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- Nilsson, S., et al.
(författare)
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Bone-targeted radium-223 in symptomatic, hormone-refractory prostate cancer: a randomised, multicentre, placebo-controlled phase II study
- 2007
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Ingår i: Lancet Oncol. - 1470-2045 .- 1474-5488. ; 8:7, s. 587-594
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The alpha-emitter radium-223 ((223)Ra) is a bone-seeking radionuclide studied as a new treatment for patients with bone metastases from hormone-refractory prostate cancer. We aimed to study mature outcomes from a randomised, multicentre, phase II study of (223)Ra. METHODS: Patients with hormone-refractory prostate cancer and bone pain needing external-beam radiotherapy were assigned to four intravenous injections of (223)Ra (50 kBq/kg, 33 patients) or placebo (31 patients), given every 4 weeks. Primary endpoints were change in bone-alkaline phosphatase (ALP) concentration and time to skeletal-related events (SREs). Secondary endpoints included toxic effects, time to prostate-specific-antigen (PSA) progression, and overall survival. All tests were done at a 5% significance level, based on intention to treat. FINDINGS: Median relative change in bone-ALP during treatment was -65.6% (95% CI -69.5 to -57.7) and 9.3% (3.8-60.9) in the (223)Ra group and placebo groups, respectively (p<0.0001, Wilcoxon ranked-sums test). Hazard ratio for time to first SRE, adjusted for baseline covariates, was 1.75 (0.96-3.19, p=0.065, Cox regression). Haematological toxic effects did not differ significantly between two groups. No patient discontinued (223)Ra because of treatment toxicity. Median time to PSA progression was 26 weeks (16-39) versus 8 weeks (4-12; p=0.048) for (223)Ra versus placebo, respectively. Median overall survival was 65.3 weeks (48.7-infinity) for (223)Ra and 46.4 weeks (32.1-77.4) for placebo (p=0.066, log rank). The hazard ratio for overall survival, adjusted for baseline covariates was 2.12 (1.13-3.98, p=0.020, Cox regression). INTERPRETATION: (223)Ra was well tolerated with minimum myelotoxicity, and had a significant effect on bone-ALP concentrations. Larger clinical trials are warranted to study (223)Ra on the prevention of SREs and on overall survival in patients with hormone-refractory prostate cancer. Bone-targeting properties of (223)Ra could also potentially be used for treating skeletal metastasis from other primary cancers.
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| 4. |
- Ullen, A., et al.
(författare)
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Additive/synergistic antitumoral effects on prostate cancer cells in vitro following treatment with a combination of docetaxel and zoledronic acid
- 2005
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Ingår i: Acta Oncol. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 44:6, s. 644-50
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Tidskriftsartikel (refereegranskat)abstract
- Once bone metastasized and androgen independent, prostate cancer is often associated with skeletal morbidity and disability. New treatment modalities that can palliate symptoms from the skeleton and inhibit further progression are warranted. In this study, the antitumoral effects following treatment with a combination of docetaxel and the new generation bisphosphonate, zoledronic acid, were investigated on two hormone-refractory prostate cancer cell lines: PC3 and DU145. The prostate cancer cells were treated with increasing concentrations of zoledronic acid in the absence or presence of docetaxel. Toxicity was measured using fluorometric microculture cytotoxic assay technique. A concentration of 25 microM, zoledronic acid reduced the viable cell number to 68% and 98% for PC3 and DU145 cells respectively. Docetaxel, on the other hand, at a concentration of 0.1 ng/ml, had no effect on the viability. However, a combination of zoledronic acid and docetaxel reduced the cell number to 60% and 81% respectively. Furthermore, zoledronic acid in the concentration range 12.5 microM-50 microM enhanced the antitumoral effects of docetaxel (0.01-1 ng/ml) in an additive and/or synergistic manner for both cell lines. These data support the hypothesis that zoledronic acid, in addition to having bone resorption inhibiting properties, also exhibits anti-tumoral effects. It also appears that combined treatment with docetaxel causes additive and/or synergistic cytostatic effects on prostate cancer cells.
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- Ullen, A., et al.
(författare)
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Prostate cancer cell lines lack amplification: overexpression of HER2
- 2005
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Ingår i: Acta Oncol. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 44:5, s. 490-5
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Tidskriftsartikel (refereegranskat)abstract
- The potential overexpression of HER2 in prostate cancer cells has attended significant interest during the past few years, both as potential target for HER2 pathway focused therapy and as a mechanism involved in the progression to androgen independence. Conflicting results have been reported concerning HER2 status on clinical material, differences which generally have been attributed to methodological differences. Nevertheless, HER2 has been utilized for targeted therapy of prostate cancer in a number of preclinical studies and is still regarded as an exciting target molecule. In this study, the HER2 status of three widely used prostate cancer cell lines and corresponding xenografts has been analysed. By use of validated and FDA approved analytical staining techniques none of these cell lines or xenografts were shown to overexpress/amplify HER2, as demonstrated by immunohistochemistry and fluorescence in situ hybridization. These findings are important for the interpretation and understanding of the therapeutic effects when developing drugs targeting HER2 in prostate cancer cell lines and also emphasize the importance of using broad and validated analytical techniques.
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