| 1. |
- Pili, Roberto, et al.
(författare)
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Phase II Randomized, Double-Blind, Placebo-Controlled Study of Tasquinimod in Men With Minimally Symptomatic Metastatic Castrate-Resistant Prostate Cancer
- 2011
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Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 29:30, s. 4022-4028
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The activity of the novel antitumor agent tasquinimod (TASQ) with S100A9 as a molecular target was investigated in men with metastatic castration-resistant prostate cancer (CRPC) and minimal symptoms. Patients and Methods: We conducted a randomized, double-blind, placebo-controlled phase II trial in men assigned (at a ratio of two to one) to either oral once-daily TASQ 0.25 mg/d escalating to 1.0 mg/d over 4 weeks or placebo. The primary end point was the proportion of patients without disease progression at 6 months, defined by Response Evaluation Criteria in Solid Tumors Group, Prostate Cancer Working Group (PCWG2), or pain criteria, excluding prostate-specific antigen. Results: Two hundred one men (134 assigned to TASQ; 67 to placebo) were evaluable, and baseline characteristics were well balanced. Six-month progression-free proportions for TASQ and placebo groups were 69% and 37%, respectively (P < .001), and median progression-free survival (PFS) was 7.6 versus 3.3 months (P = .0042). In PCWG2 CRPC clinical subgroups, PFS in months was as follows: nodal metastases, 6.1 versus 3.1; bone metastases, 8.8 versus 3.4; and visceral metastases, 6.0 versus 3.0 for patients receiving TASQ versus placebo, respectively. Bone alkaline phosphatase levels were stabilized in the TASQ group, whereas the impact on PSA kinetics was less pronounced. Adverse events (AEs) occurring more frequently in the TASQ arm included GI disorders, fatigue, musculoskeletal pains, and elevations of pancreatic and inflammatory biomarkers. Grade 3 to 4 AEs, including asymptomatic elevations of laboratory parameters, were reported in 40% of patients receiving TASQ versus 10% receiving placebo; deep vein thrombosis (4% v 0%) was more common in the TASQ arm. Conclusion: TASQ significantly slowed progression and improved PFS in patients with metastatic CRPC with an acceptable AE profile.
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| 2. |
- Armstrong, A J, et al.
(författare)
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Long-term Survival and Biomarker Correlates of Tasquinimod Efficacy in a Multicenter Randomized Study of Men with Minimally Symptomatic Metastatic Castration-Resistant Prostate Cancer.
- 2013
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Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 19:24, s. 6891-6901
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Tasquinimod (Active Biotech) is an oral immunomodulatory, anti-angiogenic, and anti-metastatic agent that delayed metastatic disease progression in a randomized placebo-controlled phase II trial in men with metastatic castration-resistant prostate cancer (mCRPC). Here, we report long-term survival with biomarker correlates from this trial.EXPERIMENTAL DESIGN: Two hundred and one (134 tasquinimod and 67 placebo) men with mCRPC were evaluated. Forty-one men randomized to placebo crossed over to tasquinimod. Survival data were collected with a median follow-up time of 37 months. Exploratory biomarker studies at baseline and over time were collected to evaluate potential mechanism-based correlates with tasquinimod efficacy including progression-free survival (PFS) and overall survival (OS).RESULTS: With 111 mortality events, median OS was 33.4 months for tasquinimod versus 30.4 months for placebo overall, and 34.2 versus 27.1 months in men with bone metastases (n = 136), respectively. Multivariable analysis demonstrated an adjusted HR of 0.52 [95% confidence interval (CI), 0.35-0.78; P = 0.001] for PFS and 0.64 (95% CI, 0.42-0.97; P = 0.034) for OS, favoring tasquinimod. Time-to-symptomatic progression was improved with tasquinimod (P = 0.039, HR = 0.42). Toxicities tended to be mild in nature and improved over time. Biomarker analyses suggested a favorable impact on bone alkaline phosphatase and lactate dehydrogenase (LDH) over time and a transient induction of inflammatory biomarkers, VEGF-A, and thrombospondin-1 levels with tasquinimod. Baseline levels of thrombospondin-1 less than the median were predictive of treatment benefit.CONCLUSIONS: The survival observed in this trial of men with minimally symptomatic mCRPC suggests that the prolongation in PFS with tasquinimod may lead to a survival advantage in this setting, particularly among men with skeletal metastases, and has a favorable risk:benefit ratio.
