PARP Inhibitors Cancer Review
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Novel Combinations of New and Existing Therapies Yield Promising Results for Leukemia Patients with Poor Prognoses

Novel Combinations of New and Existing Therapies Yield Promising Results for Leukemia Patients with Poor Prognoses | PARP Inhibitors Cancer Review | Scoop.it
Recognizing that leukemia cannot be conquered with a “one-size-fits-all” approach, researchers are pursuing novel targeted therapies and combinations of existing treatment regimens with new agents for patient populations with historically poor prognoses, according to data presented today during the 56th American Society of Hematology (ASH) Annual Meeting and Exposition.
Krishan Maggon 's insight:

In recent years, outcomes for patients with leukemia have steadily improved with the emergence of numerous therapies that target specific genetic drivers of disease, as well as potent combination regimens. While overall outcomes for patients with leukemia are improving as a result of these new therapies, some more vulnerable subgroups of patients, including elderly patients and patients with aggressive genetic mutations, have not experienced the same positive results.

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PARP Inhibitors Cancer Review
Poly ADP ribose polymerase (PARP) inhibitors for triple negative breast cancer (TNBC) The Phase III failure of Iniparib to extend OS or PFS in TNBC patients has cast a dark shadow on PARP inhibitors drug class and R&D in one of the most active area in industrial oncology. The most advanced product iniparib (BSI 201, Sanofi Aventis) has shown 30% response rates in Phase I trials and 62% in triple negative breast cancer patients in Phase II trials. Addition of Iniparib to chemotherapy increased overall survival to 12.2 months from 7.7 months on gemcitabine+ carboplatin. A global Phase III trial in squamous NSCLC was initiated in 2010. It has completed enrollment of TNBC patients in Phase III trials. The NDA and MAA is expected to be filed in 1-2 Q 2011. The second product olaparib has shown 40% response rates in extended Phase I trials and completed Phase II studies. Olaparib planned Phase III trials in BRCA1/BRCA2 positive breast cancer was cancelled by Astra Zeneca and focus shifted to Phase III in ovarian cancer patients. Olaparib extended PFS and time to progression by 4 and 4.6 months over placebo. Veliparib from Abbott is the third PARPi to complete Phase II trials in advanced metastatic breast cancer with 37% RR in BRCA positive patients. Tumor cells use PARP pathway to repair DNA damage to proliferate and replicate. A new test to identify defective genes RAD51 assay indicates that PARP inhibitors may benefit 60% of the ovarian cancer patients. Inhibition of PARP offers novel agents for treating tumors with DNA repair defects. PARP inhibitors have the market potential to generate 10-15 billion annual sales with each brand worth $3-5 billion in sales within 5 years after approval and marketing in major markets.
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FDA grants marketing approval to scalp cooling system for breast cancer chemotherapy patients. ecancer - News

FDA grants marketing approval to scalp cooling system for breast cancer chemotherapy patients. ecancer - News | PARP Inhibitors Cancer Review | Scoop.it
FDA grants marketing approval to scalp cooling system for breast cancer chemotherapy patients. ecancer - News https://t.co/6iSDMmaYfx https://t.co/dlytswcMD7
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Epigenetic modifiers: activities in renal cell carcinoma

Epigenetic modifiers: activities in renal cell carcinoma | PARP Inhibitors Cancer Review | Scoop.it
Our understanding of how mutations in chromatin modifiers contribute to tumorigenesis in RCC is improving but remains an area of intense investigation. Importantly, elucidating the activities of chromatin modifiers offers intriguing opportunities for the development of new therapeutic interventions in RCC.
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Genentech: Understanding Non-Hodgkin's Lymphoma

Genentech: Understanding Non-Hodgkin's Lymphoma | PARP Inhibitors Cancer Review | Scoop.it
Non-Hodgkin’s lymphoma, or NHL, is a disease in which malignant (cancerous) cells form in the lymph system, which is part of the immune system. It is one of the most common blood cancers among adults in the U.S.
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Genetic and transcriptional evolution alters cancer cell line drug response

