Masayuki Maruoka

Combination of Gemcitabine and Paclitaxel as Second-line Chemotherapy for Advanced Urothelial Carcinoma

OBJECTIVE The aim of this study was to evaluate the efficacy and toxicities of the gemcitabine and paclitaxel combination regimen as second-line chemotherapy for patients with advanced or metastatic urothelial carcinoma (UC) who have previously been treated with platinum-based chemotherapy for the metastatic disease. METHODS Thirty-three patients with advanced or metastatic UC who had received platinum-based chemotherapy were treated with an outpatient gemcitabine and paclitaxel combination regimen. A dose of 180 mg/m(2) paclitaxel was administered by intravenous (IV) infusion on Day 1, and 1000 mg/m(2) gemcitabine was administered by IV on Days 1, 8 and 15.The course was repeated every 28 days. Patients were evaluated after every 2 cycles of therapy using computed tomography. RESULTS Of the 33 patients enrolled in this study, 30 could be evaluated to determine treatment efficacy; 10 had an objective response [overall response rate: 33.3%, 95% confidence interval (CI), 19.2-51.2%]. The median overall survival was 11.3 months (95% CI, 7.2-13.6 months). The chemotherapy sensitivity differed with disease site. The response rates of lung and bone metastases were 27% and 14%, and the progressive disease (PD) rates of lung and bone metastases were 13% and 14%, respectively. On the other hand, the response rate of liver metastasis was 14%, and its PD rate was 57%. None of the patients (n = 3) with adrenal metastasis responded to this regimen. Toxicities were mild, and no life-threatening complications occurred. CONCLUSIONS Gemcitabine and paclitaxel combination therapy is a tolerable and active regimen for patients with advanced UC after failure of platinum-based chemotherapy.

THE IMPACT OF A 4 CM. CUTOFF POINT FOR STRATIFICATION OF T1N0M0 RENAL CELL CARCINOMA AFTER RADICAL NEPHRECTOMY

PURPOSE The 1997 TNM classification defines T1 tumors as those smaller than 7 cm. Recently, a cutoff point of 4 cm. has been proposed to create a subclass of T1 tumors. We evaluated the validity of this cutoff point by assessing the pathological findings and prognoses of patients with T1N0M0 renal cell carcinoma following radical nephrectomy. MATERIALS AND METHODS We reviewed the hospital charts of 333 patients with T1N0M0 tumors, followed as long as 282 months (median 63) after radical nephrectomy. The validity of tumor size cutoff point for predicting survival outcome was tested in relation to other prognostic factors, including patient age, tumor position, nuclear grade, tumor histopathology and degree of microscopic venous invasion. RESULTS During followup 32 patients (9.6%) had tumor recurrence and 21 (6.3%) died of renal cell carcinoma. A 5 cm. cutoff point maximized the differences in cancer specific survival rates and a 4 cm. cutoff point maximized the differences in disease-free survival rates. Tumor size was directly related to microscopic venous invasion and nuclear grade, which are significant prognostic factors, and a 4 cm. cutoff point enhanced these relationships. CONCLUSIONS Tumor size is an important prognostic factor for patients with T1N0M0 renal cell carcinoma. A cutoff point of 4 cm. is practical for dividing the T1N0M0 classification into T1a and T1b subclasses.

Phase III Trial of Everolimus in Metastatic Renal Cell Carcinoma: Subgroup Analysis of Japanese Patients from RECORD-1

Objective To assess the efficacy and safety of everolimus in Japanese patients with metastatic renal cell carcinoma. Methods A subgroup analysis of the pivotal Phase III, randomized, double-blind, placebo-controlled trial of everolimus 10 mg/day in patients with disease progression after treatment with sorafenib, sunitinib or both assessed outcomes in Japanese participants. Results were compared with those for the overall study population. Results The final trial analysis included 24 Japanese patients (everolimus, n= 15; placebo, n = 9). Median progression-free survival in the Japanese subpopulation was 5.75 months (95% confidence interval, 4.90 months to not reached) with everolimus and 3.61 months (95% confidence interval, 1.91–9.03 months) with placebo (hazard ratio, 0.19; 95% confidence interval, 0.05–0.83). Median overall survival was not reached with everolimus and was 14.9 months (95% confidence interval, 11.0–16.8 months) with placebo (hazard ratio, 0.30; 95% confidence interval, 0.07–1.27). Overall, efficacy and safety were similar when comparing the Japanese and overall populations. In the Japanese subpopulation, the most common adverse events with everolimus were stomatitis, infections and rash. Four Japanese subjects (27%) developed Grade 1 (n = 2) or 2 (n = 2) pneumonitis (all reversible and allowing for continuation of therapy, after interruption, steroids and dose reduction for both Grade 2 cases), with a lower pneumonitis incidence of 14% in the overall population (albeit associated with a Grade 3 incidence of 4%). Conclusions These findings suggest that the demonstrated benefits of everolimus in the overall trial population are similar in Japanese patients with metastatic renal cell carcinoma.

