Saturday, September 26, 2015

肺癌肋膜侵犯(Pleural spread)治療: 台大李章銘/陳克誠發表光動力 PHOTOFRIN(R) 毒殺成效

肺癌肋膜擴散非絕症 光動力毒殺癌細胞 2015/09/24 12:25 (中央社記者龍珮寧台北24日電)肺癌晚期肋膜擴散不是絕症,台大光動力治療,打入致敏劑給癌細胞吸收後,在雷射光刺激下現形,釋出大量自由基及過氧化合物,讓肉眼看不到的癌細胞被「毒」殺。台大醫院上午舉辦「惡性腫瘤的肋膜擴散不再是絕症,光動力治療在肺癌合作肋膜擴散的成果發表」,刊登在知名期刊「公共科學圖書館期刊(PLOS  ONE),也在今年世界肺癌大會發表,是全台灣最先使用光動力治療的醫院,目前還有部立桃園醫院。據國健署最新癌症發生登記數據顯示,101年共有11692人罹患肺癌,是發生人數第二名,不過卻是國人癌症死因第一位,國人常發生的是肺腺癌,透過篩檢可以早期診斷、早期治療。台灣大學校長楊泮池表示,有時候肺癌喜歡長在旁邊的地方,雖然不大但已侵犯到肋膜,而這是肺腺癌晚期治療效果不佳的原因,但是台大醫院團隊引進光動力治療,改善處理患者的困境,提高存活率。台大醫院外科部胸腔外科主任李章銘說,肺腺癌肺膜擴散的治療方式在過去是用手術切除,不過很難完全清除擴散在肋膜間的腫瘤細胞,治療上以化療或標靶治療為主,但治療情況不理想,也會復發,5年存活率10%以下。腫瘤醫學部醫師陳若白說,肋膜的位置是在肺的邊緣,在第四期中有4成患者是在靠近肋膜處,透過化療縮小腫瘤後再以手術切除,再透過光動力療法(POT)後,還要再搭配化療等療法。胸腔外科醫師陳克誠說,台大醫院5年前引進美國的光動力治療,讓本來不能手術的可以手術,肉眼可以看見腫瘤切除後,對於擴散且肉眼看不到的腫瘤,以光動刀方式找到癌細胞治療,目前已累計29名個案。李章銘說,在治療中或手術前注入「光致敏劑」,這會停留在癌細胞內,而不會出現在正常細胞,再以雷射光讓癌細胞現形後,會釋放大量自由基及過氧化合物「毒」殺癌細胞。李章銘說,以光動力治療的肺癌患者,近6年已有19例,其他癌症有10例,成果是肺癌患者3年存活率逾70%5年存活率有56%,未來將持續應用在不同癌症,手術是自費,且僅對惡性有肋膜擴散患者。

Pleural Photodynamic Therapy and Surgery in Lung Cancer and Thymoma Patients with Pleural Spread

Ke-Cheng Chen , Yi-Shan Hsieh , Ying-Fan Tseng, Ming-Jium Shieh, Jin-Shing Chen, Hong-Shiee Lai, Jang-Ming Lee  Published: July 20, 2015

Pleural spread is difficult to treat in malignancies, especially in lung cancer and thymoma. Monotherapy with surgery fails to have a better survival benefit than palliative chemotherapy, the currently accepted treatment. Photodynamic therapy utilizes a photosensitizer to target the tumor site, and the tumor is exposed to light after performing a pleurectomy and tumor resection. However, the benefits of this procedure to lung cancer or thymoma patients are unknown. We retrospectively reviewed the clinical characteristics and treatment outcomes of patients with lung cancer or thymoma with pleural seeding who underwent pleural photodynamic therapy and surgery between 2005 and 2013. Eighteen patients enrolled in this study. The mean patient age was 52.9 ± 12.2 years. Lung cancer was the inciting cancer of pleural dissemination in 10 patients (55.6%), and thymoma in 8 (44.4%). There was no procedure-related mortality. Using Kaplan-Meier survival analysis, the 3-year survival rate and the 5-year survival rate were 68.9% and 57.4%, respectively. We compared the PDT lung cancer patients with those receiving chemotherapy or target therapy (n = 51) and found that the PDT group had better survival than non-PDT patients (mean survival time: 39.0 versus 17.6 months; P = .047). With proper patient selection, radical surgical resection combined with intrapleural photodynamic therapy for pleural spread in patients with non-small cell lung cancer or thymoma is feasible and may provide a survival benefit. Pleural spread without distant metastases in thoracic malignancy is difficult to manage. In non-small cell lung cancer (NSCLC), it was stage IIIb in the previous International System for Staging Lung Cancer . The International Association for the Study of Lung Cancer (IASLC) published the seventh edition of the TNM classification of NSCLC in 2009 and changed the sixth edition of this document. The current IASLC lung cancer staging project committee recommended that pleural spreads, either malignant pleural effusions or pleural nodules, be upgraded from T4 to M1a. In patients with pleural carcinomatosis, the median survival time ranged from 6 to 9 months . Currently, the management options for pleural spread include chemotherapy, surgery with pleurectomy, and photodynamic therapy. Thymoma is neoplasm arising from epithelial thymic cells. Distant metastasis is rare but it more frequently shows pleural implantation upon diagnosis or after primary treatment. Thymoma with pleural spread is a difficult clinical situation to manage, and the treatment is controversial. … In our study, we used Porfimer sodium (Photofrin; Axcan Pharma Inc, Birmingham, AL, USA), a first-generation photosensitizer. 630 nm red light can activate the photosensitizer. Successful treatment of malignant mesothelioma by photodynamic therapy has been reported as a new approach for pleural malignancy dissemination . Moreover, like mesothelioma, PDT could be one of the multimodality treatment for NSCLC with pleural disseminations. A phase II trial for pleural spread, patients underwent surgery with complete resection or tumor debulking, followed by intrapleural PDT or PDT alone. The overall survival was significantly better than similar patients of historical controls .

