作者：Zosia Chustecka
出處：WebMD醫學新聞
September 18, 2008(瑞典斯德哥爾摩)－西班牙馬拉加Virgen de la Victoria醫院的Emilio Alba醫師表示，聚乙烯二醇化微脂粒doxorubicin (PLD；Caelyx，Schering-Plough藥廠)提供第一線anthracycline/taxane併用治療有反應之轉移乳癌婦女患者一項低毒性的維持治療選擇。
在155名病患的第三期研究中，相較於僅觀察者，PLD顯著延長無惡化存活；Alba 醫師等人在第33屆歐洲腫瘤醫學研討會中發表結果。使用PLD後到發生惡化的時間平均為13.18個月，只有觀察者的則是10.06個月(P= .0005)，12個月時的臨時分析顯示，使用PLD的病患有81%仍然存活，觀察組只有66% (P= .04)。
Alba醫師在聲明中表示，我們的試驗確認PLD維持治療有效且安全，是轉移乳癌病患有效的治療策略，因為它可延遲疾病惡化；他表示，根據這些結果，第一線治療之後使用PLD維持，未來將會成為西班牙研究團體(GEICAM)所進行之試驗的標準組。
Alba醫師在訪問中向Medscape Oncology表示，此產品也可在臨床上如此使用；目前，許多對第一線治療有反應的轉移乳癌婦女並未被給予維持治療；如果情況適合的話，有些醫師提供荷爾蒙治療，例如芳香胺酶抑制劑或者tamoxifen，有些醫師提供標靶治療，例如trastuzumab (Herceptin，羅氏藥廠)；他表示，但是，在很多時候，醫師沒有提供任何方式，這些結果認為，可以提供PLD作為一個選項，如同他們在試驗中進行的。
這種方法不屬於現有的產品適應症，歐洲核准PLD用於轉移乳癌且心臟風險增加之患者的單一療法，每4週劑量 50 mg/m2 。
在這個試驗中，PLD作為第一線anthracycline/taxane併用治療有反應之轉移乳癌婦女患者的維持治療，使用的劑量略低於每4週劑量 50 mg/m2 ，治療共有6個療程；研究者解釋，研究規範降低劑量是為了維持血液反應。
Alba醫師表示，試驗中看來，毒性相當低，這是主要發現之一；降低劑量的PLD與任何胃腸到毒性無關，沒有等級4禿頭或者等級4噁心和嘔吐，沒有心臟毒性(左心室射出分率沒有增加、臨床鬱血性心衰竭)；使用PLD的病患，有4%出現等級3/4手足症狀，其他等級3/4毒性不明顯、且在治療組和觀察組相似。
Alba醫師表示，之前轉移乳癌的化療維持治療試驗也顯示延緩惡化時間，有時候比整體存活長，但主要缺點是毒性；他表示，在這類患者，治療不是為了痊癒，重點在於獲得所有可行的方式。
他表示，維持治療對每個人幾乎都是好選項，如果我們可以設計毒性資料安全的有效治療，我認為使用聚乙烯二醇化微脂粒doxorubicin可以達成此目標。
第33屆歐洲腫瘤醫學 (ESMO) 研討會：摘要 145P。發表於2008年9月15日。
PEG-Liposomal Doxorubicin Useful for Maintenance Therapy in Metastatic Breast Cancer
By Zosia Chustecka
Medscape Medical News
September 18, 2008 (Stockholm, Sweden) ?Pegylated-liposomal doxorubicin (PLD; Caelyx, Schering-Plough) offers a low-toxicity option for maintenance therapy in women with metastatic breast cancer who have already responded to first-line treatment with an anthracycline/taxane combination, said Emilio Alba, MD, from the Hospital Virgen de la Victoria, in Maga, Spain.
PLD significantly prolonged progression-free survival, compared with observation alone, in a phase?3 study of 155 patients. Dr. Alba and his colleagues presented the results here at the 33rd European Society for Medical Oncology Congress. Time to progression was 13.18 months with PLD, and 10.06 months with observation (P?= .0005). A nonplanned analysis at 12 months showed that 81% of patients on PLD were still alive, compared with 66% in the observation group (P?= .04)
"Our trial confirms that PLD maintenance therapy, with its proven efficacy and significantly improved safety profile, can be a highly effective treatment strategy for patients with metastatic breast cancer, [because it delays] disease progression," Dr. Alba commented in a statement. Based on these results, he said, PLD maintenance after response to first-line therapy will be the standard group in all future trials conducted by the Spanish research group Grupe Espanol de Investigacion en Cancer de Mama (GEICAM).
This product can also be used for this purpose in clinical practice, Dr. Alba told Medscape Oncology in an interview. Currently, many women with metastatic breast cancer who respond to first-line therapy are not given any maintenance treatment, he said. Some clinicians offer hormone therapies, such as aromatase inhibitors or tamoxifen, and some offer targeted therapies, such as trastuzumab (Herceptin, Roche), if they are appropriate. But in many situations, clinicians offer nothing, he said. These results suggest that they could offer PLD as an option, as they did in this trial, he said.
Such a use is slightly outside the current indications for the product. PLD is approved in Europe for use as monotherapy in patients with metastatic breast cancer who are at increased cardiac risk, in a dose of 50?mg/m2 every 4 weeks.
In this trial, PLD was used as maintenance therapy for women who had responded to a first-line anthracycline/taxane combination, and it was used at a slightly lower dose of 40?mg/m2 once every 4 weeks for 6 cycles of therapy. The study protocol specified the dose reduction to manage hematologic reactions, the researchers explained.
The toxicity seen in this trial was "very low," Dr. Alba commented, adding that this was 1 of the main findings. This lower dose of PLD was not associated with any gastrointestinal toxicity, there was no grade?4 alopecia or grade?4 nausea and vomiting, and no cardiotoxicity (no increase in left ventricular ejection fraction or clinical congestive heart failure). Grade?3/4 hand-foot syndrome was seen in 4% of patients taking PLD, but other grade 3/4 toxicities were "unremarkable" and similar in both the treatment and observation groups, the researchers said.
Previous trials of chemotherapy for maintenance treatment in metastatic breast cancer have also shown longer time to progression, and sometimes longer overall survival, but the main drawback has been toxicity, Dr. Alba said. "In this setting, the treatment is not curative, but it is important to explore all the available alternatives," he said.
"Maintenance therapy is a good option for almost everybody, if we can design effective treatments associated with a good toxicity profile," he said. "I think this goal is achieved in the case of pegylated liposomal doxorubicin."
33rd European Society of Medical Oncology (ESMO) Congress: Abstract 145P. Presented September 15, 2008
[ 本帖最後由 goodcat1111 於 2008-9-30 14:51 編輯 ] |
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