Renal cell carcinoma with unusual metastasis to the gallbladder

Gallbladder involvement in patients with renal cell carcinoma (RCC) is extremely rare. We present a report of a 61-year-old man with a synchronous RCC metastasis to the gallbladder presenting as an intraluminal polypoid mass simulating primary gallbladder carcinoma. Enhanced abdominal computed tomography demonstrated a well-enhanced polypoid lesion in the gallbladder. Intraoperative rapid pathological examination of the gallbladder tumor showed clear cell-type cancerous cells. Microscopically, tumor cells of both the resected kidney and gallbladder had round uniform nuclei, clear cytoplasm, and well-defined cytoplasmic borders, forming alveolar patterns. Immunohistochemically, the tumor cells were negative for cytokeratin 7 (CK7) and carcinoembryonic antigen (CEA), which is usually positive in primary clear cell carcinoma of the gallbladder. Therefore, the final diagnosis was RCC with a synchronous gallbladder metastasis.

Transperineal ultrasound-guided 12-core systematic biopsy of the prostate for patients with a prostate-specific antigen level of 2.5–20 ng/ml in Japan

BackgroundThe aim of this study was to investigate the cancer detection rate in patients with a prostate-specific antigen (PSA) level of 2.5 to 20 ng/ml, using transperineal ultrasound-guided systematic biopsy of the prostate.MethodsThree hundred consecutive patients with PSA levels of 2.5 to 20 ng/ml underwent transperineal ultrasound-guided 12-core systematic biopsy of the prostate.ResultsProstate cancer was detected in 108 of the 300 patients (36.0%). The cancer detection rates in patients with total PSA levels of 2.5–4.0, 4.01–10.0 and 10.01–20.0 ng/ml were 18.2%, 31.0%, and 50.0%, respectively. The cancer detection rates in patients with prostate volumes of less than 30 cc and over 50 cc were almost 50%, and 13.3%, respectively. The cancer detection rate in patients with a PSA density (PSAD) of less than 0.10 ng/ml per cc was only 5.6%, and no prostate cancer was detected in patients with a free-to-total PSA ratio (% f PSA) over 40%.ConclusionWe demonstrated a high prostate cancer detection rate by the transperineal ultrasound-guided 12-core systematic biopsy method in patients with PSA levels of 2.5 to 20 ng/ml. Accordingly, if the number of core biopsies is further increased overall, except in patients with a large prostate volume, and if the indication for biopsy is decided based on the PSAD and %f PSA, then the cancer detection rate by the present method may be further improved, with fewer unnecessary biopsies.

External validation and head‐to‐head comparison of Japanese and Western prostate biopsy nomograms using Japanese data sets

The objective of this study was to perform external validation of a previously developed prostate biopsy nomogram (the CHIBA nomogram) and to compare it with previously published nomograms developed in Japanese and overseas populations. Two different cohorts of patients were used: one from the Chiba Cancer Center (n = 392) in which transperineal 16‐core biopsy was performed, and another from Chibaken Saiseikai Narashino Hospital (n = 269) in which transrectal 16‐core biopsy was carried out. All patients were Japanese men with serum prostate‐specific antigen levels less than 10 ng/mL. The predictive accuracy of our CHIBA nomogram and of four other published nomograms (Finnes sextant biopsy‐based logistic regression model, Karakiewiczs sextant biopsy‐based nomogram, Chuns 10‐core biopsy‐based nomogram and Kawakamis three‐dimensional biopsy‐based nomogram) was quantified based on area under the curve derived from receiver operating characteristic curves. Head‐to‐head comparison of area under the curve values demonstrated that our nomogram was significantly more accurate than all other models except Chuns (P = 0.012 vs Finnes, P = 0.000 vs Karakiewiczs, and P = 0.003 vs Kawakamis). Our nomogram appears to be more useful for the Japanese population than Western models. Moreover, external validation demonstrates that its predictive accuracy does not vary according to biopsy approach. This is the first report to demonstrate that the predictive accuracy of a nomogram is independent from the biopsy method.