PHOTOFRIN®, Pinnacle Biologics™ and the logo of Pinnacle Biologics™ are trademarks of


Pinnacle Biologics, Inc. See more. The PHOTOFRIN® trademark is owned by Concordia Laboratories Inc. PHOTOFRIN® is manufactured for Concordia Laboratories Inc. and distributed in the United States by Pinnacle Biologics Inc.

The role of PDT with PHOTOFRIN®1  PHOTOFRIN® is indicated for treatment of microinvasive endobronchial NSCLC in patients for whom surgery and radiotherapy are not indicated.Potential patient types include  Patients with microinvasive lung cancer, a tumor that invades beyond the basement membrane of the bronchial wall, but not into the cartilagePatients ineligible for surgery or radiotherapy due to: Prior high-dose radiotherapy /Poor pulmonary function/Multifocal multilobar disease/Poor medical condition Tumor response rate1,* In 3 noncomparative studies, PDT with PHOTOFRIN® was evaluated in 62 inoperable patients with microinvasive endobronchial tumors; 11 of them clearly documented as unsuitable for surgery or radiotherapy.

Source: http://www.photofrin.com/

 

About Concordia  Concordia is a diverse healthcare company focused on legacy pharmaceutical products and orphan drugs. Concordia's legacy pharmaceutical division, Concordia Pharmaceuticals Inc., consists of a portfolio of branded products and authorized generic contracts, including branded products such as Nilandron®, for the treatment of metastatic prostate cancer; Dibenzyline®, for the treatment of pheochromocytoma; Lanoxin®, for the treatment of mild-to-moderate heart failure and atrial fibrillation; Plaquenil®, for the treatment of lupus and rheumatoid arthritis, Donnatal® for the treatment of irritable bowel syndrome and Zonegran® (zonisamide) for treatment of partial seizures in adults with epilepsy. Concordia's orphan drugs division owns Photofrin®. Photofrin® is marketed by Pinnacle Biologics, Inc. in the United States. Concordia operates out of facilities in Oakville, Ontario; Bridgetown, Barbados; Roanoke, Virginia and has a specialty healthcare distribution (SHD) division that operates out of Kansas City, Missouri. Pinnacle Biologics, Inc. is located in Chicago, Illinois.

