国际乳腺癌研讨会公布轰动性研究结果

医学空间

　　2003年12月6日，国际乳腺癌研讨会在美国圣安东尼奥闭幕，国际著名的乳腺癌研究组（BCIRG）在会上公布了一项轰动性的研究结果：一种以泰索帝（多西紫杉醇）为基础的化疗方案（泰索帝/阿霉素/环磷酰胺-TAC方案）作为早期乳腺癌术后辅助化疗产生了较常规标准化疗方案明显更佳的5年生存结果，该方案使乳腺癌患者死亡风险降低30%，癌症复发率降低28%。

　　该实验由最具权威的国际乳腺癌研究组（BCIRG）负责启动，这一多中心试验从1997年6月至1999年6月两年当中，共有20个国家，112个临床试验点，1，491名早期乳腺癌患者入组试验（绝经前和绝经后的妇女均包括在内）。实验结果有力证实：在长达55个月的随访期内，以泰索帝为基础的化疗方案（TAC）较目前常规的早期乳腺癌术后化疗标准方案（FAC）显著提高患者5年生存率，降低30%的死亡风险率和28%的癌症复发风险率，为全球早期乳腺癌患者带来生存的新希望。

　　目前全球每年约有120万妇女患乳腺癌，30多万人因此死去。在中国的一些主要城市，乳腺癌发病率的快速上升正引起医学界和公众的强烈关注。对于每年新确诊的30万早期乳腺癌患者如果接受TAC方案辅助治疗，在5年时就可多挽救18，000名患者的生命，这具有极其重要的社会意义。

　　国际乳腺癌研究组学术委员会成员Mackey博士在会上指出：“近5年的随访数据令人激动！对于肿瘤医生来说，疗效评估上有2～3%的改善，就给了我们足够的理由改变用药方案，而这次实验结果表明新方案对于生存的改善远远超过了上述的标准”

　　泰索帝的研制厂家安万特公司是国际领先的制药企业之一，而此次的实验结果也是医学界在早期乳腺癌术后化疗领域的重要突破。我国著名肿瘤学专家孙燕院士曾在中期结果发表时就表示，“以泰索帝为基础的（TAC）化疗方案同样适用于我国乳腺癌患者，并对国内临床肿瘤医师具有重要的指导意义。期待临床上的推广应用，令更多乳腺癌患者从中获益”。

　　Latest SABCS Newsletter Issues for 2003

　　ISSUE 1： December 3， 2003

　　ISSUE 2： December 4， 2003

　　ISSUE 3： December 5， 2003

　　Taxotere Study Shows Improved Survival and Reduced Relapse in Early-Stage Breast Cancer

　　Second interim analysis to support U.S. and EU registrational submissions for adjuvant breast cancer

　　Aventis Press Release

　　Strasbourg， France – An updated analysis of an important study shows the Aventis chemotherapy agent Taxotere (docetaxel) significantly improved the survival rate of women with early-stage breast cancer and reduced their risk of a relapse compared with a standard treatment.

　　The Breast Cancer International Research Group (BCIRG) 001/ TAX 316 study， presented at the San Antonio Breast Cancer Symposium on December 5， showed women with node-positive， early-stage breast cancer who received a Taxotere-based chemotherapy regimen after surgery experienced a 30 percent reduction in the risk of death at a 55-month follow-up and a 28 percent reduction in the chance of their cancer returning as compared to women treated with a commonly used， standard (post-surgery) adjuvant regimen.

　　The first analysis of BCIRG001 presented at American Society of Clinical Oncology (ASCO) in May 2002 by Dr. Jean Marc Nabholtz， who designed the trial， showed that the Taxotere combination arm had strong activity in both women with hormone-receptor positive or hormone-receptor negative tumors. The current analysis shows Taxotere to be the only taxane that demonstrates a disease-free survival benefit for women， regardless of hormone-receptor status of their tumors.

　　Aventis plans to use the phase III study data to support submissions for U.S. and EU approval in early 2004 for the use of Taxotere in treating early-stage operable breast cancer with involved axillary lymph nodes. Taxotere is currently indicated as a therapy for treatment of locally advanced or metastatic breast cancer after prior failure of chemotherapy.

　　“These mature data， which reflects nearly five years of follow-up， are exciting as they demonstrate that adding Taxotere to a standard anthracycline regimen in the adjuvant setting can significantly reduce the risk of relapse for women with early-stage breast cancer，” said John Mackey， MD， a member of the BCIRG Scientific Committee and Chair of the Northern Alberta Breast Cancer Program at the Cross Cancer Institute in Edmonton， Canada. “The results of this study suggest that we may be able to cure more women with early-stage disease by providing them a highly effective adjuvant chemotherapy regimen。”

　　Study Results and Protocol

　　The study compared the combination of Taxotere， doxorubicin (Adriamycin) and cyclophosphamide (Cytoxan)， (TAC)， with the standard regimen of 5-fluorouracil， doxorubicin and cyclophosphamide， (FAC). The 55-month follow-up results from this study were presented as a late-breaking oral presentation at the San Antonio symposium.

　　The multi-center study， conducted by BCIRG， enrolled 1，491 pre- and post-menopausal women with early-stage breast cancer from 112 sites in 20 countries between June 1997 and June 1999. Women were randomized to receive either TAC or FAC in the adjuvant (post-surgery) setting.

