Abraxane比紫杉醇更好的抗癌新药

    美国制药(American Pharmaceutical Partners,APP)和美国生物科学(American BioScience)近日宣布，美国FDA批准了Abraxane用于治疗转移性乳腺癌的新药申请。两家公司利用他们的专利纳米技术,把Abraxane的活性成分紫杉醇(Paclitaxel)和只有红细胞1%大小的纳米白蛋白颗粒结合在一起，从而避免了各种溶解可能。Abraxane是第一个非溶解纳米白蛋白结合化疗药物，可以有效的利用白蛋白受体内在途径传输药物通过肿瘤新生血管内皮细胞壁。与单纯紫杉醇相比，其作用时间更长，副作用小.

    下面是疗效的结果报道：
    · A significantly higher Overall Tumor Response Rate (ORR) was noted in patients receiving ABRAXANE&#8482; (33%) versus TAXOL&reg; (19%), (p=0.001). Similarly, analysis of the Target Lesion Response Rate (TLRR) showed significantly higher anti-tumor activity (p<0.001) with ABRAXANE&#8482;;

    · In patients receiving chemotherapy for metastatic breast cancer for the first time (first–line patients), a significantly higher tumor response was also noted, with 42% of ABRAXANE&#8482; patients (n=97) responding to the therapy compared with a 27% response rate in patients (n=89) receiving TAXOL (p=0.029);

    · Similarly, the response rates with ABRAXANE&#8482; were higher, and statistically significant, when analyzed in those patients who had failed prior chemotherapy, and in patients with poor prognostic indicators such as in those with liver metastases (26%, n=92 vs. 13%, n=97) and lung metastases (43%, n=74 vs. 25%, n=79);

    · A longer time to tumor progression was noted in patients receiving ABRAXANE&#8482;, with a median of 21.9 weeks versus a median progression time of 16.1 weeks after TAXOL, (p=0.030);

    · 98% of cycles of ABRAXANE&#8482; were administered without steroid premedication and no evidence of severe hypersensitivity reactions were noted in any of these patients thus confirming the ability to safely administer this solvent-free paclitaxel without the need for premedication. In contrast, 95% of the doses of TAXOL were administered with steroids and anti-histamines, and still these patients showed a significantly higher incidence of flushing than those patients receiving ABRAXANE without pre-medication;

    · Both treatments were well tolerated with 98% of patients receiving the planned dose on both arms; the mean total paclitaxel dose delivered with ABRAXANE&#8482; was 1459mg per patient per m2 and 909mg per patient per m2 with TAXOL;

    · Consistent with this higher dose of paclitaxel delivered with ABRAXANE&#8482;, the incidence of Grade 3 sensory neuropathy was 10% versus 2% in the patients receiving TAXOL (p<0.001). The Grade 3 sensory neuropathy resolved rapidly in the ABRAXANE&#8482; patients within a median of 22 days and was thus easily managed. In contrast, and consistent with current clinical experience, recovery of the neuropathy after TAXOL administration was significantly prolonged with a median of 79 days (p=0.028). This finding suggests that it is possible, consistent with preclinical studies in the literature, that the Cremophor component of TAXOL may be responsible for structural damage (demyelination) to the nerve fibres resulting in prolonged neuropathy, while neuropathy due to paclitaxel alone is transient with rapid resolution. There were no reports of Grade 4 sensory neuropathy or severe motor neuropathy in either arm;

    · Despite the higher dose of paclitaxel delivered, there was significantly less Grade 4 neutropenia with ABRAXANE&#8482; (9%) compared to TAXOL (22%), providing the first clinical evidence that Cremophor may contribute to bone marrow damage and loss of white blood cells;

    · Fluid retention was infrequent in both arms and there were no septic deaths in the study.

    "It is clear that the solvent Cremophor is not an innocent bystander," said William Gradishar, M.D., the Principal Investigator of the study. "The findings of this Phase III clinical trial provide the first clinical evidence that Cremophor may be responsible not only for the severe hypersensitvity reactions that necessitate steroid pre-medication, but that the toxic effects of this solvent on patients may be more far-reaching than previously recognized. Data from this trial suggest that Cremophor itself may be responsible for the loss of protective white blood cells, by suppressing the bone marrow, and, furthermore, that the solvent-induced damage to nerve fibres, rather than paclitaxel itself, may account for the prolonged recovery of peripheral neuropathy noted with TAXOL&reg;."