Forest Labs to Buy Aptalis for $2.9 Billion  Forest Seeks New Drugs to Replace Those Facing Generic Competition By MIKE SPECTOR And  JONATHAN D. ROCKOFF  Jan. 8, 2014 7:56 a.m. ETForest Laboratories Inc. agreed to buy specialty pharmaceutical company Aptalis Holdings Inc. for $2.9 billion in cash. Private-equity firm TPG purchased Aptalis, at the time called Axcan Pharma Inc., in 2008 for about $1.3 billion. Axcan later merged with Eurand NV to create a company that was renamed Aptalis. The Wall Street Journal had reported that Forest's board was meeting Tuesday night and was expected to approve the deal. Aptalis, which focuses on treatments for cystic fibrosis and gastrointestinal disorders, toward the end of December filed papers with regulators stating intentions to pursue an initial public offering. Private-equity-owned companies often run a so-called dual track process in which they prepare to take a company public while also soliciting an outright buyer. Aptalis has sales and marketing operations in the U.S., Canada, France and Germany and manufacturing operations in North America and Europe, according to regulatory filings. For the fiscal year ended Sept. 30, the company posted an $86.9 million profit, compared with a $12 million loss a year earlier. Sales rose 12% to $687.9 million. The deal, which requires antitrust review in the U.S. and Canada, is expected to add about 78 cents a share to Forest's adjusted earnings in 2015, along with nearly $700 million in revenue. The company also expects to see about $125 million in cost synergies as a result of the deal. Forest intends to use a combination of cash on hand and debt to fund the deal, which is expected to close in the first half. Forest, a midsize pharmaceutical company based in New York with a market capitalization exceeding $15 billion, develops, makes and sells a bevy of drugs, such as Linzess to treat irritable bowel syndrome. The company has been looking to find new drugs to replace blockbusters, such as the antidepressant Lexapro, that are facing competition from low-price generic versions. Some of the company's new drugs haven't met Wall Street expectations, and the Food and Drug Administration late last year delayed an approval decision on a schizophrenia treatment Forest is helping develop. Brent Saunders, the company's new chief executive, has outlined plans to cut $500 million in costs by 2016 while using Forest's cash to buy drugs it can fold into its portfolio. Mr. Saunders has said he wants to complement Linzess with other drugs treating gastrointestinal disorders with deals that boost earnings and cash flow. Aptalis provides such a fit. It sells gastrointestinal treatments such as ulcer therapy Carafate, and Canasa for a painful condition affecting the rectum called ulcerative proctitis.

Concordia Healthcare Announces Terms of US$520 Million Public Offering of Common Shares  Published: Sept 24, 2015 6:45 p.m. ET  TORONTO, Sept. 24, 2015 /PRNewswire/ - Concordia Healthcare Corp. ("Concordia" or the "Company") CXRX, -2.37% (CXR) today announced the size and pricing of its underwritten public offering (the "Offering") of 8,000,000 common shares of Concordia at a price of US$65.00 per common share (the "Offering Price"). The gross proceeds from the Offering are expected to be US$520 million. The Offering is being conducted by a syndicate of underwriters led by Goldman, Sachs & Co. and RBC Capital Markets, as lead book running managers, and Credit Suisse Securities (USA) LLC and Jefferies LLC, as additional book running managers (collectively and together with the Canadian affiliates of certain of the book running managers, the "Underwriters"). In addition, the Company has granted the Underwriters an option (the "Underwriters' Option") to purchase an additional 1,200,000 common shares of Concordia at the Offering Price per additional common share, exercisable at any time, and from time to time, in whole or in part, up to 30 days from the closing of the Offering. If the Underwriters' Option is exercised in full, the total gross proceeds to Concordia are expected to be US$598 million. The common shares will be sold pursuant to a final prospectus supplement (the "Supplement") to the short form base shelf prospectus dated July 16, 2015 to be filed with the securities regulatory authorities in each of the provinces of Canada and a final prospectus supplement (the "U.S. Supplement") to the corresponding registration statement on Form F-10 to be filed with the U.S. Securities and Exchange Commission. The net proceeds of the Offering will be used to fund, in part: (i) a portion of the purchase price for the previously announced acquisition by the Company of all of the outstanding shares in the capital of Amdipharm Mercury Limited (the "Acquisition"); and (ii) the fees and expenses incurred in connection with the Acquisition. In the event that the Acquisition is not completed, the net proceeds from the Offering will initially be added to the Company's working capital and will subsequently be used to fund future acquisitions in furtherance of the Company's business plan, for general corporate purposes and to potentially repay certain debt obligations of the Company. The Offering is expected to close on or about September 30, 2015 and is subject to the satisfaction of certain conditions including, but not limited to, the receipt of all necessary approvals, including the approval of the Toronto Stock Exchange. A copy of the Supplement and the U.S. Supplement may be obtained from the Company upon written request to Concordia at 277 Lakeshore Rd. East, Suite 302, Oakville, Ontario, L6J 1H9, telephone (905) 842-5150, Attn: Corporate Secretary. The Supplement also will be available on SEDAR at www.sedar.com and the U.S. Supplement also will be available on EDGAR at www.sec.gov. No securities regulatory authority has either approved or disapproved the contents of this press release. This press release does not constitute an offer to sell or a solicitation of an offer to buy any securities of the Company in any jurisdiction in which such offer, solicitation or sale would be unlawful.

     
patients undergoing PDT vs. non-PDT for pleural spread (P = 0.047)


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