作者：Zosia Chustecka
出處：WebMD醫學新聞
December 12, 2008(聖安東尼奧) — 新資料顯示zoledronic acid (Zometa，Novartis藥廠)對乳癌有直接效果。這個雙磷酸鹽類藥物目前用於骨質疏鬆和骨骼轉移，但是有越來越多證據顯示它對乳癌也有療效。
於聖安東尼奧乳癌研討會第31屆年會中發表的臨床試驗次組初步結果顯示，當zoledronic acid與化療一起用於新的輔助治療時，和單用化療者相比，併用者可以獲得原發腫瘤顯著縮小的效果。
此外，此間發表的分子研究資料顯示，併用可以獲得基因表現數量的改變、以及與細胞週期調節和細胞凋亡的蛋白質改變，但是單獨使用時不會有這些改變。英國Sheffield大學腫瘤醫學教授Robert Coleman醫師表示，Zoledronic acid本身沒有明顯的效果，但是與化療併用時，可獲得相當不錯的協同效果。
這些新結果是今年第二次指出zoledronic acid對於乳癌有效的研究。當併用化療時，它顯著減少了「Austrian Breast and Colorectal Cancer Study Group trial 12」試驗中的早期乳癌復發比率。這些結果發表於今年的美國臨床腫瘤學會會議中，Medscape Oncology 當時也有報導。
【新輔助增加了腫瘤的縮小】
AZURE (Neo-Adjuvant Zoledronic Acid to Reduce Recurrence)試驗的最新資料，包括了3,360名第2或3期乳癌病患，病患接受標準的新輔助化療，於術前合併或未合併使用zoledronic acid，之後於術後以標準輔助化療合併或未合併使用zoledronic acid。該研究由藥廠贊助。
本試驗的整體結果仍在評估中，但是在這次年會中，Coleman醫師發表了其中205名病患進行回溯病理分析的初步結果。
這些病患的結果顯示，加入zoledronic acid可以獲得腫瘤縮小更多的結果。術後，平均殘餘腫瘤大小在接受化療與zoledronic acid (20.5)者小於單用化療者(30.0 mm)(P= .002)。此外，併用組有10.8%的婦女有完整病理反應，單用化療組則為5.8% (P= .02)。
【較少婦女進行乳房切除】
共同作者、Sheffield大學臨床研究員Matthew Winter醫師解釋表示，在這個新輔助設定中，目標是減少腫瘤大小，以潛在改善乳房保留比率以及長期結果；在此次分析中，併用組較少女性需要乳房切除術(65.3%)，單用化療組則為77.9%。
Winter醫師在聲明中表示，結果支持併用化療與zoledronic acid對於乳癌的新輔助治療有潛在的抗腫瘤好處。
Coleman醫師強調，這些結果來自回溯與實驗分析，因此，它們需被視為產生假設；但是如果AZURE試驗的整體結果證實這些發現，它們可以造成實務上的改變。
根據Novartis藥廠發言人表示，AZURE的最後結果預期在2或3年內發表，並且提到Novartis致力於將zoledronic acid 作為抗癌治療。
【較少骨質流失】
會中的另一場發表指出zoledronic acid對於另一組乳癌病患的效果；ZO-FAST (Zometa-Femara Adjuvant Synergy Trial)試驗評估zoledronic acid 對於有早期乳癌之停經婦女併用芳香族酶抑制劑letrozole時的骨骼流失治療效果。36個月時評估骨質密度的期中結果顯示，雙磷酸鹽可有效預防骨骼流失，由主要研究者、德國Frauenklinik大學的Holger Eidtmann醫師發表。
不過，他指出，該結果也顯示對乳癌的效果。在這個研究中，一組病患在整個研究期間都服用zoledronic acid(直接zoledronic-acid組)，另一組只有在骨質密度下降或者發生骨折時服用該藥(延遲zoledronic-acid組)；他報告指出，直接組比延遲組顯著降低疾病復發率(22 例相較於37例; P= .0423)。
當被問及是否會建議使用zoledronic acid於復發風險增加的乳癌病患時，Eidtmann醫師表示不會，他認為目前為時尚早；這些結果只有3年追蹤資料。但是相信zoledronic acid對於乳癌有抗腫瘤作用。
AZURE 和ZO-FAST都是由Novartis贊助。Coleman醫師報告接受Novartis的發言人費用。Eidtmann醫師宣稱沒有相關資金上的往來。
聖安東尼奧乳癌研討會第31屆年會：摘要2151, 5101與44。發表於2008年12月12-13日。
SABCS 2008: Zoledronic Acid Has Direct Effect on Breast Cancer
By Zosia Chustecka
Medscape Medical News
December 12, 2008 (San Antonio, Texas) — New data suggest that zoledronic acid (Zometa, Novartis) has a direct effect on breast cancer. The bisphosphonate is currently marketed for osteoporosis and bone metastasis, but there is growing evidence to suggest that it might also have a role to play in breast cancer.