Genetic and transcriptional evolution alters cancer cell line drug response | PARP Inhibitors Cancer Review | Scoop.it
The extent, origins and consequences of genetic variation within human cell lines are studied, providing a framework for researchers to measure such variation in efforts to support maximally reproducible cancer research.
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Proteasome inhibition induces IKK-dependent interleukin-8 expression in triple negative breast cancer cells: Opportunity for combination therapy

Proteasome inhibition induces IKK-dependent interleukin-8 expression in triple negative breast cancer cells: Opportunity for combination therapy | PARP Inhibitors Cancer Review | Scoop.it
Triple negative breast cancer (TNBC) cells express increased levels of the pro-inflammatory and pro-angiogenic chemokine interleukin-8 (IL-8, CXCL8), which promotes their proliferation and migration. Because TNBC patients are unresponsive to current targeted therapies, new therapeutic strategies...
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Treatment of Older Patients with Mantle-Cell Lymphoma | NEJM

Treatment of Older Patients with Mantle-Cell Lymphoma | NEJM | PARP Inhibitors Cancer Review | Scoop.it
Original Article from The New England Journal of Medicine — Treatment of Older Patients with Mantle-Cell Lymphoma...

 

R-CHOP induction followed by maintenance therapy with rituximab is effective for older patients with mantle-cell lymphoma. (Funded by the European Commission and others; ClinicalTrials.gov number, NCT00209209.)

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Spectral overlap-free quantum dot-based determination of benzo[a]pyrene-induced cancer stem cells by concurrent monitoring of CD44, CD24 and aldehyde dehydrogenase 1 - Chemical Communications (RSC ...

In this study, it was found that breast cancer stem cells (CSCs) are formed from MCF-7 cells by benzo[a]pyrene (BP)-induced mutation.The breast CSCs were detected through simultaneous monitoring of CD44, CD24 and aldehyde dehydrogenase 1 (ALDH1) by hypermulticolor cellular imaging using an acousto-optical...
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European Medicines Agency - Two new paediatric-use marketing authorisations recommended by CHMP

European Medicines Agency - Two new paediatric-use marketing authorisations recommended by CHMP | PARP Inhibitors Cancer Review | Scoop.it

The European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use(CHMP) has recommended granting two new paediatric-use marketing authorisations (PUMAs), for Kigabeq (vigabatrin) and Slenyto (melatonin).

PUMAs can be granted for authorised medicines which have been developed specifically for children and are no longer under patent protection. PUMAs aim to stimulate research of existing medicines for better treatments for children by giving the medicines ten years of market protection.

Slenyto is to be used for the treatment of insomnia in children from 2 years of age with autism spectrum disorder and Smith-Magenis syndrome (a disorder with a variety of features including intellectual disability, speech and language delay, distinctive facial features, difficulty sleeping and behavioural problems). Sleep disorders are common in children with developmental disabilities and are often difficult to treat. There are currently no approved medicines to treat insomnia in children. However, in practice doctors have been prescribing medicines off-label, including melatonin.

Slenyto has been developed specifically for children and is available in an age-appropriate form, in small tablets. A clinical trial provided scientific data on its efficacyand safety in this population. Its active substance, melatonin, is a naturally-occurring hormone which is normally produced by a gland in the brain called the pineal gland and is involved in coordinating the body’s sleep cycle. Data from the clinical trial and from the scientific literature suggest the medicine is associated with a significant increase in total sleep time, a shortened sleep latency (the time it takes to fall asleep after the lights have been turned out) and a longer duration of uninterrupted sleep. The main side effects observed in the clinical trial were somnolence (sleepiness), headache and fatigue.

