[Show abstract][Hide abstract] ABSTRACT: Single-agent interferon (IFN) is no longer regarded as a standard option for first-line systemic treatment of metastatic renal cell carcinoma (RCC) in Western countries. However, some patients with favorable-risk RCC may still achieve complete and long-lasting remission in response to IFN treatment. The present study compared favorable-risk Japanese patients with metastatic RCC Japanese patients who had been treated with IFN or tyrosine kinase inhibitor (TKI) therapy as a first-line systemic therapy.
From 1995 to 2014, a total of 48 patients with favorable risk as defined by the Memorial Sloan Kettering Cancer Center criteria who did not receive adjuvant systemic therapy were retrospectively enrolled in this study. We assessed the tumor response rate, progression-free survival (PFS), and overall survival (OS).
The objective response rate for first-line therapy was 29% in the IFN group and 47% in the TKI group, but this difference did not reach the level of statistical significance. Median OS for IFN and TKI was 71 and 47 months, respectively (p=0.014). Median first-line PFS for IFN and TKI was 20 and 16 months, respectively (no significant difference). First-line IFN therapy did not prove inferior to TKI therapy in terms of OS according to metastatic sites.
IFN is associated with a survival benefit in Japanese patients with favorable-risk metastatic RCC in the era of targeted therapy. Further prospective study is needed.
Korean journal of urology 03/2015; 56(3):205-11. DOI:10.4111/kju.2015.56.3.205
[Show abstract][Hide abstract] ABSTRACT: Objectives
To investigate the therapeutic outcomes of neoadjuvant and concurrent androgen-deprivation therapy and intensity-modulated radiation therapy with gold marker implantation for intermediate- and high-risk prostate cancer.Methods
This was a retrospective study of 325 patients with intermediate- or high-risk prostate cancer according to the National Comprehensive Cancer Network guidelines who underwent androgen-deprivation therapy and intensity-modulated radiation therapy (76 Gy) after gold marker implantation between 2001 and 2010.ResultsThe 5-year distant metastasis-free survival rate was significantly lower for very high-risk patients than for intermediate- and high-risk patients (82.6% vs 99.4% and 96.5%, respectively; P < 0.01). The 5-year biochemical relapse-free survival rates significantly declined with increasing prostate cancer risk (P < 0.01), and were 95.9%, 87.2%, and 73.1% for the intermediate-risk, high-risk and very high-risk patients, respectively. Acute genitourinary and gastrointestinal toxicity grade ≥3 were not observed in any of the patients. Late grade 3 genitourinary toxicity occurred in 0.3% of patients.Conclusion
Combination androgen-deprivation therapy and 76-Gy intensity-modulated radiation therapy with gold marker implantation offers good therapeutic outcomes with few serious complications in patients with intermediate- and high-risk prostate cancer.
International Journal of Urology 02/2015; 22(5). DOI:10.1111/iju.12707 · 1.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: In PREVAIL, an international phase 3 randomized trial, treatment with ENZA decreased the risk of radiographic progression or death by 81% and the risk of death by 29% compared with placebo. We evaluated efficacy, safety and pharmacokinetic exposure with ENZA in the Japanese subgroup of patients participating in PREVAIL. Methods: Asymptomatic or mildly symptomatic chemotherapy-naïve patients with mCRPC progressing on androgen deprivation therapies were randomized 1:1 to ENZA 160 mg or placebo until discontinuation upon radiographic progression or initiation of chemotherapy. Continued androgen-deprivation therapy was required. Coprimary endpoints were overall survival (OS) and radiographic progression-free survival (rPFS). Prostate-specific antigen (PSA) response was defined as a confirmed ≥50% reduction from baseline to nadir. Results: A total of 1,717 patients (ENZA: 872, placebo: 845) were randomized in PREVAIL, of which 61 patients were Japanese (ENZA: 28, placebo: 33). The trial was halted after a planned interim analysis at which hazard ratios calculated for OS (0.71; 95%CI: 0.60-0.84) and