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- Sartor, Oliver, et al.
(författare)
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Effect of radium-223 dichloride on symptomatic skeletal events in patients with castration-resistant prostate cancer and bone metastases : results from a phase 3, double-blind, randomised trial
- 2014
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Ingår i: The Lancet Oncology. - 1470-2045 .- 1474-5488. ; 15:7, s. 738-746
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Tidskriftsartikel (refereegranskat)abstract
- Background Bone metastases frequently cause skeletal events in patients with metastatic castration-resistant prostate cancer. Radium-223 dichloride (radium-223) selectively targets bone metastases with high-energy, short-range a-particles. We assessed the effect of radium-223 compared with placebo in patients with castration-resistant prostate cancer and bone metastases. Methods In this phase 3, double-blind, randomised ALSYMPCA trial, we enrolled patients who had symptomatic castration-resistant prostate cancer with two or more bone metastases and no known visceral metastases, who were receiving best standard of care, and had previously either received or were unsuitable for docetaxel. Patients were stratified by previous docetaxel use, baseline total alkaline phosphatase level, and current bisphosphonate use, then randomly assigned (2: 1) to receive either six intravenous injections of radium-223 (50 kBq/kg) or matching placebo; one injection was given every 4 weeks. Randomisation was done with an interactive voice response system, taking into account trial stratification factors. Participants and investigators were masked to treatment assignment. The primary endpoint was overall survival, which has been reported previously. Here we report on time to first symptomatic skeletal event, defined as the use of external beam radiation to relieve bone pain, or occurrence of a new symptomatic pathological fracture (vertebral or non-verterbal), or occurence of spinal cord compression, or tumour-related orthopeadic surgical intervention. All events were required to be clinically apparent and were not assessed by periodic radiological review. Statistical analyses of symptomatic skeletal events were based on the intention-to-treat population. The study has been completed and is registered with ClinicalTrials.gov, number NCT00699751. Findings Between June 12, 2008, and Feb 1, 2011, 921 patients were enrolled, of whom 614 (67%) were randomly assigned to receive radium-223 and 307 (33%) placebo. Symptomatic skeletal events occurred in 202 (33%) of 614 patients in the radium-223 group and 116 (38%) of 307 patients in the placebo group. Time to first symptomatic skeletal event was longer with radium-223 than with placebo (median 15.6 months [95% CI 13.5-18.0] vs 9.8 months [7.3-23.7]; hazard ratio [HR] = 0.66, 95% CI 0.52-0.83; p = 0.00037). The risks of external beam radiation therapy for bone pain (HR 0.67, 95% CI 0.53-0.85) and spinal cord compression (HR = 0.52, 95% CI 0.29-0.93) were reduced with radium-233 compared with placebo. Radium-223 treatment did not seem to significantly reduce the risk of symptomatic pathological bone fracture (HR 0.62, 95% CI 0.35-1.09), or the need for tumour-related orthopaedic surgical intervention (HR 0.72, 95% CI 0.28-1.82). Interpretation Radium-223 should be considered as a treatment option for patients with castration-resistant prostate cancer and symptomatic bone metastases.
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| 2. |
- Abouassaly, Robert, et al.
(författare)
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Sequelae of Treatment in Long-term Survivors of Testis Cancer
- 2011
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Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 60:3, s. 516-526
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Forskningsöversikt (refereegranskat)abstract
- Context: Testicular cancer patients are often diagnosed at a young age, and because of the advances in the treatment of this disease, the vast majority have a normal life expectancy after therapy. Thus, recognition of the long-term sequelae of treatment (ie, surgery, radiation therapy, and chemotherapy) is particularly important in these patients. Objective: To review the adverse effects and the risk of secondary malignancy in long-term survivors of testicular cancer. Evidence acquisition: We conducted a Medline search to identify original articles and reviews on the long-term effects of testicular cancer treatment. Although the search included articles from January 1948 to February 2011, the majority of the included articles were published in the last two decades. Evidence synthesis: All studies examining the long-term sequelae of treatment in testicular cancer are retrospective in nature, with most classified as cohort, case-control, and/or epidemiologic studies. Given that no standardized method of reporting long-term complications exists, evidence synthesis is limited. Conclusions: Recent evidence suggests an increased risk of cardiovascular disease, neurotoxicity, and mild reductions in renal function in survivors of testicular cancer. Treatment of testicular malignancy can also negatively affect gonadal function and fertility and has been shown to result in an increased risk of solid malignancy and leukemia. (C) 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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| 3. |
- Dahl, Christian Falk, et al.