Kigabeq, the other medicine recommended by the CHMP at this meeting, is meant for the treatment of infantile spasms (West's syndrome), an uncommon and severe form of epilepsy associated with a highly-resistant seizure type (epileptic spasms) and a rapid psychomotor regression, and in resistant partial epilepsy, in infants and children from 1 month to 7 years of age.

Vigabatrin, the active substance in Kigabeq, is an antiepileptic agent that was first authorised in European countries almost thirty years ago and is commonly used to treat adult and paediatric patients, in particular patients with forms of epilepsy which are difficult to manage. Currently vigabatrin is available in the European Union (EU) as 500 mg film-coated tablets or granules for oral solution sachets, which need to be split and/or diluted to make them appropriate for children.

Krishan Maggon 's insight:

The need for paediatric-specific formulations of vigabatrin and melatonin has been identified by EMA’s expert committee for medicines for children, the Paediatric Committee (PDCO), in its inventory of the needs for paediatric medicines, which aims to help medicine developers identify opportunities. The medicines were developed according to a paediatric investigation plan (PIP) agreed by the PDCO.

 

  • The applicant for Slenyto is RAD Neurim Pharmaceuticals EEC Ltd
  • The applicant for Kigabeq is Orphelia Pharma SAS
  • One medicine containing melatonin, Circadin, is centrally approved in the EU. It is used for the short-term treatment of primary insomnia (poor quality of sleep) in patients aged 55 years or over
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KDM8/JMJD5 as a dual coactivator of AR and PKM2 integrates AR/EZH2 network and tumor metabolism in CRPC

KDM8/JMJD5 as a dual coactivator of AR and PKM2 integrates AR/EZH2 network and tumor metabolism in CRPC | PARP Inhibitors Cancer Review | Scoop.it

together with its ability to activate EZH2, a factor known to be involved in castration and therapy resistance, make KDM8 a promising therapeutic target for PCa. Materials and methods Cell lines and cell culture RWPE1, LNCaP, PC3, C4-2B, DU145, CWR22V1, and HEK293 cells were obtained from the A

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Pancreatic cancer: treatment approaches and trends

Pancreatic cancer: treatment approaches and trends | PARP Inhibitors Cancer Review | Scoop.it
Journal of Cancer Metastasis and Treatment is an open access journal, focusing on basic and clinical studies related to cancer cell, cell biology, oncology, radiation therapy and radiology, obstetrics and gynecology, pediatrics, surgery, hematology, neuro-oncology, etc.
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A Small-molecule Kinase Inhibitor, CEP-1347, Inhibits Survivin Expression and Sensitizes Ovarian Cancer Stem Cells to Paclitaxel

A Small-molecule Kinase Inhibitor, CEP-1347, Inhibits Survivin Expression and Sensitizes Ovarian Cancer Stem Cells to Paclitaxel | PARP Inhibitors Cancer Review | Scoop.it
Abstract
Background: Chemoresistance of cancer stem cells (CSCs) is considered a major cause of post-treatment recurrence that negatively impacts the prognosis of patients with ovarian cancer. Materials and Methods: Using CSCs derived from two different ovarian cancer cell lines, we searched for molecules implicated in the chemoresistance of ovarian CSCs and also drugs with which to target those molecules. Results: Knockdown of survivin overexpressed in ovarian CSCs resulted in increased sensitivity to paclitaxel. Treatment at clinically relevant concentrations with CEP-1347, a mixed lineage kinase inhibitor with a known safety profile in humans, reduced survivin expression in ovarian CSCs and sensitized them to paclitaxel. Conclusion: Survivin overexpression plays a key role in the chemoresistance of ovarian CSCs. Introduction of CEP-1347, which targets survivin expression in ovarian CSCs, as a chemosensitizer for conventional ovarian cancer chemotherapy may serve as a rational and feasible approach for better management of ovarian cancer.
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EMA CHMP Recommends Granting a Marketing Authorisation for Lilly Abemaciclib | ESMO

EMA CHMP Recommends Granting a Marketing Authorisation for Lilly Abemaciclib | ESMO | PARP Inhibitors Cancer Review | Scoop.it
It is indicated for the treatment of HR-positive, HER2-negative locally advanced or metastatic breast cancer in combination with an aromatase inhibitor or fulvestrant..

