거세저항성 전립선암 환자의 치료 편집하기 (부분)

==근거표==
{| class="wikitable"
!KQ18
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!Reference
|1. Saad F, Gleason DM, Murray R, Tchekmedyian S, Venner P, Lacombe L, et al. A randomized, placebo-controlled trial of zoledronic acidin patients with hormone-refractory metastatic prostate carcinoma. J Natl Cancer Inst 2002;94:1458-68.
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!Study type
|Randomized controlled trial
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!Patients
|Zoledronic acid at 4 mg (N=214), zoledronic acid at 8 mg (subsequently reduced to 4 mg; 8/4) (N=221), or placebo (N=208)
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!Purpose of Study
|To studied the effect of a new bisphosphonate, zoledronic acid, which blocks bone destruction, on skeletal complications in prostate cancer patients with bone metastases
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!Study Results
|Approximately 38% of patients who received zoledronic acid at 4 mg, 28% who received zoledronic acid at 8/4 mg, and 31% who received placebo completed the study. A greater proportion of patients who received placebo had skeletal-related events than those who received zoledronic acid at 4 mg (44.2% versus 33.2%; difference=-11.0%, 95% confidence interval [CI]=-20.3% to -1.8%; P=.021) or those who received zoledronic acid at 8/4 mg (38.5%; difference versus placebo=-5.8%, 95% CI=-15.1% to 3.6%; P=.222). Median time to first skeletal-related event was 321 days for patients who received placebo, was not reached for patients who received zoledronic acid at 4 mg (P=.011 versus placebo), and was 363 days for those who received zoledronic acid at 8/4 mg (P=.491 versus placebo). Compared with urinary markers in patients who received placebo, urinary markers of bone resorption were statistically significantly decreased in patients who received zoledronic acid at either dose (P=.001). Pain and analgesic scores increased more in patients who received placebo than in patients who received zoledronic acid, but there were no differences in disease progression, performance status, or quality-of-life scores among the groups. Zoledronic acid at 4 mg given as a 15-minute infusion was well tolerated, but the 8-mg dose was associated with renal function deterioration.
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!Level of Study
|1
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!Reference
|2. Saad F, Gleason DM, Murray R, Tchekmedyian S, Venner P, Lacombe L ,et al. Long-term efficacy of zoledronic acid for the prevention of skeletal complications in patients with metastatic hormone-refractory prostate cancer. J Natl Cancer Inst 2004;96:879-82.
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!Study type
|Randomized controlled trial
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!Patients
|Zoledronic acid at 4 mg (N=214), zoledronic acid at 8 mg (subsequently reduced to 4 mg; 8/4) (N=221), or placebo (N=208)
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!Purpose of Study
|To examine long-term efficacy of zoledronic acid for the prevention of skeletal complications in patients with metastatic hormone-refractory prostate cancer.
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!Study Results
|Among 122 patients who completed a total of 24 months on study, fewer patients in the 4-mg zoledronic acid group than in the placebo group had at least one SRE (38% versus 49%, difference=-11.0%, 95% confidence interval [CI]=-20.2% to -1.3%; P=.028), and the annual incidence of SREs was 0.77 for the 4-mg zoledronic acid group versus 1.47 for the placebo group (P=.005). The median time to the first SRE was 488 days for the 4-mg zoledronic acid group versus 321 days for the placebo group (P=.009). Compared with placebo, 4 mg of zoledronic acid reduced the ongoing risk of SREs by 36% (risk ratio=0.64, 95% CI=0.485 to 0.845; P=.002). Patients in the 4-mg zoledronic acid group had a lower incidence of SREs than did patients in the placebo group, regardless of whether they had an SRE prior to entry in the study. Long-term treatment with 4 mg of zoledronic acid is safe and provides sustained clinical benefits for men with metastatic hormone-refractory prostate cancer.
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!Level of Study
|1
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!Reference
|3. Aapro M, Abrahamsson PA, Body JJ, Coleman RE, Colomer R, Costa L, et al. Guidance on the use of bisphosphonates in solid tumours: recommendations of an international expert panel. Ann Oncol 2008;19:420-32.