rPFS (0.19; 95%CI: 0.15-0.23) showed significant benefit of ENZA vs placebo. Hazard ratios for OS and rPFS in Japanese patients were 0.60 (95%CI: 0.20-1.78) and 0.29 (95%CI: 0.030-2.95), respectively. Time to chemotherapy was delayed from a median 10 months on placebo vs not yet reached on ENZA, with a hazard ratio of 0.46 (95%CI: 0.22-0.96). PSA responses were more common in Japanese patients receiving ENZA (61%) vs placebo (21%) (treatment effect = 39.5%; 95%CI: 16.7%-62.3%). Plasma concentration of ENZA was slightly higher in the Japanese subgroup: geometric mean Cmin= 13.8 µg/mL vs 12.3 µg/mL in the non-Japanese cohort at 13 weeks. In the Japanese subgroup adverse events (AEs) ≥ Grade 3 were reported by 9/28 patients (32%) on ENZA vs 13/33 patients (39%) on placebo. Treatment-related AEs ≥ Grade 3 were rare: in the ENZA arm (1/28; 3.6%) and in the placebo arm (2/33; 6.1%). Conclusions: Theefficacy and safety results in the Japanese subgroup were generally consistent with the overall results from the PREVAIL trial. Clinical trial information: NCT01212991
[Show abstract][Hide abstract] ABSTRACT: Purpose:
Renal cell carcinoma (RCC) is known to express CXCR3. The function of CXCR3 on RCC has not been clarified. The aims of this study were to reveal the function of CXCR3 on RCC and to investigate the regulating factors of CXCR3.
Material and Methods:
Fifty-six clinical samples of clear cell RCC and corresponding normal renal tissue samples were obtained from surgical specimens of Japanese patients who underwent radical nephrectomy at Chiba University Hospital between 2000 and 2011. As RCC cell lines, 786-O, ACHN, and Caki-1 were used. The expression profile of CXCR3 and its splice variants were examined. For functional analyses, 786-O and interferon (IFN)-γ -inducible 10-kDa protein or IP-10 (CXCL10) were selected as the representatives.
CXCR3 and its ligands were abundant in RCC samples compared with corresponding normal kidney samples. The CXCR3-A/CXCR3-B ratio was 1.5 times higher in RCC samples than in normal kidney samples. CXCL10 treatment induced 786-O cell migration and invasion; these effects were inhibited by neutralizing antibody. The expressions of phosphorylated RhoA and pro/active matrix metalloproteinase-9 (MMP-9) were up-regulated by CXCL10 treatment. In clinical samples, the expressions of CXCR3 and CXCR3-A were significantly higher in metastatic RCC than in non-metastatic RCC. Finally, the expression of CXCR3-A and hypoxia-inducible factor 1 alpha (HIF-1-alpha) were significantly correlated in the clinical samples. Regarding 786-O, treatment with cobalt chloride (CoCl2) up-regulated CXCR3 and HIF-1-alpha expression 4.5-fold and 2.2-fold, respectively.
We showed the association of CXCR3 and RCC metastasis. The expression of CXCR3 may be regulated by hypoxia.
The Journal of urology 08/2014; 192(2). DOI:10.1016/j.juro.2014.01.100 · 3.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We report the adverse events and efficacy of traditional (4 weeks on 2 weeks off) and alternative sunitinib treatment schedules for Japanese patients with metastatic renal cell carcinoma. We retrospectively investigated 54 patients who received sunitinib for metastatic renal cell carcinoma between May 2006 and June 2012: 32 received a traditional treatment schedule and 22 received an alternative schedule. According to the Memorial Sloan-Kettering Cancer Center risk classification, five patients had favorable prognoses, 42 had intermediate prognoses and seven had poor prognoses. The mean observation periods were 16.3 and 20 months for the traditional and alternative schedule groups, respectively. Adverse events were significantly less common in the alternative schedule group, including most high-grade events. In the traditional and alternative schedule groups, median times to failure were 4.1 and 11.6 months (P = 0.040), median progression-free survival times were 4.1 and 11.3 months (P = 0.031), and median overall survival times were 12.0 and 32.1 months (P = 0.018), respectively. Each of these measures was better in the group of patients who received an alternative treatment schedule, suggesting that individualized changes to the sunitinib administration schedule can be effective.