 

On 26 July 2018, the European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation for the medicinal product abemaciclib (Verzenios), intended for the treatment of locally advanced or metastatic breast cancer. 

The applicant for this medicinal product is Eli Lilly Nederland B.V. 

Verzenios will be available as film-coated tablets (50 mg, 100 mg and 150 mg). The active substance of Verzenios is abemaciclib, a protein kinases inhibitor (ATC code: L01XE50) that potently and selectively inhibits cyclin-dependent kinases 4 and 6 (CDK4 and CDK6), leading to suppression of tumour growth. 

The benefit with Verzenios is its ability to significantly improve progression-free survival in combination with an aromatase inhibitor or fulvestrant

The most common side effects are diarrhoea, infections, neutropenia, anaemia, fatigue, nausea, vomiting and decreased appetite. 

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Progenics' FDA Approval Of Azedra Opens Up New Available Options For Cancer Patients With Rare Tumors - Progenics Pharmaceuticals Inc. (NASDAQ:PGNX)

Progenics' FDA Approval Of Azedra Opens Up New Available Options For Cancer Patients With Rare Tumors - Progenics Pharmaceuticals Inc. (NASDAQ:PGNX) | PARP Inhibitors Cancer Review | Scoop.it
Progenics Pharmaceuticals obtains FDA approval for Azedra.The FDA approval for Azedra was due to positive results from a  phase 2b study that had achieved both...
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PARP2 mediates branched poly ADP-ribosylation in response to DNA damage

PARP2 mediates branched poly ADP-ribosylation in response to DNA damage | PARP Inhibitors Cancer Review | Scoop.it
PARP1 and PARP2 of the PARP family enzymes are involved in DNA damage response. Here the authors report PARP2 activation mechanisms and its role in the formation of branched poly(ADP-ribose) chains in response to DNA damage.
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Dual role for miR-34a in the control of early progenitor proliferation and commitment in the mammary gland and in breast cancer

Dual role for miR-34a in the control of early progenitor proliferation and commitment in the mammary gland and in breast cancer | PARP Inhibitors Cancer Review | Scoop.it
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The effect of mesenchymal stem cells’ secretome on lung cancer progression is contingent on their origin: primary or metastatic niche

The effect of mesenchymal stem cells’ secretome on lung cancer progression is contingent on their origin: primary or metastatic niche | PARP Inhibitors Cancer Review | Scoop.it

Cell Sci. 2012;125(Pt 23):5591–6. 4. Quail DF, Joyce JA. Microenvironmental regulation of tumor progression and metastasis. Nat Med. 2013;19:1423–37. 5. Korkaya H, Wicha MS. Breast cancer stem cells: we’ve got them surrounded [...] Concise review: mesenchymal stem cell tumor-homing: detection methods

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TRIM44 promotes quiescent multiple myeloma cell occupancy and survival in the osteoblastic niche via HIF-1α stabilization

TRIM44 promotes quiescent multiple myeloma cell occupancy and survival in the osteoblastic niche via HIF-1α stabilization | PARP Inhibitors Cancer Review | Scoop.it

Given that most MM patients will undergo an autologous stem cell transplantation after standard therapies and eventually most patients relapse, understanding how quiescent cells hide in the OS niche to avoid therapies will have signi

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Targeting B-Cell Maturation Antigen (BCMA) Holds Promise for Multiple Myeloma Cure

Targeting B-Cell Maturation Antigen (BCMA) Holds Promise for Multiple Myeloma Cure | PARP Inhibitors Cancer Review | Scoop.it
Targeting B-Cell Maturation Antigen Holds Promise for Multiple Myeloma Cure.B Cells, TNFR, CAR-T, hematopoietic, bone marrow, BCMA, ADCs, Multiple myeloma...
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Mesothelial cells facilitate cancer stem‑like properties in spheroids of ovarian cancer cells