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!Study type
|Review article
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!Patients
|Review article
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!Purpose of Study
|The purpose of this paper is to review the current evidence on the use of BP in solid tumours and provide clinical recommendations
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!Study Results
|Based on available evidence, the panel recommends amino-bisphosphonates for patients with metastatic bone disease from breast cancer and zoledronic acid for patients with other solid tumours as primary disease. Dosing of BP should follow approved indications with adjustments if necessary. While i.v. administration is most often preferable, oral administration (clodronate, IBA) may be considered for breast cancer patients who cannot or do not need to attend regular hospital care. Early-stage cancer patients at risk of developing CTIBL should be considered for preventative BP treatment. The strongest evidence in this setting is now available for ZOL. Overall, BP are well-tolerated, and most common adverse events are influenza-like syndrome, arthralgia, and when used orally, gastrointestinal symptoms. The dose of BP may need to be adapted to renal function and initial creatinine clearance calculation is mandatory according to the panel for use of any BP. Subsequent monitoring is recommended for ZOL and PAM, as described by the regulatory authority guidelines. Patients scheduled to receive BP (mainly every 3-4 weeks i.v.) should have a dental examination and be advised on appropriate measures for reducing the risk of jaw osteonecrosis. BP are well established as supportive therapy to reduce the frequency and severity of skeletal complications in patients with bone metastases from different cancers.
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!Level of Study
|6
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!Reference
|4. Fizazi K, Carducci M, Smith M, Damião R, Brown J, Karsh L, et al. Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. Lancet 2011;377:813-22.
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!Study type
|Randomized controlled trial
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!Patients
|1,904 patients were randomised, of whom 950 assigned to denosumab and 951 assigned to receive zoledronic acid
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!Purpose of Study
|To compare denosumab, a human monoclonal antibody against RANKL, with zoledronic acid for prevention of skeletal-related events in men with bone metastases from castration- resistant prostate cancer
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!Study Results
|Median duration on study at primary analysis cutoff date was 12.2 months (IQR 5.9-18.5) for patients on denosumab and 11.2 months (IQR 5.6-17.4) for those on zoledronic acid. Median time to first on-study skeletal-related event was 20.7 months (95% CI 18.8-24.9) with denosumab compared with 17.1 months (15.0-19.4) with zoledronic acid (hazard ratio 0.82, 95% CI 0.71-0.95; p=0.0002 for non-inferiority; p=0.008 for superiority). Adverse events were recorded in 916 patients (97%) on denosumab and 918 patients (97%) on zoledronic acid, and serious adverse events were recorded in 594 patients (63%) on denosumab and 568 patients (60%) on zoledronic acid. More events of hypocalcaemia occurred in the denosumab group (121 [13%]) than in the zoledronic acid group (55 [6%]; p<0.0001). Osteonecrosis of the jaw occurred infrequently (22 [2%] vs 12 [1%]; p=0.09).
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!Level of Study
|I
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!Reference
|5. Smith MR, Saad F, Coleman R, Shore N, Fizazi K, Tombal B, et al. Denosumab and bone- metastasis-free survival in men with castration-resistant prostate cancer: results of a phase 3, randomised, placebo-controlled trial. Lancet 2012;379:39-46.
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!Study type
|Randomized controlled tria
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!Patients
|1,432 patients were randomly assigned to treatment groups (716 denosumab, 716 placebo).
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!Purpose of Study
|To assess denosumab, a fully human anti-RANKL monoclonal antibody, for prevention of bone metastasis or death in non-metastatic castration-resistant prostate cancer.