International Journal of Urology 06/2014; 21(10). DOI:10.1111/iju.12504 · 1.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although transperineal (TP) prostate biopsy is growing in popularity, its safety has not been evaluated based on extensive studies. We prospectively assessed the adverse events associated with transrectal ultrasound (TRUS)-guided TP 16-core prostate biopsy at a single institution.
We enrolled 2,086 males who underwent first-time TRUS-guided TP prostate biopsy under lumbar spinal anesthesia at Chiba Cancer Center between 2009 and 2013. Eight adverse events were assessed prospectively using a purpose-designed questionnaire. The prevalence and duration of all adverse events were evaluated. We performed subgroup analyses for hematuria and urinary retention in relation to clinical factors.
Questionnaires were collected from 1,663 cases (79.7 %). The cancer detection rate was 53.5 % in all patients. The prevalence and duration of complications were as follows: hematuria, 73.4 % and 4.51 ± 2.88 days; perineal bleeding, 7.1 % and 2.20 ± 2.24 days; hematospermia 14.4 %; dysuria, 15.7 % and 3.12 ± 2.71 days; urinary tract pain, 49.5 % and 2.43 ± 2.08 days; perineal pain, 35.5 % and 3.53 ± 2.59 days; fever ≥37 °C, 1.7 % and 1.79 ± 1.72 days; and headache, 22.1 % and 3.40 ± 2.10 days. Seventeen patients (1.1 %) required indwelling urethral catheterization for grade 2 urinary retention. Pre-biopsy International Prostate Symptom Score (p = 0.014) was an independent related factor for hematuria. Prostate volume (p = 0.001) was an independent related factor for grade 2 urinary retention.
TRUS-guided TP prostate biopsy under lumbar spinal anesthesia can be performed safely with only minor adverse events.
The Journal of Urology 04/2014; 191(4):e595. DOI:10.1016/j.juro.2014.02.1647 · 3.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: In clinical trials with no upper age limit, the proportion of older patients is usually small, probably reflecting the more conservative approach adopted by clinicians when treating the elderly. An exploratory analysis of elderly patients in the RECORD-1 Trial showed that patients ≥ 65 y.o. had superior median PFS than overall RECORD-1 population (5.4 months and 4.9 months, respectively). We investigated the efficacy, relative benefit and safety of Everolimus (EVE) as sequential therapy after failure of VEGFr-TKI therapy for older patients with metastatic renal cell cancer (mRCC), in daily practice. Materials and Methods: 172 consecutive IRB approved patients with mRCC (median age 65, M:F 135/37, 78% clear cell) who received salvage EVE at 39 tertiary institutions between October 2009 and August 2011 were included in this analysis. Some 31% had progressed on sunitinib, 22% on sorafenib, 1% on axitinib, 41% on sequential therapy, and 5% had received other therapy. Patients with brain metastases were not included and 95% of the patients had a ECOG (Eastern Cooperative Oncology Group) performance status (PS) of 0 or 1. Previous radiotherapy was an exclusion criterion, but prior chemotherapy was permitted. Adequate organ function and hematologic parameters were mandatory. EVE administration was approved by the institutional review board at each participating institution and signed informed consent was obtained from all patients. Results: Median time of the whole cohort to last follow-up was 3.5 months (range 0.4-15.2 months). Forty four percent were continuing to take EVE at last follow- up. There were 86 (50%) patients ≥ 65 y.o. and 86 (50%) <65 y.o. The percentage of patients who showed PR/ SD was higher in the older group than in the younger one (5.9%/61.2% vs 1.2%/46.5%, respectively). Median survival of older patients was also significantly longer (3.5 +/- 0.31 vs 3.1 +/- 0.34, hazard ratio=0.45, CI; 0.255- 0.802). Analysis using Cox regression model adjusted for gender, PS, number of metastases, site of metastases, histology, smoking history and age detected an association between age and PFS (p=0.011). The frequency of adverse events in elderly patients treated with EVE was no greater than that in younger patients, although such toxicity may have had a greater impact on their quality of life. Conclusions: Older patients should not generally be excluded from accepted therapies (mTOR inhibitors after failure of VEGFr-TKI therapy) for mRCC.
