醫(yī)藥新知【50】

1、醫(yī)藥新知【50】公告日期: 摘錄藥師: 林佩怡¡ 主題: Longer Infusion Times for Anthracyclines Reduce Cardiac Damage 以較長時間輸注Anthracyclines降低心臟損傷¡ 內(nèi)容摘要:November 29, 2006 Using a longer infusion time for anthracycline administration may reduce the cardiotoxicity of these drugs, suggests a new Cochrane review. "

2、An anthracycline infusion duration of 6 hours or longer reduces the risk of clinical heart failure, and it seems to reduce the risk of subclinical cardiac damage," the authors conclude.Anthracycline-induced cardiotoxicity appears to be related to the peak plasma drug concentration, while the an

3、titumor activity depends on tissue concentration over time, lead researcher Elvira van Dalen, MD, from the Emma Children's Hospital, in Amsterdam, the Netherlands, explained to Medscape. Prolonging the infusion time reduces the peak anthracycline concentration, with potentially less cardiotoxici

4、ty, while maintaining the antitumor activity, she said. Significant Reduction in Clinical Heart Failure The authors conducted a meta-analysis of 6 randomized clinical trials, involving a total of 625 patients. The majority of patients were adults with different types of solid tumors, and the drugs u

5、sed were doxorubicin, daunorubicin, and epirubicin.Results from 5 trials (n = 557) showed that patients who received an infusion over a 6-hour period or longer had a significantly lower rate of clinical heart failure than patients who received infusions of shorter duration (lasting 1 hour or less).

6、The risk was around 75% lower in patients receiving the longer infusions compared with the shorter infusions (relative risk, 0.27; 95% CI 0.09 0.81).Results from 2 individual trials suggest that the longer infusion time also reduces the risk of subclinical cardiac damage ?the various cardiac abnorma

7、lities diagnosed with, for example, echocardiography in asymptomatic patients.The duration of the infusion did not appear to affect either tumor response or overall survival, the researchers report. The prolonged infusion of 6 hours or more might be justified in patients who are at high risk of card

8、iac damage or patients who need a high cumulative dose of chemotherapy, the authors conclude. However, in comments to Medscape, Dr. van Dalen added: "Recommendations for clinical practice should be made by clinicians who should weigh all the available evidence, not only on cardiotoxicity but al

9、so on antitumor efficacy and other adverse effects." Further Studies in Children Needed The researchers emphasize that most of the patients in these studies were adults with advanced solid tumors, and very few children were included. "Since there is only a small amount of data for children

10、 and because data obtained in adults cannot be extrapolated to children, different anthracycline infusion durations should be evaluated further in children," they comment. No adequate studies in children with solid tumors are available, Dr. van Dalen noted, although there are 2 trials in childr

11、en with leukemia. In these 2 trials, no difference was seen in the cardiac damage with different infusion durations, and there was no information on antitumor efficacy, she said. Differences Between Anthracycline Derivatives A second Cochrane review by the same group of authors investigated whether

12、the anthracycline derivatives differed in their potential for cardiotoxicity. There is some suggestion of a lower rate of clinical heart failure with epirubicin compared with doxorubicin, they comment, although the difference was not significant. This analysis was based on 5 trials involving 1036 pa

13、tients. "We are not able to favor either epirubicin or doxorubicin when given at the same dose," they conclude. However, there is evidence to favor liposomal-encapsulated doxorubicin over conventional doxorubicin in adults with solid tumors, they note. In an analysis of 2 trials involving

14、521 patients, the liposomal-encapsulated drug was associated with a significantly lower rate of clinical heart failure than the conventional product (RR, 0.20; 95% CI, 0.05 ?0.75).中文摘要:November 29, 2006 根據(jù)一項新的Cochrane回顧性文章，以較長anthracycline可能降低這些藥物的心臟毒性。作者表示，以6個小時以上的輸注時間注射anthracycline，可以降低發(fā)生臨床心臟衰竭的風

15、險，而且似乎可以降低臨床心臟損傷的風險。主要作者荷蘭阿姆斯特丹Emma 兒童醫(yī)院Elvira van Dalen醫(yī)師表示，Anthracycline類藥物引起的心臟毒性顯然與最高血中濃度有關(guān)，且其抑制腫瘤效力與組織中濃度有關(guān)；她表示，較長的輸注時間可以降低anthracycline濃度，使心臟毒性降低，且維持抗腫瘤活性?！撅@著降低臨床心臟衰竭】作者進行一項收納6個隨機分派臨床試驗的綜合分析，共有625位病患；主要的病患為罹患不同形式固體腫瘤的成人，使用的藥物包括doxorubicin、daunorubicin與epirubicin。收集五項臨床數(shù)據(jù)（共有557位）顯示，接受持續(xù)輸注6個小時以上

16、的病患發(fā)生臨床心臟衰竭風險，相較於輸注時間較短病患（少於1個小時）低，接受較長時間輸注病患相較於較短輸注時間風險大約下降75%（相對風險為；95%信賴區(qū)間為）。根據(jù)兩項各自臨床試驗，輸注時間較長也降低臨床心臟損傷，舉例來說，以無癥狀病患的心臟超音波來診斷不同心臟異常。作者表示，輸注時間顯然不會影響抑制腫瘤活性或是整體存活率。作者的結(jié)論是，延長輸注時間超過6個小時可能適用於高心臟損傷風險病患、或是需要高累積劑量化學療法病患；然而，van Dalen醫(yī)師向Medscape表示，臨床治療的建議應該由醫(yī)師權(quán)衡所有目前的證據(jù)，而不是僅根據(jù)心臟毒性，還要兼顧抑制腫瘤活性與其他不良反應?！疚磥硇枰獌和难芯?/p>

17、】作者強調(diào)，這些研究中大部分的病患是罹患進展性固體腫瘤的成人，僅有少數(shù)兒童病患；由於兒童相關(guān)數(shù)據(jù)並不多，且因為成人病患數(shù)據(jù)不能延伸應用在兒童身上，應該針對兒童病患進行不同anthracycline輸注時間的研究。van Dalen醫(yī)師表示，目前並沒有足夠罹患固體腫瘤兒童病患的資料，雖然有兩項白血病兒童研究；但她表示，這兩項研究中，不同輸注時間引起的心臟損傷並沒有差異，且沒有相關(guān)抑制腫瘤活性資料?！静煌珹nthracycline類藥物之間的差異】同樣一群作者的另一篇Cochrane回顧性文章中，研究anthracycline相似物在心臟損傷方面是否有差異。她表示，有部份意見表示epirubicin引起臨床心臟衰竭的風險比doxorubicin低，雖然其差異並不顯著；這項研究根據(jù)五項臨床試驗，共有1036位病患，作者的結(jié)論是，當以同樣