin affinity chromatography. Lectin binding was assessed by lectin affinity column chromatography followed by determining the amount of total and free PSA. Concanavalin A, Lens culinaris, Aleuria aurantia, Sambucus nigra, and Maackia amurensis lectins were tested for their binding to the carbohydrates on PSA. Among the lectins examined, the M. amurensis agglutinin-bound fraction of free serum PSA is increased in prostate cancer patients compared to benign prostate hypertrophy patients. The binding of PSA to M. amurensis agglutinin, which recognizes alpha2,3-linked sialic acid, was also confirmed by surface plasmon resonance analysis. These results suggest that the differential binding of free serum PSA to M. amurensis agglutinin lectin between prostate cancer and benign prostate hypertrophy could be a potential measure for diagnosis of prostate cancer.

Carbohydrates↗

Gemcitabine plus carboplatin; and gemcitabine, docetaxel, and carboplatin combined chemotherapy regimens in patients with metastatic urothelial carcinoma previously treated with a platinum-based regimen: preliminary report.

BACKGROUND: The aim of this study was to evaluate the efficacy and safety of two combined chemotherapy regimens in the treatment of previously treated metastatic urothelial carcinoma: gemcitabine plus carboplatin (GC), and gemcitabine, docetaxel, and carboplatin (GDC). METHODS: Sixteen patients with metastatic urothelial cancer, previously treated with a platinum-based regimen, were studied. GC (gemcitabine 750 mg/m(2), on days 1, 8, and 15; carboplatin 200 mg/m(2), on day 2) was administered every 28 days to 15 patients. GDC (gemcitabine 750 mg/m(2), on days 1 and 8; docetaxel 50 mg/m(2), on day 1; carboplatin 200 mg/m(2) on day 1) was administered every 21 days to 9 patients. Eight of the 9 GDC-treated patients had earlier been treated with GC and had become refractory. RESULTS: With the GC therapy, 7 of the 15 treated patients (47%; 95% confidence interval, 21%-73%) showed an objective response, with 3 achieving a clinical complete response (CR) and 4 a partial response (PR). With the GDC therapy, 6 of the 9 treated patients (67%; 95% confidence interval, 29%-92%) showed an objective response, with 1 achieving CR and 5, PR. Five of the 8 (63%) GC-refractory patients responded to GDC therapy. The median duration of response was 4 months (range, 2-10+ months) on GC therapy, and 3 months (range, 3-5 months) on GDC therapy. Toxicities associated with GC were less than those with GDC. CONCLUSION: GC was effective for refractory metastatic urothelial cancer, and GDC was effective for GC-refractory cancer. The aim of this study was to evaluate the efficacy and safety of two combined chemotherapy regimens in the treatment of previously treated metastatic urothelial carcinoma: gemcitabine plus carboplatin (GC), and gemcitabine, docetaxel, and carboplatin (GDC).

Aged↗