Asian Pacific journal of cancer prevention: APJCP 02/2014; 15(4):1811-1815. DOI:10.7314/APJCP.2014.15.4.1811 · 2.51 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Population pharmacokinetic data suggest axitinib plasma exposure correlates with efficacy in metastatic renal-cell carcinoma. Axitinib dose titration might optimise exposure and improve outcomes. We prospectively assessed the efficacy and safety of axitinib dose titration in previously untreated patients with metastatic renal-cell carcinoma.
In this randomised, double-blind, multicentre, phase 2 study, patients were enrolled from 49 hospitals and outpatient clinics in the Czech Republic, Germany, Japan, Russia, Spain, and USA. Patients with treatment-naive metastatic renal-cell carcinoma received axitinib 5 mg twice daily during a 4 week lead-in period. Those patients with blood pressure 150/90 mm Hg or lower, no grade 3 or 4 treatment-related toxic effects, no dose reductions, and no more than two antihypertensive drugs for 2 consecutive weeks were stratified by Eastern Cooperative Oncology Group performance status (0 vs 1), and then randomly assigned (1:1) to either masked titration with axitinib to total twice daily doses of 7 mg, and then 10 mg, if tolerated, or placebo titration. Patients who did not meet these criteria continued without titration. The primary objective was comparison of the proportion of patients achieving an objective response between randomised groups. Safety analyses were based on all patients who received at least one dose of axitinib. This ongoing trial is registered with ClinicalTrials.gov, number NCT00835978.
Between Sept 2, 2009, and Feb 28, 2011, we enrolled 213 patients, of whom 112 were randomly assigned to either the axitinib titration group (56 patients) or the placebo titration group (56 patients). 91 were not eligible for titration, and ten withdrew during the lead-in period. 30 patients (54%, 95% CI 40-67) in the axitinib titration group had an objective response, as did 19 patients (34%, 22-48]) in the placebo titration group (one-sided p=0·019). 54 (59%, 95% CI 49-70) of non-randomised patients achieved an objective response. Common grade 3 or worse, all-causality adverse events in treated patients were hypertension (ten [18%] of 56 in the axitinib titration group vs five [9%] of 56 in the placebo titration group vs 45 [49%] of 91 in the non-randomised group), diarrhoea (seven [13%] vs two [4%] vs eight [9%]), and decreased weight (four [7%] vs three [5%] vs six [7%]). One or more all-causality serious adverse events were reported in 15 (27%) patients in the axitinib titration group, 13 (23%) patients in the placebo titration group, and 35 (38%) non-randomised patients. The most common serious adverse events in all 213 patients were disease progression and dehydration (eight each [4%]), and diarrhoea, vomiting, pneumonia, and decreased appetite (four each [2%]).
The greater proportion of patients in the axitinib titration group achieving an objective response supports the concept of individual axitinib dose titration in selected patients with metastatic renal-cell carcinoma. Axitinib shows clinical activity with a manageable safety profile in treatment-naive patients with this disease.
The Lancet Oncology 10/2013; 14(12). DOI:10.1016/S1470-2045(13)70464-9 · 24.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of the study was to assess the safety and efficacy of everolimus therapy for advanced renal cell carcinoma in Japanese patients receiving real-world care.
Patients who had been treated with everolimus for advanced renal cell carcinoma at 39 Japanese medical centers between January 2010 and November 2011 were retrospectively investigated to assess adverse events and the time to treatment failure.
