Iron Chelation and Kidney Cancer
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From: ironjustice on 2 Jul 2008 08:40 Senetek PLC (SNTK) Results Published in the Journal Cancer Demonstrate that Oral Talactoferrin Alfa is Active as Monotherapy in Previously Treated Patients with Metastatic Renal Cell Carcinoma 7/1/2008 http://tinyurl.com/56sr6q HOUSTON, July 1 /PRNewswire/ -- Agennix Incorporated today announced the publication of final results from a Phase 2 monotherapy trial with talactoferrin alfa in patients who had failed previous treatment for advanced or metastatic renal cell carcinoma (RCC). Results from the study, which were reported in the July 1 issue of the journal 'Cancer' (volume 113, number 1), demonstrate that talactoferrin is active in RCC, has a favorable toxicity profile, and is a promising candidate for further study in this disease. The talactoferrin monotherapy single arm trial was conducted at six leading U.S. centers and enrolled 44 patients who had all failed prior treatment for advanced or metastatic RCC. The study met the pre- defined target of demonstrating an improvement in the fourteen week progression-free survival (PFS) rate relative to published results in this population. Additional evidence of anti-cancer activity included the occurrence of partial responses and an apparent increase in median PFS and median overall survival (OS) relative to published results. As in previous studies with talactoferrin, the drug was well tolerated. "The results seen with talactoferrin monotherapy in this Phase 2 trial are promising," said Dr. Eric Jonasch, Assistant Professor, MD Anderson Cancer Center, Houston, Texas, and the first author of the study. "The trial results indicate that additional studies of talactoferrin in patients with RCC are warranted either as a single agent or in combination with one of the newer targeted therapies. Previously conducted preclinical studies combining talactoferrin with sunitinib are supportive for examining this combination in a randomized trial in patients with advanced or metastatic RCC." Agennix also announced the receipt of Orphan Medicinal Product designation from the European Medicines Agency (EMEA) for RCC. The Company had previously announced receipt of Orphan Drug designation from the U.S. Food and Drug Administration (FDA) for the same indication. Final Phase 2 Study Results The Phase 2 talactoferrin monotherapy trial was an open label, 44- patient, single arm trial conducted at six leading U.S. sites. To be eligible, patients with histologically confirmed metastatic or unresectable RCC had to have disease progression after being treated with at least one prior regimen of systemic therapy. Computed tomography (CT) scan documentation of disease progression following the most recent therapy was required. Talactoferrin was administered at a dose of 1.5 grams twice a day in 14-week cycles (12 weeks on, two weeks off) for up to four cycles or until disease progression. The study's co-primary endpoints were to detect an increase in the 14-week progression-free survival (PFS) rate from 20% to 40% or a 12.5% response rate, either of which were considered to be clinically significant. In a Phase 2 trial of Avastin in second line RCC patients, the placebo arm had a 4-month PFS rate of 20%, and was chosen as the historical reference. All 44 patients were included in the intent-to-treat (ITT) population. The study met the pre-defined target with a 14-week PFS rate of 59% (p<0.0001 for comparison to 20%). The response rate was 4.5%, with 70.5% of patients demonstrating stable disease for at least 8 weeks. The disease control (complete or partial response + stable disease) rate was 75%. The median PFS was 6.4 months. The median overall survival (OS) was 21.1 months, and the 1 year survival rate was 77%. Talactoferrin was well tolerated with no significant hematological, renal or hepatic toxicities reported. In addition, there were no drug related serious adverse events. About EMEA Orphan Medicinal Product Designation The Regulation on Orphan Medicinal Products in the European Union (EU) provides incentives for companies developing and marketing therapies for rare diseases, defined as those affecting fewer than five in 10,000 people in the EU. The Regulation grants companies with Orphan Medicinal Product designation market exclusivity for a particular indication for a period of ten years following Marketing Authorization Approval by the EMEA. Orphan Medicinal Product designation also facilitates the drug development process by providing companies with protocol assistance, clinical trial support, direct access to the Centralized Procedure, grant funding for research, and waiver or reduction of application fees. The Company had previously received Orphan Drug designation for RCC from the U.S. FDA. "We are very pleased that the EMEA recognizes that our lead product, talactoferrin alfa, has potential as a treatment for patients with RCC, and we are planning additional trials in this indication including a randomized, placebo-controlled Phase 2b trial of talactoferrin in combination with a standard first-line therapy," said Rajesh Malik, M.D., Chief Medical Officer of Agennix. About the Planned Phase 2b First-Line Combination Therapy RCC Trial Building on the results of the positive Phase 2 trial with single agent talactoferrin, preparations are underway to conduct