Preliminary results from a clinical-trial subset presented here at the 31st Annual San Antonio Breast Cancer Symposium show that when zoledronic acid was used with chemotherapy in the neoadjuvant setting, the combination led to a significantly greater shrinkage of the primary tumor than was seen with chemotherapy alone.
Together with chemotherapy, you get this exquisite synergy.
Also, data from molecular studies presented here show that the combination produces a change in the expression of a number of genes and proteins associated with cell-cycle regulation and apoptosis, but neither produced these changes when used alone. "Zoledronic acid on its own had no appreciable effect, but together with chemotherapy, you get this exquisite synergy," commented coauthor Robert Coleman, MD, FRCP, professor of medical oncology at the University of Sheffield, United Kingdom.
These new results are the second time this year that zoledronic acid has shown an effect on breast cancer. When added to adjuvant chemotherapy, it significantly reduced the relapse rate in early breast cancer in the Austrian Breast and Colorectal Cancer Study Group trial?12. These results were presented at this year's American Society of Clinical Oncology meeting, and reported by Medscape Oncology at that time.
Neoadjuvant Use Increased Tumor Shrinkage
The latest data come from the AZURE (Neo-Adjuvant Zoledronic Acid to Reduce Recurrence) trial, conducted in 3360 patients with stage?2 or 3 breast cancer. Patients received standard neoadjuvant chemotherapy with or without the addition of zoledronic acid before surgery, and then standard adjuvant chemotherapy with or without zoledronic acid after surgery. The study was funded by the manufacturer.
The overall results of this trial are still being evaluated, but at the San Antonio meeting, Dr. Coleman presented preliminary results for a subgroup of 205 patients for whom a retrospective pathology analysis had been performed.
The results from this subgroup suggest that the addition of zoledronic acid leads to a greater shrinkage of the primary tumor. After surgery, the median residual tumor size was significantly smaller in women receiving both chemotherapy and zoledronic acid (20.5?mm vs 30.0?mm) than in those receiving chemotherapy alone (P?= .002). In addition, a complete pathologic response was seen in 10.8% of women in the combination group vs 5.8% of those in the chemotherapy-alone group (P?= .02).
Fewer Women Had a Mastectomy
In this neoadjuvant setting, the goal is to reduce the size of the tumor, and in doing so to potentially improve breast conservation rates and longer-term outcomes, explained coauthor Matthew Winter, MBChB, MSc, clinical research fellow at the University of Sheffield. In this analysis, fewer women in the combination group required a mastectomy (65.3% compared with 77.9% in the chemotherapy-alone group).
"The results support a potential antitumor benefit of combining zoledronic acid with chemotherapy in the neoadjuvant treatment of breast cancer," Dr. Winter commented in a statement.
Dr. Coleman emphasized that these results come from a retrospective and exploratory analysis and, hence, they should be regarded as hypothesis generating. But if the results from the overall AZURE trial confirm these findings, they could be practice changing, he suggested.
The final results from AZURE are expected in the next 2 or 3 years, according to a Novartis spokesperson, who said Novartis is "committed to further exploring zoledronic acid as an anticancer treatment."
Less Bone Loss
Another presentation at the meeting reported an effect of zoledronic acid on breast cancer in yet another setting. ZO-FAST (Zometa-Femara Adjuvant Synergy Trial) assessed the effect of zoledronic acid on bone loss associated with the aromatase inhibitor letrozole in postmenopausal women with early breast cancer. The interim results at 36 months, assessed by bone-mineral-density measurements, show that the bisphosphonate is effective in preventing this bone loss, reported lead researcher Holger Eidtmann, MD, from University Frauenklinik, in Kiel, Germany.
However, the results also show an effect on breast cancer, he noted. In this study, one group of patients took zoledronic acid throughout the study (the immediate-zoledronic-acid group), and the other group took the drug only if bone-mineral density fell or they had a fracture (the delayed-zoledronic-acid group). The immediate group had a significantly lower disease recurrence than the delayed group (22 events vs 37 events; P?= .0423), he reported.
When asked whether he would recommend zoledronic acid for breast cancer patients who are at increased risk for relapse, Dr. Eidtmann said: "No, I think it is too early for that; these results are only 3-year follow-up [data]. But I do believe that there is antitumor activity of zoledronic acid in breast cancer."
AZURE and ZO-FAST were funded by Novartis. Dr. Coleman reported serving on the speakers' bureau for Novartis. Dr. Eidtmann has disclosed no relevant financial relationships.
31st Annual San Antonio Breast Cancer Symposium (SABCS): Abstracts 2151, 5101, and 44. Presented December 12 and 13, 2008.
[ 本帖最後由 goodcat1111 於 2008-12-23 10:40 編輯 ] |
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