A total of 180 patients were identified. Their median age was 65 years (range 23-93). The median time to treatment failure was 2.9 months (95% confidence interval 2.4-3.4). The median time to treatment failure was significantly longer in patients with dose modification (4.2 months; 95% confidence interval 3.4-5.0) than in patients without dose modification (1.7 months; 95% confidence interval 1.0-2.3; P < 0.01) after experiencing adverse events. Stomatitis (44%) was the most frequent adverse event, followed by thrombocytopenia (31%), anemia (22%), interstitial pneumonia (22%) and hyperglycemia (17%). Interstitial pneumonia was the most frequent cause of discontinuation in patients who discontinued everolimus due to intolerability regardless of the dose modification status. None of the patients with dose modification of everolimus discontinued everolimus due to thrombocytopenia or leukopenia.
The adverse event profile of everolimus may differ between Japanese and Caucasian patients. Dose modification of everolimus might be associated with longer treatment duration in patients with advanced renal cell carcinoma. Further studies are required to clarify this association. Interstitial pneumonia may be difficult to overcome by dose modification.
Japanese Journal of Clinical Oncology 09/2013; 43(11). DOI:10.1093/jjco/hyt121 · 1.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The incidence of prostate cancer in the Japanese population has increased because of the increase in life expectancy, consumption of westernized diets, and improvements in prostate cancer screening by using the prostate-specific antigen (PSA)test. Further, in the past 10 years, there have been great advancements in the treatment options available for prostate cancer. Radical treatment methods, such as robot-assisted surgery, intensity-modulated radiation therapy, and particle beam radiation therapy, may have anticancer effects and may improve the quality of life by preserving micturition ability and sexual function. Radiotherapy and endocrine therapy have been shown to prevent postoperative recurrence. Endocrine therapy has been demonstrated to be effective in preventing recurrence after radiotherapy. Moreover, endocrine therapy can be administered to patients at all stages of prostate cancer and is often used as the initial treatment for advanced prostate cancer, particularly in patients with metastasis. However, recurrence(relapse)after endocrine therapy is associated with a poor prognosis. In this study, we describe all the available treatment options for prostate cancer and the treatable and untreatable forms of recurrent prostate cancer.
Gan to kagaku ryoho. Cancer & chemotherapy 08/2013; 40(8):998-1002.
[Show abstract][Hide abstract] ABSTRACT: We examined the effect of neoadjuvant hormonal therapy (NHT) on biochemical failure. We retrospectively analyzed 146 high-risk prostate cancer patients (clinically (c), T1c-3N0M0) who underwent radical prostatectomy between June 2002 and March 2008. Thirty-eight patients were treated with NHT for ≥2 months (NHT group), and 108, with surgery alone (SA group). The study population comprised 89 cT1c-2N0M0 patients and 57 cT3N0M0 patients, and pathologically (p), 66 pT0-2N0M0 patients and 76 pT3N0M0 patients. Downstaging was noted in 36.4 and 0% of cT1c-2N0M0 patients and in 74.1 and 20.0% of cT3N0M0 patients in the NHT and SA groups, respectively. For both cT1c-2N0M0 and cT3N0M0 patients, the downstaging rate was significantly higher in the NHT group than in the SA group (p＜0.01). Positive resection margin rates were significantly lower in the NHT group (34.2%) than in the SA group (65.7%) (p＜0.01). The overall prostate-specific antigen (PSA) progression-free rate did not differ significantly between the 2 groups in both pT0-2N0M0 and pT3N0M0 patients. However, in pT0-2N0M0 patients with negative resection margins, the 5-year PSA progression-free rate was significantly lower in the NHT group than in the SA group (p＜0.01), whereas this rate did not differ significantly between the groups in both pT0-2N0M0 and pT3N0M0 patients with positive resection margins. Although NHT seemed to have some effect on downstaging, its pathological effects could be underestimated. Thus, NHT was considered to have no significant effect on biochemical failure.
[Show abstract][Hide abstract] ABSTRACT: Objective
Axitinib is a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors 1, 2 and 3. The efficacy and safety of axitinib in Japanese patients with metastatic renal cell carcinoma were evaluated.