(författare)
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A controlled study of risk factors for disease and current problems in long-term testicular cancer survivors
- 2010
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Ingår i: Journal of cancer survivorship. - : Springer Science and Business Media LLC. - 1932-2259 .- 1932-2267. ; 4:3, s. 256-265
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Tidskriftsartikel (refereegranskat)abstract
- Introduction To compare risk factors for disease and current problems in long-term testicular cancer survivors (TCSs) and age-matched population-based controls (NORMs). Methods The study was cross-sectional and concerned 1,291 Norwegian TCSs followed up after a mean of 11 years, and 6,455 NORMs. Both TCSs and NORMs completed questionnaires and had a clinical examination. Indices for risk factors and current problems were calculated. Outcome measures were: visits to general practitioners last year, poor self-rated health, and poor quality of life (QoL). Results The mean risk score was significantly lower and the mean current problem score significantly higher in TCSs compared to NORMs without reaching clinical significance. The risk for future fatal cardiac events did not differ between the groups. TCSs had a higher risk for visiting a general practitioner than NORMs (OR 3.58, 95% CI 3.09-4.15), while no significant difference was observed for self-rated health. Poor QoL in TCSs was significantly associated with more current problems than risk factors. Previous treatment for mental problems, presence of severe somatic disease and musculo-skeletal problems were significantly associated with all three outcome measures. Musculo-skeletal problems were most strongly associated with visits to general practitioners among TCSs. Conclusions Several risk factors for preventive clinical interventions and current problems that eventually should be treated were identified in TCSs. Implications for cancer survivors TCSs show several risk factors and current problems that are relevant for visits to general practitioners, poorer self-rated health, and poorer QoL. These should get attention from health personnel caring for TCSs.
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| 4. |
- Fossa, Sophie D., et al.
(författare)
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Ten-and 15-year prostate cancer-specific survival in patients with nonmetastatic high-risk prostate cancer randomized to lifelong hormone treatment alone or combined with radiotherapy (SPCG VII)
- 2014
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Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 32:4
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: After a median observation time of 7.6 years, Scandinavian Prostate Cancer Group VII randomized trial showed a significant 12% reduction of prostate cancer-specific mortality in patients with locally advanced or histologically aggressive prostate cancer who received three months of total androgen blockade followed by radiotherapy and continuous antiandrogen therapy compared to patients with hormonal treatment only (Widmark et al :Lancet [2009]; 373,1174). Here we provide the 10 (15)-year survival results after a median observation time of 10.7 years. Methods: Between February 1996 and December 2002, 875 patients with locally advanced prostate cancer were randomized (Randomization ratio 1:1). Primary endpoint was prostate cancer-specific survival analyzed by intention to treat. This updated analysis is based on death registry data of the Norwegian patients (2/3 of the population), and on data recorded in CRF database available for the Swedish patients. A Swedish death registry analysis is underway, and will be included in the final analysis at the meeting. Results: Prostate cancer death occurred in 118 out of 439 of the antiandrogen treatment group and in 45 out of 436 men in the combination treatment group (p< 0.0001), with death due to any cause in 210 out of 439 and 161 out of 436 men (p=0.0006), respectively. The 10 (15) year cumulative prostate cancer-specific mortality was more than halved after combined treatment: 18.9% (30.7%) and 8.3% (12.4%) (HR=0.35;[p<4.1E-10 for 15 year results]), and overall mortality was 35.3% (56.7%) and 26.4% (43.4%) (HR=0.70; P=0.0006 for 15 year results), respectively. Conclusions: Addition of local radiotherapy to hormonal treatment in patients with non-metastatic locally advanced or high-risk prostate cancer more than halved the 10 and 15 year prostate cancer-specific mortality and substantially decreased overall mortality.
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