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| 3. |
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| 4. |
- Bill-Axelson, Anna, et al.
(författare)
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Radical prostatectomy versus watchful waiting in early prostate cancer.
- 2011
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Ingår i: The New England journal of medicine. - : Massachussetts Medical Society. - 1533-4406 .- 0028-4793. ; 364:18, s. 1708-17
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Forskningsöversikt (refereegranskat)abstract
- In 2008, we reported that radical prostatectomy, as compared with watchful waiting, reduces the rate of death from prostate cancer. After an additional 3 years of follow-up, we now report estimated 15-year results.
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| 5. |
- Wadström, Jonas, et al.
(författare)
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Laparoscopic nephropexy exposes a possible underlying pathogenic mechanism and allows successful treatment with tissue gluing of the kidney and fixation of the colon to the lateral abdominal wall
- 2010
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Ingår i: International Brazilian journal of urology : official journal of the Brazilian Society of Urology. - 1677-5538. ; 36:1, s. 10-17
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Surgical treatment of "Ren Mobilis" has historically been associated with poor results and fairly high morbidity. We have used a transperitoneal laparoscopic approach in order to minimize morbidity. The goal of this study was to evaluate the success rate and to discuss the possible pathogenic mechanism, which has implications for the surgical strategy. MATERIALS AND METHODS: Seven women with a right mobile kidney were examined by intravenous pyelogram and CT scans. Symptoms were judged to emanate from the mobile kidney. Transperitoneal laparoscopic nephropexy was performed. The surgical treatment consisted of fixing the kidney to the dorsal abdominal wall using tissue glue (Tisseel) after diathermy coagulation of the surfaces to induce fibrosis. The right colon was fixed with clips to the lateral abdominal wall, trapping the kidney in place. RESULTS: In 6 of the cases, there was an incomplete rotation of the ascending colon to the right side, allowing the kidney to move freely. In one case, the kidney moved into a retroperitoneal pocket of the mesocolon. The 6 cases with a lateral passage for the kidney were symptom-free at follow-up (30-80 months), but in the 7th case the patient's kidney quickly loosened and she underwent an open reoperation, after which she was symptom-free. CONCLUSION: Our series demonstrates that good results can be achieved with a transperitoneal laparoscopic approach, but also indicates that there is a common pathogenic mechanism with incomplete rotation of the ascending colon that can be corrected during surgery, which might contribute to the good results.
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| 6. |
- Weis, Jan, et al.
(författare)
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MR spectroscopy of the human prostate using surface coil at 3 T : Metabolite ratios, age-dependent effects, and diagnostic possibilities
- 2011
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Ingår i: Journal of Magnetic Resonance Imaging. - : Wiley. - 1053-1807 .- 1522-2586. ; 34:6, s. 1277-1284
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To measure prostate spectra of healthy volunteers using a surface coil, to demonstrate age-dependent effects, and to investigate diagnostic possibilities for prostate cancer detection. MATERIALS AND METHODS: Single-voxel and 2D magnetic resonance spectroscopic imaging (MRSI) spectra of 51 healthy volunteers with biopsy-proven prostate carcinoma of 20 patients for comparison were measured and processed using the LCModel. The mean normalized spectra and mean metabolite-to-citrate intensity ratios were computed. RESULTS: Metabolite-to-citrate ratios of healthy volunteers were lower in the older group (>51 years) than in the younger group (<45 years). The peripheral zone (PZ) revealed a lower metabolite-to-citrate intensity ratio than the central gland (CG). Age-related differences in metabolite-to-citrate ratio were insignificant in the voxels with predominantly CG tissue, whereas significant differences were found in the PZ. Sensitivity in detecting prostate cancer by single-voxel spectroscopy (SVS) and 2D MRSI was 75% and 80%, respectively. CONCLUSION: SVS and 2D MRSI of the prostate at 3 T, using a surface coil, are useful in situations when insertion of the endorectal coil into the rectum is difficult or impossible. Our findings of age-dependent effects may be of importance for the analysis of patient spectra.
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