　　Among the findings of the study was a 28 percent improvement in the primary endpoint of disease-free survival (p=0.0010) for patients treated with TAC; as compared to FAC. A similar benefit was observed regardless of nodal， hormone-receptor and HER-2/neu status. The study results showed a 30 percent reduction in the risk of death (p=0.0080) for women treated with the Taxotere-based regimen.

　　“The outcomes from this important trial demonstrate that Taxotere extends the lives of woman with node positive disease，” said Dr. Frank Douglas， Executive Vice President for Drug Innovation & Approval and a Member of the Management Board of Aventis. “We are encouraged by these results in early stage breast cancer， and we will be using this data to support our submissions for regulatory approval early next year for Taxotere in this setting. ”

　　Adverse events manageable

　　Long-term follow-up of women on the study did not identify any new safety concerns beyond those already presented at the time of the first interim analysis.

　　Specifically， the TAC regimen was associated with a higher rate of febrile neutropenia (low white blood cell count that can lead to infections) compared with FAC (24.7 percent versus 2.5 percent). However， this increase in febrile neutropenia did not lead to an increased incidence of severe infection， and there were no toxic deaths from infection. Also， patients in the study were not treated prophylactically with GCSF (granulocyte colony-stimulating factor)， an effective and widely used agent to prevent neutropenia in chemotherapy patients.

　　The study compared an equal number of treatment cycles for both treatment groups and more than 90 percent of patients in both treatment groups received all six cycles of treatment.

　　Breast Cancer

　　Breast cancer is the most common cancer among women other than skin cancer. It is the second-leading cause of cancer death in women after lung cancer —— and is the leading cause of cancer death among women ages 40 to 591. More than 1，000，000 new cases of breast cancer are reported worldwide annually and more than 300，000 women die each year from the disease2. The risk of a woman developing breast cancer during her lifetime is approximately 11 percent (about one in nine of all women)， with about three to four percent dying of the disease1.

　　Aventis Commitment to Oncology

　　Taxotere， the foundation of Aventis oncology franchise， is currently indicated to treat non-small cell lung cancer and metastatic breast cancer. In 2002， the drug generated worldwide sales of ？ 1.3 billion. The Breast Cancer International Research Group trial is one of multiple trials worldwide to study Taxotere’s safety and efficacy in early stage breast， cancer， prostate， head and neck， and gastric cancers.

　　In addition to Taxotere， Aventis markets Campto (irinotecan)， a reference treatment for advanced colorectal cancer， and Anzemet (dolasetron mesylate)， an inhibitor for the treatment of chemotherapy induced nausea and vomiting.

　　Aventis also has a rich pipeline of investigational oncology compounds， including AVE-8062， a unique antivascular agent; flavopiridol， a novel cell cycle inhibitor; novel taxoids， that may offer benefits over available taxanes; and the ALVAC cancer vaccines being developed through the vaccines business of Aventis.

　　In 2002， Aventis entered a global agreement with Genta Inc. to jointly develop and commercialize Genasense within the US. Aventis has been granted sole marketing rights outside the US. Genasense is a pro-apoptotic that directly inhibits the production of Bcl-2， a protein made by cancer cells that is thought to block chemotherapy-induced cell death. The results from the Phase 3 clinical study of Genasense plus chemotherapy in patients with malignant melanoma were announced in September. In conjunction with these results， the first portion of the New Drug Application (NDA) has been submitted to the Food and Drug Administration (FDA) for Genasense in this indication.

　　In July 2003， Aventis and ImmunoGen signed a collaboration agreement to discover， develop， and commercialize novel antibody-based anti-cancer products.

　　In September 2003， Aventis and Regeneron Pharmaceuticals entered into a global (excluding Japan) agreement under which the companies will jointly develop and commercialize Vascular Endothelial Growth Factor (VEGF) Trap， Regeneron’s lead anti-angiogenesis compound.

　　About Aventis

　　Aventis is dedicated to treating and preventing disease by discovering and developing innovative prescription drugs and human vaccines. In 2002， Aventis generated sales of ？ 17.6 billion， invested ？ 3.1 billion in research and development and employed approximately 71，000 people in its core business. Aventis corporate headquarters are in Strasbourg， France. For more information， please visit： www.aventis.com

　　Statements in this news release containing projections or estimates of revenues， income， earnings per share， capital expenditures， capital structure， or other financial items; plans and objectives relating to future operations， products， or services; future economic performance; or assumptions underlying or relating to any such statements， are forward-looking statements subject to risks and uncertainties. Actual results could differ materially depending on factors such as the timing and effects of regulatory actions， the results of clinical trials， the company’s relative success developing and gaining market acceptance for new products， the outcome of significant litigation， and the effectiveness of patent protection. Additional information regarding risks and uncertainties is set forth in the current Annual Report on Form 20-F of Aventis on file with the Securities and Exchange Commission and in the current Annual Report -Document de Reference- on file with the Commission des Operations de Bourse in France， recently renamed “Autorite des marches financiers”.

　　References：

　　1- National Alliance of Breast Cancer Organizations

　　2- World Health Organization——GLOBOCAN database (2000 estimates)

2004.02.02