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!Study Results
|Denosumab significantly increased bone-metastasis-free survival by a median of 4.2 months compared with placebo (median 29.5 [95% CI 25.4-33.3] vs 25.2 [22.2- 29.5] months; hazard ratio [HR] 0.85, 95% CI 0.73-0.98, p=0.028). Denosumab also significantly delayed time to first bone metastasis (33.2 [95% CI 29.5-38.0] vs 29.5 [22.4- 33.1] months; HR 0.84, 95% CI 0.71-0.98, p=0.032). Overall survival did not differ between groups (denosumab, 43.9 [95% CI 40.1-not estimable] months vs placebo, 44.8 [40.1-not estimable] months; HR 1.01, 95% CI 0.85-1.20, p=0.91). Rates of adverse events and serious adverse events were similar in both groups, except for osteonecrosis of the jaw and hypocalcaemia. 33 (5%) patients on denosumab developed osteonecrosis of the jaw versus none on placebo. Hypocalcaemia occurred in 12 (2%) patients on denosumab and two (<1%) on placebo.
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!Level of Study
|I
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!Reference
|6. Macherey S, Monsef I, Jahn F, Jordan K, Yuen KK, Heidenreich A, Skoetz N. Bisphosphonates for advanced prostate cancer. Cochrane Database Syst Rev 2017;12.
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!Study type
|Meta-Analysis Research
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!Patients
|We identified studies by electronic search of bibliographic databases including the Cochrane Controlled Trials Register and MEDLINE on 13 July 2017 and trial registries. We handsearched the Proceedings of American Society of Clinical Oncology (to July 2017) and reference lists of all eligible trials identified. This is an update of a review last published in 2006.
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!Purpose of Study
|To assess the effects of bisphosphonates in men with bone metastases from prostate cancer.
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!Study Results
|PRIMARY OUTCOME: there was no clear difference in the proportion of participants with pain response (RR 1.15, 95% CI 0.93 to 1.43; P=0.20; I2=0%; 3 trials; 876 participants; low quality evidence). In absolute terms, bisphosphonates resulted in a pain response in 40 more participants per 1000 (19 fewer to 114 more). SECONDARY OUTCOMES: bisphosphonates probably reduced the incidence of skeletal-related events in participants with prostate cancer metastatic to bone (RR 0.87, 95% CI 0.81 to 0.94; P=0.27; I2=19%; 9 trials; 3153 participants; moderate quality evidence). In absolute terms, bisphosphonates resulted in 58 fewer SREs per 1000 (85 fewer to 27 fewer).We found no clinically relevant differences in mortality (RR 0.97, 95% CI 0.91 to 1.04; P=0.43; I2=1%; 9 trials; 2450 participants; moderate quality evidence). In absolute terms, bisphosphonates resulted in 16 fewer deaths per 1000 (47 fewer to 21 more).Outcome definition of quality of life and the measurement tools varied greatly across trials and we were unable to extract any quantitative data for meta-analysis.Bisphosphonates probably increased the number of participants affected by nausea (RR 1.19, 95% CI 1.00 to 1.41; P=0.05; I2=0%; 9 trials; 3008 participants; moderate quality evidence). In absolute terms, bisphosphonates resulted in seven more cases of nausea per 1000 (0 fewer to 14 more). Bisphosphonates probably increased the number of renal adverse events (RR 1.65, 95% CI 1.11 to 2.46; P=0.01; I2=0%; 7 trials; 1794 participants; moderate quality evidence). In absolute terms, bisphosphonates resulted in 22 more renal adverse events per 1000 (4 more to 50 more). We found no clear difference in the number of participants with osteonecrosis of the jaw between groups (RR 1.92, 95% CI 0.75 to 4.90; P=0.17; I2=0%; 5 trials; 1626 participants; very low quality evidence). In absolute terms, bisphosphonates resulted in seven more cases with osteonecrosis of the jaw per 1000 (2 fewer to 29 more). We observed no clinically relevant difference in the proportion of participants with decreased analgesic consumption (RR 1.19, 95% CI 0.87 to 1.63; P=0.28; I2=37%; 4 trials; 416 participants). Statistical analysis revealed that bisphosphonates probably reduced the number of participants with disease progression (RR 0.94, 95% CI 0.90 to 0.98; P=0.006; I2=0%; 7 trials; 2115 participants; moderate quality evidence). In absolute terms, bisphosphonates resulted in 36 fewer cases of disease progression per 1000 (71 fewer to 7 fewer).Findings of our predefined subgroup and sensitivity analyses were no different from those of the primary analyses.
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!Level of Study
|1
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