Mesothelial cells facilitate cancer stem‑like properties in spheroids of ovarian cancer cells | PARP Inhibitors Cancer Review | Scoop.it
Mesothelial cells facilitate cancer stem‑like properties in spheroids of ovarian cancer cells Authors: Akemi Shishido Seiji Mori Yuhki Yokoyama Yoshinosuke Hamada Kazumasa Minami Yamin Qian Jiaqi Wang Haruka Hirose Xin Wu Naomasa Kawaguchi Sachiko Nagumo Nariaki Matsuura Hirofumi Yamamoto View Affiliations Published online on: July 27, 2018     https://doi.org/10.3892/or.2018.6605 Metrics: HTML 0 views | PDF 0 views     Cited By (CrossRef): 0 citations Abstract Ovarian cancer is characterized by widespread peritoneal dissemination with ascites. Spheroids observed in the ascites of ovarian cancer patients are a mixture of cancer cells and mesothelial cells. In the present study, we evaluated whether mesothelial cells exfoliated from the peritoneum facilitate tumor spheroid formation and give rise to cancer stem‑like properties in ovarian cancer cells. Spheroids from the CAOV3 and A2780 ovarian cancer cell lines grew much larger in co‑culture with mesothelial cells than in monoculture under 3D conditions. The spheroids in co‑culture displayed high Ki‑67 expression in the peripheral zone and low expression in the central zone area. The expression of CD133 emerged in the inner portion of spheroids at later time‑points (96 and 168 h), indicating that cancer cells expanded to the inner spheroid and acquired stem cell‑properties. The mRNA levels of cancer stem cell markers Dclk‑1, CD44 and Bmi‑1 significantly increased in co‑cultured CAOV3 and mesothelial cells compared to CAOV3 cells alone. Furthermore, the mesothelial cells promoted the tumorigenesis and growth of the CAOV3 cells in a mouse xenograft model compared to cancer cells alone. In conclusion, mesothelial cells promoted spheroid formation by ovarian cancer cells and facilitated cancer stem‑like properties. Related Articles
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Cancer

Cancer | PARP Inhibitors Cancer Review | Scoop.it
DNA damage causes cancer. Causes of DNA mutations. Cancer spread metastasis. OBSTACLES THAT PREVENT US FROM CURING CANCER.Cancer Trademarks...
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Highly charged, cytotoxic, cyclometalated iridium(III) complexes as cancer stem cell mitochondriotropics - Laws - - Chemistry – A European Journal - Wiley Online Library

The cancer stem cell (CSC) toxicity and mechanism of action of a series of iridium(III) complexes bearing polypridyl and charged 1‐methyl‐2‐(2‐pyridyl)pyridinium ligands, 1‐4 is reported. The most effective complex (containing 1,10‐phenanthroline), 3 kills CSCs and bulk cancer cells with equal potency (in the micromolar range), indicating that it could potentially remove heterogenous tumour populations with a single dose. Encouraging, 3 also inhibits mammopshere formation to a similar extent as salinomycin, a well‐established anti‐CSC agent. This complex induces CSC apoptosis by mitochondrial membrane depolarization, inhibition of mitochondrial metabolism, and intracellular reactive oxygen species (ROS) generation. To the best of our knowledge, this is the first study to investigate the anti‐CSC properties of iridium complexes.
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Leukaemia hijacks a neural mechanism to invade the central nervous system