A subgroup analysis was conducted in Japanese patients enrolled in the randomized Phase III trial of axitinib versus sorafenib after failure of one prior systemic therapy for metastatic renal cell carcinoma.
Twenty-five (of 361) and 29 (of 362) patients randomized to the axitinib and sorafenib arms, respectively, were Japanese and included in this analysis. Median progression-free survival in Japanese patients was 12.1 months (95% confidence interval 8.6 to not estimable) for axitinib and 4.9 months (95% confidence interval 2.8–6.6) for sorafenib (hazard ratio 0.390; 95% confidence interval 0.130–1.173; stratified one-sided P = 0.0401). The objective response rate was 52.0% for axitinib and 3.4% for sorafenib (P = 0.0001). The common all-causality adverse events (all grades) in Japanese patients were dysphonia (68%), hypertension (64%), hand–foot syndrome (64%) and diarrhea (56%) for axitinib, and hand–foot syndrome (86%), hypertension (62%) and diarrhea (52%) for sorafenib. The safety profiles of axitinib and sorafenib in Japanese patients were generally similar to those observed in the overall population, with the exceptions of higher incidences of hypertension, dysphonia, hand–foot syndrome, hypothyroidism and stomatitis.
Axitinib is efficacious and well tolerated in Japanese patients with previously treated metastatic renal cell carcinoma, consistent with the results in the overall population, providing a new targeted therapy for these Japanese patients.
Japanese Journal of Clinical Oncology 04/2013; 43(6). DOI:10.1093/jjco/hyt054 · 1.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background. The aim of this study was to determine concordance rates for prostatectomy specimens and transrectal needle biopsy samples in various areas of the prostate in order to assess diagnostic accuracy of the transrectal biopsy approach, especially for presurgical detection of cancer in the prostatic apex.
Materials and Methods. From 2006 to 2011, 158 patients whose radical prostatectomy specimens had been evaluated were retrospectively enrolled in this study. Concordance rates for histopathology results of prostatectomy specimens and needle biopsy samples were evaluated in 8 prostatic sections (apex, middle, base, and transitional zones bilaterally) from 73 patients diagnosed at this institution, besides factors for detecting apex cancer in total 118 true positive and false negative apex cancers.
Results. Prostate cancer was found most frequently (85%) in the apex of all patients. Of 584 histopathology sections, 153 (49%) from all areas were false negatives, as were 45% of apex biopsy samples. No readily available preoperative factors for detecting apex cancer were identified. Conclusions. In Japanese patients, the most frequent location of prostate cancer is in the apex. There is a high false negative rate for transrectal biopsy samples. To improve the detection rate, transperitoneal biopsy or more accurate imaging technology is needed.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: The aim of this study was to retrospectively investigate clinical outcomes by relative dose and dose intensity of docetaxel (DOC) as chemotherapy for Japanese patients with castration-resistant prostate cancer (CRPC). METHODS: A total of 145 CRPC patients who received more than 4 courses of DOC chemotherapy at 14 hospitals between 2005 and 2011 were enrolled. Patients were divided into two groups-those receiving a higher or lower dose (mg/m(2)) or dose intensity (mg/m(2)/week). Differences between the groups regarding treatment outcomes and adverse events (AEs) were determined. Additionally, prognostic factors predictive of cancer-specific survival (CSS) in these patients were identified by both univariate and multivariate analysis. RESULTS: The total patient group underwent a mean of 11.2 ± 7.4 DOC cycles, and the mean CSS after therapy was 15.6 ± 10.1 months. The higher-dose group had a better prostate-specific antigen (PSA) response than the lower-dose group. However, there was no significant difference between the groups in prognosis after DOC chemotherapy. Leukopenia and neutropenia were observed more frequently in the higher-dose group. Serum biomarkers (including PSA, lactate dehydrogenase and alkaline phosphatase), hemoglobin levels and presence of pain at initiation of chemotherapy, as well as the PSA nadir level on first-line hormone therapy, all were significant predictors of CSS. CONCLUSIONS: In the Japanese population, relatively low-dose DOC chemotherapy had no deleterious effect on the CSS of CRPC patients, and a lower incidence of AEs occurred, in spite of a diminished PSA response compared with those receiving a higher dose.
