Combidex - Ferumostan-10 geeft betrouwbare diagnostische resultaten (90 tot 100 procent) bij wel of niet uitzaaiingen bij prostaatkanker tot op 2 mm.doorsnede. FDA geeft goedkeuring

5 april 2012: De FDA had Combidex - ferumostran-10 goedgekeurd als aanvullende diagnose techniek voor prostaatkanker. Echter het Nederlandse bedrijf is gestopt en Combidex - Ferumostran is niet meer beschikbaar. Als u hier klikt kunt u een door de FDA semangesteld rapport lezen over waarom zij vonden dat Combidex - Ferumostran-10 waarde kan hebben. Het rapport is wel in het Engels en 86 bladzijden lang

d.d. 11 november 2003:

Een derde fase studie gepubliceerd in New England Journal of medicin bevestigd uiterst betrouwbare diagnostiek van wel of niet uitzaaiingen bij prostaatkanker tot op 2 mm. doorsnede. Aan deze studie deed ook de Radboud Nijmegen mee. .

Study in New England Journal of Medicine Shows Advanced Magnetics’ Combidex® Enables
Early Diagnosis of Lymph Node Metastases in Prostate Cancer Patients

Combidex Able to Detect Lymph Node Metastases as Small as 2 Millimeters

Cambridge, MA, and Princeton, NJ (June 18, 2003) -- Advanced Magnetics, Inc. (Amex: AVM) and Cytogen Corporation (Nasdaq: CYTO) today announced the publication of clinical data in this week’s New England Journal of Medicine showing that magnetic resonance (MR) imaging with Combidex®, an investigational iron oxide nanoparticle, aids in the non-invasive evaluation of lymph nodes in patients with prostate cancer. Researchers, led by Mukesh Harisinghani, MD, assistant radiologist at Massachusetts General Hospital (MGH) and Jelle Barentsz, MD, Professor of Radiology at the University Medical Center Nijmegen (UMCN) in the Netherlands, concluded that the use of Combidex-enhanced MR imaging allows for the detection of small and otherwise undetectable lymph node metastases in patients with prostate cancer.

In an accompanying perspective “New Horizons in Oncologic Imaging” by Koh, et. al., the authors stated “[these imaging techniques] represent major advances in cancer imaging, which may help optimize patient care by pinpointing even the smallest tumors and providing a functional assessment of malignant disease.”

“This study provides further evidence of the important role Combidex can play in the diagnosis and treatment of cancer patients as a critical tool to differentiate between metastatic and normal lymph nodes. We believe that Combidex can significantly contribute to helping physicians more accurately identify the spread of cancer to lymph nodes,” stated Jerome Goldstein, Chairman and Chief Executive Officer of Advanced Magnetics. “The ability to identify metastatic nodes through the use of Combidex-enhanced MR imaging that might otherwise be overlooked by current imaging guidelines is a significant step forward for the oncology community.”

The study published by Dr. Harisinghani involved 40 patients from MGH and 40 patients from UMCN with prostate cancer, who were scheduled either for surgical lymph node resection or nodal biopsy. The researchers performed MR imaging before and 24 hours after the administration of Combidex. In one of the evaluations done, the researchers determined whether or not each patient had any metastatic nodes. For these evaluations on a patient-by-patient basis, when the before and after MR scans were compared to pathology, the use of Combidex-enhanced MR imaging improved accuracy from 65% to 98% and improved the positive predictive value from 60% to 94%. Sensitivity, the probability that the diagnosis is positive given the presence of disease, increased from 45% to 100%. Specificity, the likelihood that given the absence of disease the diagnosis is negative, increased from 79% to 96%. Of the 33 patients in whom metastatic disease was found, the researchers noted that 9 of those patients had metastatic lymph nodes outside of the standard area for surgical exploration that would not have been found by current standard diagnostic procedures.

“This study demonstrates the potential role of Combidex for changing the way cancer is currently diagnosed and treated, not only in prostate cancer patients but also across the disease category,” commented Michael Becker, President and Chief Executive Officer of Cytogen Corporation, which has exclusive U.S. marketing rights to Combidex. “Current treatment guidelines provide for imaging studies to determine the extent and spread of disease, including to lymph nodes, for the prognosis and treatment of many cancers. However, the assessment of lymph node status is currently based on the size of the node. This important new study further demonstrates that Combidex could fill an unmet medical need for more accurate ways of differentiating between malignant and non-malignant lymph nodes. We look forward to bringing Combidex to market and to offering this non-invasive tool to physicians throughout the United States.”

Additionally, the researchers analyzed the results based on the diagnosis of each individual node. Results of the node-by-node diagnoses with Combidex resulted in accuracy of 97%, sensitivity of 91%, specificity of 98% and a positive predictive value of 95%. Of the nodes that were determined malignant by pathology, 71% were 10 mm or less in size and therefore did not fulfill the traditional imaging criteria for malignancy. Nodal evaluation using Combidex-enhanced images for nodes between 5 mm and 10 mm in size resulted in accuracy of 99%, sensitivity of 96%, specificity of 99% and an increase in the positive predictive value compared to unenhanced MR images from 29% to 96%. Dr. Harisinghani and his colleagues also noted that they were able to detect metastatic disease as small as 2 mm in size which is below the threshold of detection of any other imaging technique.

For some of the patients in this study, Dr. Harisinghani and his team at MGH also used the images to develop three-dimensional reconstructions of patient anatomy that were helpful in identifying both normal and malignant nodes in relationship to important surgical landmarks such as vessels and nerves. Utilization of this technique could prove to be an important tool for physicians performing surgery on these patients.

Computed tomography (CT) and MR imaging are the methods currently used for imaging lymph nodes. Current guidelines for imaging lymph nodes are that nodes greater than 10 mm in size are usually deemed cancerous while nodes less than 10 mm in size are generally presumed normal. Without a lymph-node specific contrast agent, CT and MR imaging cannot distinguish between lymph nodes that are enlarged due to the infiltration of cancerous cells as opposed to inflammation nor can these methods reliably detect disease in nodes that are not enlarged. Previous published findings in patients with breast, head and neck, urologic, and pelvic cancers have confirmed the potential for improved detection of lymph node metastases by using Combidex-enhanced imaging when compared to unenhanced or gadolinium-enhanced MR imaging.

Combidex, the lead product in Advanced Magnetics’ development pipeline, received an approvable letter, subject to certain conditions, from the U.S. Food and Drug Administration (FDA) for use in the diagnosis of lymph node disease. Advanced Magnetics continues to work with the FDA to resolve the outstanding issues from the approvable letter in an effort to bring Combidex to the market.