Leukaemia hijacks a neural mechanism to invade the central nervous system | PARP Inhibitors Cancer Review | Scoop.it
Here we show that ALL cells in the circulation are unable to breach the blood–brain barrier in mice; instead, they migrate into the CNS along vessels that pass directly between vertebral or calvarial bone marrow and the subarachnoid space. The basement membrane of these bridging vessels is enriched in laminin, which is known to coordinate pathfinding of neuronal progenitor cells in the CNS. The laminin receptor α6 integrin is expressed in most cases of ALL. We found that α6 integrin–laminin interactions mediated the migration of ALL cells towards the cerebrospinal fluid in vitro. Mice with ALL xenografts were treated with either a PI3Kδ inhibitor, which decreased α6 integrin expression on ALL cells, or specific α6 integrin-neutralizing antibodies and showed significant reductions in ALL transit along bridging vessels, blast counts in the cerebrospinal fluid and CNS disease symptoms despite minimally decreased bone marrow disease burden. Our data suggest that α6 integrin expression, which is common in ALL, allows cells to use neural migratory pathways to invade the CNS.
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Leukaemia follows a blood-vessel track to enter the nervous system

Leukaemia follows a blood-vessel track to enter the nervous system | PARP Inhibitors Cancer Review | Scoop.it
Certain cancers are prone to invade the nervous system, which leads to poorer prognosis. A study of leukaemia in mice reveals an unexpectedly direct invasion route from the bone marrow to the central nervous system.
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Reciprocal Regulation of DUSP9 and DUSP16 Expression by HIF1 Controls ERK and p38 MAP Kinase Activity and Mediates Chemotherapy-Induced Breast Cancer Stem Cell Enrichment

Reciprocal Regulation of DUSP9 and DUSP16 Expression by HIF1 Controls ERK and p38 MAP Kinase Activity and Mediates Chemotherapy-Induced Breast Cancer Stem Cell Enrichment | PARP Inhibitors Cancer Review | Scoop.it
Triple-negative breast cancer (TNBC) has a poor prognosis due to its aggressive characteristics and lack of targeted therapies. Cytotoxic chemotherapy may reduce tumor bulk, but leaves residual disease due to the persistence of chemotherapy-resistant breast cancer stem cells (BCSC), which are...
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European Medicines Agency ( EMA) restricts use of prostate cancer medicine Xofigo

European Medicines Agency ( EMA) restricts use of prostate cancer medicine Xofigo | PARP Inhibitors Cancer Review | Scoop.it

The European Medicines Agency (EMA) has concluded its review of the cancer medicine Xofigo (radium-223 dichloride), and has recommended restricting its use to patients who have had two previous treatments for metastatic prostate cancer (prostate cancer that has spread to the bone) or who cannot receive other treatments.

Xofigo must also not be used with the medicines Zytiga (abiraterone acetate) and the corticosteroid prednisone or prednisolone. Xofigo should not be used with other systemic cancer therapies, except for treatments to maintain reduced levels of male hormones (hormone therapy). The medicine should also not be used in patients who have no symptoms, in line with the current indication; in addition, the use of Xofigo is not recommended in patients with a low number of bone metastases called osteoblastic bone metastases.

The review of Xofigo was carried out by EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) after data from a clinical study suggested that patients given Xofigo in combination with Zytiga and prednisone/prednisolone could be at risk of dying earlier and had more fractures than patients given placebo (a dummy treatment) with Zytiga and prednisone/prednisolone. The study included patients with no or only mild symptoms, whereas Xofigo is only authorised in patients with symptoms. In addition, the combination used in this study is now contraindicated. In the study, patients given the combination with Xofigo died on average 2.6 months earlier than those given the combination with placebo. In addition, 29% of patients who received the Xofigo combination had fractures, compared with 11% of patients given the placebo combination.

It is thought that Xofigo, which is taken up by the bone, accumulates at sites where the bone is already damaged, for example by osteoporosis or micro-fractures, increasing the risk of fracture. However, the reasons for a possible earlier death seen in this study are not fully understood. The company that markets Xofigo will have to conduct studies to further characterise these events and clarify the mechanisms behind them.

The PRAC’s recommendations have now been endorsed by EMA’s Committee for Medicinal Products for Human Use (CHMP) and will be sent to the European Commission for a final legal decision.