International Journal of Clinical Oncology 01/2013; 189(4). DOI:10.1007/s10147-012-0510-9 · 2.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: PURPOSE: In analysis of a bladder diary with the patient's self-reported urinary perception grades, we developed a quantitative measure of bladder hypersensitivity, which we refer to as the urge perception index (UPI). The aim of this study was to evaluate the impact of the UPI on defining the severity of overactive bladder (OAB). MATERIALS AND METHODS: We retrospectively evaluated 69 female patients to visit our outpatient clinic with complaining storage symptoms. The patients were asked to complete OAB symptom score, and a 3-day bladder diary with a self-reported grading of urinary perception (range 1 to 5) per void, and diagnosed as OAB (n=43) or non-OAB (n=26). UPI was defined as a quotient of voided volume/urinary perception grade at every single void. RESULTS: A total of 1578 voids reporting were analysed. According to the grade of urinary perception, values of UPI in OAB demonstrated significantly lower values than those in non-OAB (p<0.001 in all perception grades of 1-4). The averages of UPIs in 3-day bladder diary was lower in OAB (55±28) than non-OAB (133±73) (p<0.0001). The most severe (the lowest) single UPI value during the 3-day was significantly lower in OAB (20±12) than non-OAB (62±40) (p<0.0001). There were negative linear correlations of UPI value with total OAB symptom scores (r=-0.598, p<0.0001) and with a symptom score of urgency (r=-0.557, p<0.0001). CONCLUSIONS: UPI, the integrated parameter of patient-reported bladder perception and voided volume, could be promising for quantifying the severity of OAB or bladder hypersensitivity through the analysis of a bladder diary.
The Journal of urology 11/2012; DOI:10.1016/j.juro.2012.11.117 · 3.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Temsirolimus, an inhibitor of the mammalian target of rapamycin, is approved for treatment of patients with advanced renal cell carcinoma in the USA and Europe. Temsirolimus was not yet evaluated in East Asian patients.
This non-randomized Phase II study enrolled 82 patients with advanced renal cell carcinoma [20 (24%) Japanese, 30 (37%) Korean and 32 (39%) Chinese patients; median age (range): 55 (26-83) years]. Most (71%) received prior systemic therapy for metastatic disease; two-thirds were intermediate risk. Six Japanese patients received intravenous temsirolimus 20 mg/m(2) weekly for tolerability assessment (Group A); the remaining 76 received a 25 mg flat dose weekly (Group B). Temsirolimus was dosed once weekly. Primary efficacy end point was the Response Evaluation Criteria in Solid Tumors-defined clinical benefit rate in the intent-to-treat population.
In the entire population, regardless of treatment group, the clinical benefit rate was 48% (95% confidence interval: 36, 59). Objective response rate was 11% (95% confidence interval: 5, 20), median progression-free survival was 7.3 months (95% confidence interval: 4.0, 9.2) and median time to treatment failure was 5.4 months (95% confidence interval: 3.5, 7.4). No patient in Group A demonstrated dose-limiting toxicity. The most frequent Grade 3 or 4 drug-related adverse events were anemia, hyperglycemia, hypophosphatemia and stomatitis (5% each). Serious adverse events reported in ≥ 5% of patients were pneumonia (9%) and interstitial lung disease (7%). Temsirolimus and its major metabolite, sirolimus, were long-lived throughout the dosage interval, with no evidence of accumulation.
Temsirolimus was well tolerated and showed promising activity in Japanese, Korean and Chinese patients with advanced renal cell carcinoma.
