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1.
Br J Cancer ; 110(10): 2472-8, 2014 May 13.
Article in English | MEDLINE | ID: mdl-24736579

ABSTRACT

BACKGROUND: There has been no previous study on the activity of gemcitabine in combination with oxaliplatin (GemOx) for castration-resistant prostate cancer (CRPC). METHODS: The GemOx was preclinically tested for cytotoxic activity in human prostate cancer cell lines. Clinically, patients with CRPC who failed prior docetaxel were treated with gemcitabine 1000 mg m(-2) and oxaliplatin 100 mg m(-2) intravenously every 2 weeks and prednisolone 5 mg orally twice daily. The primary end point was the prostate-specific antigen (PSA) response rate. RESULTS: The GemOx displayed synergistic effects based on Chou and Talalay analysis. In the phase II study, 33 patients were accrued. The median dose of docetaxel exposure was 518 mg m(-2). A total of 270 cycles were administered with a median of eight cycles per patient. A PSA response rate was 55% (95% CI, 38-72) and radiologic response rate was 82% (9 out of 11). With a median follow-up duration of 20.5 months, the median time to PSA progression was 5.8 months (95% CI, 4.4-7.2) and the median overall survival was 17.6 months (95% CI, 12.6-22.6). The most frequently observed grade 3 or 4 toxicities were neutropenia (13%) and thrombocytopenia (13%). CONCLUSIONS: The GemOx is active and tolerable in patients with metastatic CRPC after docetaxel failure (NCT 01487720).


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Prostatic Neoplasms/drug therapy , Salvage Therapy , Adenocarcinoma/blood , Adenocarcinoma/radiotherapy , Adenocarcinoma/secondary , Aged , Aged, 80 and over , Antineoplastic Agents, Hormonal/pharmacology , Antineoplastic Agents, Hormonal/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cell Line, Tumor/drug effects , Combined Modality Therapy , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Deoxycytidine/analogs & derivatives , Deoxycytidine/pharmacology , Disease-Free Survival , Docetaxel , Drug Resistance, Neoplasm , Drug Synergism , Humans , Infusions, Intravenous , Inhibitory Concentration 50 , Kaplan-Meier Estimate , Male , Middle Aged , Neutropenia/chemically induced , Organoplatinum Compounds/administration & dosage , Organoplatinum Compounds/adverse effects , Organoplatinum Compounds/pharmacology , Oxaliplatin , Prednisolone/administration & dosage , Prednisolone/adverse effects , Prostate-Specific Antigen/blood , Prostatic Neoplasms/blood , Prostatic Neoplasms/pathology , Prostatic Neoplasms/radiotherapy , Taxoids/pharmacology , Taxoids/therapeutic use , Thrombocytopenia/chemically induced , Treatment Outcome , Gemcitabine
2.
J Hum Hypertens ; 27(9): 539-44, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23466877

ABSTRACT

To assess the impact of simple renal cyst (SRC) on hypertension, we evaluated the prevalence of SRC as well as the relationship between SRC and hypertension. Data were obtained from 29 666 participants who underwent general health screening tests in 2006. Only participants who underwent contrast-enhanced computed tomography or abdominal ultrasonography were included in our study population. We then correlated the clinical characteristics and parameters of hypertension with the presence or absence of renal cysts. Of all the enrolled participants, 5674 (19.2%) had radiologic evidence of SRC, and hypertension was diagnosed in 9865 participants (33.4%). The SRC had a multivariable-adjusted odds ratio (OR) of 1.28 (95% confidence interval (CI), 1.20-1.36) for the presence of hypertension. In study participants with multiple cysts (>1), a large cyst (4 cm in diameter) or a peripheral cyst location, the ORs for the presence of hypertension were 1.31 (95% CI, 1.19-1.44), 1.29 (95% CI, 1.06-1.56) and 1.33 (95% CI, 1.11-1.64), respectively, compared with those for study participants without cyst after adjusting for other variables. We found the presence of SRC to be associated with a significantly increased incidence of hypertension. In addition, the cyst number, size and location are important characteristics of SRC related to hypertension.


Subject(s)
Cysts/epidemiology , Hypertension/epidemiology , Kidney Diseases/epidemiology , Adult , Age Factors , Aged , Aged, 80 and over , Body Mass Index , Cohort Studies , Female , Humans , Incidence , Male , Middle Aged , Multivariate Analysis , Retrospective Studies , Risk Factors , Sex Factors
3.
Br J Cancer ; 98(1): 86-90, 2008 Jan 15.
Article in English | MEDLINE | ID: mdl-18087289

ABSTRACT

We investigated the safety and efficacy of a methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) combination regimen as second-line chemotherapy for patients with advanced or metastatic transitional cell carcinoma who failed first-line gemcitabine and cisplatin (GC) chemotherapy. Thirty patients who had progressed or relapsed after GC chemotherapy as first-line treatment were enrolled in this study. The major toxicities were neutropaenia and thrombocytopaenia. A grade 3 or 4 neutropaenia occurred in 19 (63.3%) and a grade 3 or 4 thrombocytopaenia developed in nine patients (30.0%). There were no life-threatening complications during the study. The overall response was 30%. A complete response was achieved in two patients (6.7%) and a partial response in seven (23.3%). The overall disease control rate was 50%. Seven out of 16 patients who had responded previously to GC responded to M-VAC, while 2 out of 14 who had not responded to GC responded to M-VAC. The median response duration was 3.9 months and the median progression-free survival was 5.3 months. The median overall survival was 10.9 months. M-VAC showed encouraging efficacy and reversible toxicities in patients who had progressed after GC chemotherapy and, especially, M-VAC appears to be a reasonable option as a sequential treatment regimen in patients who responded previously to GC chemotherapy.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Transitional Cell/drug therapy , Drug Resistance, Neoplasm , Kidney Neoplasms/drug therapy , Adult , Aged , Carcinoma, Transitional Cell/secondary , Cisplatin/administration & dosage , Cisplatin/therapeutic use , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Doxorubicin/therapeutic use , Female , Humans , Kidney Neoplasms/pathology , Male , Methotrexate/therapeutic use , Middle Aged , Salvage Therapy , Survival Rate , Treatment Failure , Treatment Outcome , Vinblastine/therapeutic use , Gemcitabine
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