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FDA Approves AZEDRA® (iobenguane I 131, Progenics Pharma ) to Treat Unresectable, Locally Advanced or Metastatic Pheochromocytoma or Paraganglioma

FDA Approves AZEDRA® (iobenguane I 131, Progenics Pharma ) to Treat Unresectable, Locally Advanced or Metastatic Pheochromocytoma or Paraganglioma | PARP Inhibitors Cancer Review | Scoop.it

 Progenics Pharmaceuticals, Inc.(Nasdaq:PGNX) today announced that the U.S. Food and Drug Administration (FDA) has approved the New Drug Application (NDA) for AZEDRA (iobenguane I 131) 555 MBq/mL injection for intravenous use. AZEDRA, a radiotherapeutic, is indicated for the treatment of adult and pediatric patients 12 years and older with iobenguane scan positive, unresectable, locally advanced or metastatic pheochromocytoma or paraganglioma who require systemic anticancer therapy.  AZEDRA is the first and only approved therapy for this indication.

 

AZEDRA can cause serious side effects including risk from radiation exposure, bone marrow problems and other cancers (myelosuppression and secondary malignancies), thyroid problems (hypothyroidism), elevations in blood pressure, kidney problems (renal toxicity), respiratory problems (pneumonitis), pregnancy warning (embryo-fetal toxicity), and fertility problems. Please see Important Safety Information below and Full Prescribing Information.

 

The FDA approval of AZEDRA was based on data from a pivotal phase 2 open-label, multi-center trial that was conducted under a Special Protocol Assessment (SPA) with the FDA. The final results showed that 17 of the 68 evaluable patients (25%) experienced a 50% or greater reduction of all antihypertensive medication for at least 6 months, achieving the primary endpoint specified in the SPA. The study also showed favorable results from a key secondary endpoint evaluating the proportion of patients with overall tumor response as measured by Response Evaluation Criteria In Solid Tumors (RECIST). Overall tumor response was achieved in 15 of the patients studied (22%). Of these 15 patients, 53% experienced durable tumor responses lasting 6 months or longer. The most common severe (Grade 3-4) adverse reactions were decrease in a specific type of white blood cell (lymphopenia, 78%), decrease in another type of white blood cell (neutropenia, 59%), decrease in platelets which are involved in blood clotting (thrombocytopenia, 50%), fatigue (26%), decrease in red blood cells (anemia, 24%), decrease in blood clotting time (increased international normalized ratio, 18%), nausea (16%), dizziness (13%), high blood pressure (hypertension, 11%), and vomiting (10%). Twelve percent of patients discontinued treatment due to adverse reactions.

Krishan Maggon 's insight:

AZEDRA (iobenguane I 131) is a later-stage drug candidate being developed for the treatment of malignant pheochromocytoma and paraganglioma.  Pheochromocytomas are rare tumors that arise from cells of the sympathetic nervous system.  Such tumors are usually found within one or both adrenal glands (85%), but may arise in other areas of sympathetic nerve cells, and are then referred to as paragangliomas.  We use a small molecule that specifically targets neuroendocrine tumors (such as pheochromocytoma and paraganglioma) and attach a radioisotope to create AZEDRA.  The patients are first imaged with this radiopharmaceutical to determine a therapeutic dose that is safe to normal organs and effective in destroying cancer cells. This imaging step is designed to enable the delivery of an individualized therapeutic dose that is optimized for each patient.

 

AZEDRA (iobenguane I 131) is a high specific activity form of iobenguane l 131, produced using our proprietary platform.  This technology is designed to prevent unlabeled or “cold” iobenguane from being carried through the manufacture process to the final formulation, and to produce a product of a high specific activity.  We are working to make AZEDRA deliver more effective tumor destructive power and avoid typical side effects from the use of a low specific activity product, and therefore to provide effective therapy for patients suffering from pheochromocytoma and paraganglioma.

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