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Kawashima A.,Osaka University | Tsujimura A.,Osaka University | Takayama H.,Osaka University | Arai Y.,Japan National Cardiovascular Center Research Institute | And 6 more authors.
International Journal of Urology

Objectives: Hyponatremia is reported to be associated with poor survival in localized renal cell carcinoma and metastatic renal cell carcinoma treated with immunotherapy. However, there are no reports on the relationship between hyponatremia and prognosis of metastatic renal cell carcinoma treated with molecular targeted therapy. We evaluated the prognostic significance of hyponatremia in metastatic renal cell carcinoma treated with molecular targeted therapy as first-line therapy. Methods: We retrospectively analyzed a database comprising 87 patients treated from April 2008 to July 2011 with sorafenib or sunitinib as first-line therapy for metastatic renal cell carcinoma. Patients were divided into three groups according to serum sodium level: severe hyponatremia (≤134mEq/L), mild hyponatremia (135-137mEq/L) and normal natremia (≥138mEq/L). Results: Median cancer-specific survival time was 8.8months in the patients with severe and mild hyponatremia, and 32.6months in the patients with normal natremia (P<0.001). Multivariate analysis showed severe and mild hyponatremia to be significantly associated with cancer-specific survival (hazard ratio 6.228; 95% confidence interval 2.161-17.947, P=0.001; hazard ratio 3.374; 95% confidence interval 1.294-8.798, P=0.013), respectively. Neutrophilia and high C-reactive protein level (C-reactive protein ≥1.0mg/dL) were significant prognostic factors to predict inferior cancer-specific survival. In Harrell's concordance index calculation, hyponatremia could significantly improve the predictive accuracy for estimation of survival probability (P=0.028). Conclusions: Hyponatremia (<138mEq/L), neutrophilia and high C-reactive protein levels seem to represent significant predictive factors for cancer-specific survival in metastatic renal cell carcinoma patients treated with molecular targeted therapy as first line therapy. Furthermore, hyponatremia might be significantly associated with chronic inflammation and tumor aggressiveness. © 2012 The Japanese Urological Association. Source

Kawashima A.,Osaka University | Tsujimura A.,Osaka University | Takayama H.,Osaka University | Arai Y.,Japan National Cardiovascular Center Research Institute | And 8 more authors.
Medical Oncology

Sunitinib is a multikinase inhibitor used as first- and second-line treatment of metastatic renal cell carcinoma. However, there are few reports on the necessary doses of sunitinib to get better clinical outcome in general practice with Japanese patients. We examined the relationship between the efficacy and the necessary doses of sunitinib therapy in a multi-institutional retrospective study. A study population of 94 metastatic renal cell carcinoma patients was eligible for this investigation. The most frequent grade 3/4 laboratory adverse events were decreased platelet (31.9 %) and white blood cell (21.3 %) counts. Treatment was discontinued in 18 patients (31.0 %) initially receiving a 50-mg/day dose within only one course, and median 1-month relative dose intensity was 74.3 %. Median progression-free survival time was 2.3 months in patients treated for only one course and 10.8 months in patients treated for more than one course (P < 0.001). Multivariate analysis showed that only one course of treatment and 60 % and less of 1-month relative dose intensity were significantly associated with inferior progression-free survival (P < 0.001 and P = 0.027, respectively). Moreover, modified Memorial Sloan-Kettering Cancer Center poor risk was significantly associated with progression-free survival time. It is difficult for Japanese patients to continue an initial dose of sunitinib therapy without drug withdrawal. Continuing therapy for more than one course and maintaining more than 60 % of 1-month relative dose intensity were very important in the prolongation of progression-free survival time regardless of the initial treatment doses. © 2012 Springer Science+Business Media, LLC. Source

Kawashima A.,Osaka University | Nakai Y.,Osaka University | Nakayama M.,Japan National Cardiovascular Center Research Institute | Ujike T.,Osaka Rosai Hospital | And 9 more authors.
World Journal of Urology

Purpose: To determine through the analysis of our multi-institutional database whether postoperative adjuvant chemotherapy for upper urinary tract carcinoma with localized invasive upper urinary tract carcinoma (UUTC) is beneficial. Methods: A study population of 93 patients with pT3N0/xM0 UUTC was eligible for this study. Clinical features evaluated were sex, tumor location, adjuvant chemotherapy status, tumor pathology (histology, grade, infiltrating growth, lymphovascular invasion (LVI)), and cause of death. Cancer-specific survival (CSS) was estimated by Kaplan-Meier method. Prognostic factors related to CSS were analyzed by Cox proportional hazards regression model for multivariate analysis. Results: In pT3 patients, overall 5-year CSS rate was 68.4% and median CSS time was 31 months (range 3-114 months). In the adjuvant chemotherapy group, 5-year CSS rate was 80.8%, whereas 5-year CSS rate was 64.4% in the non-adjuvant chemotherapy group. By multivariate analysis, adjuvant chemotherapy status was significantly associated with CSS (P = 0.008) were sex, tumor grade, tumor histology, and LVI presence. Conclusions: This study, although it was retrospective study, revealed that adjuvant chemotherapy after RNU may be beneficial in pT3N0/X patients by multivariate analysis. Prospective studies evaluating adjuvant therapy regimens for UTTC are required. © 2011 Springer-Verlag. Source

Tanigawa G.,Osaka General Medical Center Hospital | Kawashima A.,Osaka University | Yamaguchi S.,Osaka General Medical Center Hospital | Nishimura K.,Japan National Cardiovascular Center Research Institute | And 8 more authors.
Japanese Journal of Clinical Oncology

Objective: Effects of sorafenib in general clinical practice, especially those with patients of Asian ethnicity, have been rarely investigated. We assessed efficacy, safety and prognostic factors for progression-free survival in Japanese patients receiving sorafenib for advanced renal cell carcinoma. Methods: We performed a retrospective analysis of 159 Japanese patients with renal cell carcinoma. Progression-free survival was estimated by the Kaplan-Meier method. Objective response (per Response Evaluation Criteria in Solid Tumors) and safety were assessed. Cox proportional hazards model was used to identify independent prognostic factors for progression-free survival. Results: The median progression-free survival was 9.0 months (95% confidence interval, 7.5-10.6 months). In 142 patients with measurable lesions, the objective response rate was 21.8%, and disease control was achieved in 85 (59.9%) patients. Adverse events of any grade occurred in 152 patients (95.6%). Most common adverse events causing discontinuation or interruption of sorafenib were hand-foot skin reaction (22%), rash (10.7%) and liver dysfunction (10.7%). Dose reduction or therapy interruption due to adverse events was required in 128 patients (80.5%). Univariate and multivariate analysis revealed that favorable prognosis according to Memorial Sloan-Kettering Cancer Center prognostic factors and relative dose intensity during the first month of treatment of ≥50% were significant factors for predicting superior progression-free survival with sorafenib treatment. Conclusions: Sorafenib was effective in Japanese patients with advanced renal cell carcinoma in general clinical practice and was tolerated although most patients required dose reduction or interruption of therapy. Future studies should establish new strategies for treatment without sacrificing both efficacy and patient quality of life. © The Author (2011). Published by Oxford University Press. All rights reserved. Source

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