    "We are extremely pleased that the increase in anti-tumor activity we had seen with ABRAXANETM in preclinical studies was confirmed in this Phase III trial, and further translated into an increased time to tumor progression in patients with metastatic breast cancer," said Michael J. Hawkins, M.D., Chief Medical Officer at American BioScience, Inc., the company responsible for developing ABRAXANETM.

    "Our preclinical data indicated that higher intratumor concentrations of paclitaxel were achieved following administration of ABRAXANETM, compared to equal doses of TAXOL&reg;. This effect, coupled with our ability to increase the dose of paclitaxel administered, predicted that ABRAXANETM would have more anti-tumor activity than TAXOL. This is now supported by the results of our randomized Phase III study. We will now expeditiously complete filing of the NDA, which has been granted fast-track designation."

    有关这个药物的应用范围的评述（来自于FDA）：
    American Pharmaceutical Partners, Inc. (Nasdaq: APPX) and American BioScience, Inc. (ABI) today announced that the New Drug Application (NDA) for Abraxane has been accepted for filing with standard review by the U.S. Food and Drug Administration (FDA), indicating the FDA has determined that the application is sufficiently complete to permit a substantive review.

    The final portion of the NDA was submitted on March 8, 2004 under FDA''s Fast Track designation, as a treatment for metastatic breast cancer.

    "I am very proud of the tremendous effort by the entire development team in accomplishing this successful filing of an electronic NDA. FDA''s acceptance of this NDA filing moves us one step closer to providing a potential new treatment for metastatic breast cancer patients," said Patrick Soon-Shiong, M.D., Chairman, President and Chief Executive Officer of American Pharmaceutical Partners. "By meeting this important milestone our clinical development plan for Abraxane in breast cancer remains on track. With this acceptance we are now aggressively expanding our clinical development program to pursue indications in other malignancies such as non-small cell lung cancer and ovarian cancer, as well as combination therapies of Abraxane with other chemotherapeutic agents."

    The filing of the NDA is based primarily upon the pivotal randomized controlled Phase III trial that compared the safety and efficacy of 260 mg/m2 of Abraxane to 175 mg/m2 of Taxol administered every three weeks in 460 patients with metastatic breast cancer. The Phase III trial demonstrated that Abraxane resulted in an almost doubling of the response rate and a prolongation of time to tumor progression in first and second line patients with metastatic breast cancer.

    ABI and APP are strategic partners in the development, manufacture and marketing of Abraxane. ABI is responsible for the clinical development and registration of Abraxane. APP has licensed the exclusive North American manufacturing and marketing rights for Abraxane.

    About Breast Cancer
    According to the American Cancer Society (ACS), while early detection efforts have decreased mortality rates, in 2004 an estimated 215,990 women are expected to be diagnosed with breast cancer that had already spread. Breast cancer is still the leading overall cause of death in women between the ages of 20 and 59, with 40,110 deaths estimated in 2004. One of every three cancers diagnosed in the United States is breast cancer; excluding skin cancer, it''s the most common cancer among women.

    About the Companies
    American BioScience, Inc. is a privately held biotechnology company focused on the discovery, development and delivery of next-generation therapeutic moieties including biologically active molecules already existing within the human biological system, for the treatment of life-threatening diseases. American Pharmaceutical Partners, Inc. is a majority owned subsidiary of American BioScience, Inc.

    American Pharmaceutical Partners, Inc. is a specialty drug company that develops, manufactures and markets injectable pharmaceutical products, focusing on the oncology, anti-infective and critical care markets. APP has acquired the exclusive North American rights to manufacture and market Abraxane, a proprietary nanoparticle injectable oncology product that has completed Phase III clinical trials for metastatic breast cancer and for which the FDA has granted "Fast Track" designation. The NDA submission has commenced and the submission is now ongoing. The company believes that it has established the only commercial scale protein-engineered nanoparticle manufacturing capability in the United States.