Treatment outcomes of sorafenib for first line or cytokinerefractory advanced renal cell carcinoma in Japanese patients

The objective of the present study was to document the treatment efficacy and safety of sorafenib in Japanese patients with advanced renal cell carcinoma (RCC). A retrospective analysis of 50 consecutive patients with metastatic RCC between January 2005 and December 2009 was carried out. Patients received sorafenib after failed cytokine therapy or first‐line sorafenib treatment. All received 400 mg of sorafenib orally twice daily. Five of 14 patients with bone metastases were also given bisphosphonates. Tumor response was evaluated every 1–2 months according to the Response Evaluation Criteria in Solid Tumors. Adverse events (AE) were evaluated at each visit during and after treatment, and were recorded according to the National Cancer Institutes Common Terminology Criteria for Adverse Events version 3.0. Dose modification of sorafenib was permitted if grade 3 or 4 AE occurred. Treatment continued until disease progression or treatment intolerance occurred. Partial response, and stable disease as best objective responses were observed in 11 (22%) and 23 (46%) patients, respectively. Median progression‐free survival was 7.3 months and median overall survival was 11.9 months. All patients experienced AE and one or more grade 3/4 AE occurred in 43 of 50 (86%) patients. Although it requires close monitoring, sorafenib treatment seemed to be effective in the present study population.

Binding of Dihydrotestosterone, R 1881 and R 5020 in Cytosols from Normal, Benign Hypertrophic and Cancerous Human Prostates

The binding of dihydrotestosterone, R 1881 and R 5020 was examined in cytosols of normal, benign hypertrophic and cancerous tissues of the human prostates. Almost all samples obtained by open operation showed high affinity binding to these ligands. Dissociation constants of the binding to these ligands were approximately 10(-9) M irrespective of the pathological state of the prostates. Maximum binding sites for dihydrotestosterone seemed to be greater in normal tissues than in the pathological ones. However, maximum binding sites for R 1881 and R 5020 were not significantly different among the normal and pathological prostates examined in the present study. Moreover, some correlation was observed between the maximum binding sites for R 1881 and those for R 5020. The samples resected by TUR seemed to be inadequate for analyses of androgen binding.

Multi-modal treatment of primarily using continuous subcutaneous interferon-α injection in combination with surgery and/or radiotherapy

Abstract  Purpose: Thirty‐nine renal cell carcinoma patients with bony metastasis were intensively treated, primarily with immunotherapy using natural type interferon‐α (IFN‐α) continuous subcutaneous injection in combination with surgical resection and radiation therapy. Long‐term survival was achieved, including three patients with complete response. The results of this study are presented.

CLINICAL STUDY OF BILATERAL METACHRONOUS TESTICULAR TUMORS WITH DIFFERENT HISTOLOGICAL FINDINGS

Seventy-seven patients with primary malignant testicular tumors were treated in our hospital. Twenty-five of them were given antineoplastic agents containing cis diamine dichloro platinum (CDDP). In three long-term survivors, new malignant testicular tumors developed meta-chronously and had different histological findings from those of the initial tumors. Case 1. A 28-year-old patient with a yolk sac tumor of the left testicle, stage IIO, developed metastasis to the supraclavicular lymph nodes five years after radiation. Chemotherapy containing of VP-16 (837 mg), CDDP (1050 mg), vincristine (32 mg), bleomycin (480 mg), and actinomycin-D (16 mg) achieved complete remission. Four years 11 months later a seminoma of the contralateral testicle, stage I, was disclosed and he died of cancer 11 years and four months after the onset of the initial disease. Case 2. A 30-year-old patient with testicular teratoma, stage IIIA, on the right side gained complete remission after a CDDP containing chemotherapy. One year and four months after the beginning of the CDDP use (1,300 mg totally as CDDP) a seminoma on the contralateral side, stage I, was detected. He died of cancer eight years and two months after his initial tumor was detected. Case 3. A 37-year-old patient with combined tumor of seminoma and yolk sac tumor of the right testicle, stage IIIO, was free from disease for six years and five months under chemotherapy. At this point a seminoma, stage I, of the contralateral testicle was newly found and treated by radiation.(ABSTRACT TRUNCATED AT 250 WORDS)