Japanese Journal of Clinical Oncology 07/2012; 42(9):836-44. DOI:10.1093/jjco/hys110 · 1.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Fork-head box protein A1 (FOXA1) is a "pioneer factor" that is known to bind to the androgen receptor (AR) and regulate the transcription of AR-specific genes. However, the precise role of FOXA1 in prostate cancer (PC) remains unknown. In this study, we report that FOXA1 plays a critical role in PC cell proliferation. The expression of FOXA1 was higher in PC than in normal prostate tissues (P = 0.0002), and, using immunohistochemical analysis, we found that FOXA1 was localized in the nucleus. FOXA1 expression levels were significantly correlated with both PSA and Gleason scores (P = 0.016 and P = 0.031, respectively). Moreover, FOXA1 up-regulation was a significant factor in PSA failure (P = 0.011). Depletion of FOXA1 in a prostate cancer cell line (LNCaP) using small interfering RNA (siRNA) significantly inhibited AR activity, led to cell-growth suppression, and induced G0/G1 arrest. The anti-proliferative effect of FOXA1 siRNA was mediated through insulin-like growth factor binding protein 3 (IGFBP-3). An increase in IGFBP-3, mediated by depletion of FOXA1, inhibited phosphorylation of MAPK and Akt, and increased expression of the cell cycle regulators p21 and p27. We also found that the anti-proliferative effect of FOXA1 depletion was significantly reversed by simultaneous siRNA depletion of IGFBP-3. These findings provide direct physiological and molecular evidence for a role of FOXA1 in controlling cell proliferation through the regulation of IGFBP-3 expression in PC.
PLoS ONE 04/2012; 7(8):e42456. DOI:10.1371/journal.pone.0042456 · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess the efficacy and safety of degarelix, a new gonadotropin-releasing hormone antagonist, for achieving and maintaining serum testosterone suppression (≤0.5 ng/ml) during the 12-month treatment of Japanese patients with prostate cancer.
This Phase II study was conducted as a multicentre, randomized, parallel-group, open-label study. A total of 273 patients with adenocarcinoma of the prostate (any stage) were treated. Degarelix was administered subcutaneously at an initial dose of 240 mg followed by monthly maintenance doses of either 80 or 160 mg for a total of 12 doses. The treatment continued for 12 months.
Dose regimens of 240/80 and 240/160 mg maintained castrate levels of testosterone in 94.5 and 95.2% of the patients, respectively. After 3 days, 99.3 and 98.5% of the patients, respectively, reached these levels without a testosterone surge. Prostate-specific antigen levels decreased rapidly following degarelix administration and remained low throughout the study. Best overall response rates according to RECIST were 71.4 (20/28) and 72.7% (16/22), respectively. Eighteen patients (6.6%) withdrew from the study due to adverse events. The most common adverse events were injection site reactions; other adverse events included hot flush, nasopharyngitis, weight increase and pyrexia.
Both monthly degarelix dosing regimens were found to be effective in testosterone suppression without a testosterone surge, prostate-specific antigen reductions and anti-tumour effect in Japanese patients with prostate cancer, as was shown in the overseas Phase III study. Degarelix was also well tolerated.
Japanese Journal of Clinical Oncology 03/2012; 42(6):477-84. DOI:10.1093/jjco/hys035 · 1.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to establish the discriminating accuracy of Kanao's pre-operative nomogram for renal cell carcinoma in predicting cause-specific survival among representative patients who underwent nephrectomy. Patients originated from two centers: Chiba University Hospital (n= 151) and Chiba Cancer Center (n = 91). We validated the predictive accuracy, which was assessed using Harrell's concordance-index. The concordance-index values were 0.692 and 0.834 for Chiba University Hospital and Chiba Cancer Center, respectively, although it was 0.822 for the combined data sets. Results of external validation were different at each cohort. We constructed calibration plots of Kanao's nomogram and confirmed the tendency at each institution. Inconsistency of results among two centers makes it difficult to reach a valid conclusion. Therefore, the predictive accuracy of Kanao's nomogram was not settled. Clinicians need to confirm the predictive accuracy of Kanao's nomogram and construct calibration plots when applying this nomogram to different patient populations.
Japanese Journal of Clinical Oncology 08/2011; 41(9):1147-51. DOI:10.1093/jjco/hyr101 · 1.75 Impact Factor