a Phase 2b trial in 200-250 previously untreated patients with advanced or metastatic RCC as part of a first-line combination therapy regimen. Patients will be randomly assigned to receive a standard therapy plus either oral talactoferrin or placebo. The primary endpoint will be assessment of PFS, with additional endpoints including response rate, OS, and safety. About Talactoferrin Alfa Talactoferrin, a novel dendritic cell recruiter and activator (DCRA), is a unique recombinant form of human lactoferrin, an important immunomodulatory protein. In 1988, scientists at Baylor College of Medicine, Houston, Texas, discovered a way to produce this protein in the laboratory, thus paving the way for testing its potential to help fight serious diseases that cause enormous suffering worldwide. Lactoferrin, found in the highest concentration in milk, is expressed throughout the body in immune cells and on all body surfaces exposed to the external environment. Lactoferrin plays an important role in helping to establish the immune system, including the Gut Associated Lymphoid Tissue (GALT), in infants. Talactoferrin is produced in Aspergillus niger, a filamentous fungus, and is structurally identical to native human lactoferrin in all material respects, differing only in its glycosylation. Talactoferrin is an orally administered protein that mediates its activity through the gut and the GALT -- the largest lymphoid organ in the body. It acts through a novel mechanism of dendritic cell recruitment and activation. Following oral administration, talactoferrin is transported by the M-cells into the small intestinal Peyer's Patches, where it recruits circulating immature dendritic cells bearing tumor antigens to the GALT and induces their maturation. DC maturation in the presence of tumor antigens and lymphoid effector cells induces a strong systemic innate and adaptive immune response mediated by anti-cancer Natural Killer (NK) cells, CD8+ lymphocytes and NK-T cells. This results in the activation of tumor-draining lymph nodes, cellular infiltration of distant tumors and tumor-cell death. Mounting the initial immune response in the GALT -- away from the primary tumor and using a physiologically important pathway -- minimizes the effect of the cancer's local immunosuppressive defenses. About Renal Cell Carcinoma (RCC) RCC is the most common type of kidney cancer, accounting for approximately 90 percent of kidney tumors. In the United States, RCC affects over 40,000 patients per year, and is responsible for close to 13,000 deaths. Kidney cancer is uncommon under age 45, and its incidence is highest between the ages of 55 and 84. Once RCC is metastatic, it is difficult to treat, and median survival is between one and two years. A number of different modalities are available for the treatment of metastatic RCC, including immunotherapy, chemotherapy, targeted therapy, and/or radiation therapy. Some of the targeted therapies include multi-targeted tyrosine kinase inhibitors such as sunitinib (Sutent) and sorafenib (Nexavar), inhibitors of the mammalian target of rapamycin, such as temsirolimus (Torisel), and the anti-vascular endothelial growth factor (VEGF) antibody, bevacizumab (Avastin). Although each agent can provide some benefit in a subset of patients, complete response is exceedingly rare, and most patients with metastatic RCC die of their disease. Additional therapy is clearly needed. About Agennix Agennix is a private biotechnology company developing a first-in-class molecule with activity in several types of cancer and in other indications with unmet medical needs. This molecule, talactoferrin, is a targeted dendritic cell recruiter and activator with a novel mechanism of action. Agennix is preparing to initiate Phase 3 trials in two NSCLC indications (talactoferrin in combination with chemotherapy in previously untreated patients and talactoferrin monotherapy in patients who have failed two or more previous therapies), a Phase 2b trial in renal cell cancer, and Phase 2 trials in other indications. Talactoferrin's potential advantages in NSCLC and in other tumor types include its promising anti-tumor activity, its well tolerated safety profile including a reduction of some chemotherapy toxicities, its oral route of administration, and its apparent usefulness in multiple tumor types both as a single agent and in combination with other drugs. Agennix retains all of the commercial and economic rights to talactoferrin for all indications worldwide, and has strong global intellectual property protection for talactoferrin. More information about Agennix is available on the Company's web site at http://www.agennix.com. CONTACT: Rick Barsky, Chief Executive Officer, +1-713-552-1091, or Atul Varadhachary, President & COO, +1-713-552-1091, both of Agennix, Inc.; or Marissa Nelson, Media, of BMC Communications Group for Agennix, Inc., +1-212-477-9007, ext. 21 Web site: http://www.agennix.com/ Who loves ya. Tom Jesus Was A Vegetarian! http://tinyurl.com/2r2nkh Man Is A Herbivore! http://tinyurl.com/4rq595 DEAD PEOPLE WALKING http://tinyurl.com/zk9fk
From: ironjustice on 4 Jul 2008 10:51 On Jul 2, 5:40 am, ironjustice <teamtan...(a)hotmail.com> wrote:talactoferrin << Sooo .. you think a person should have a high iron meal WHEN one takes this very expensive iron binding .. drug .. ? "Iron-binding" Phase I trial of oral talactoferrin alfa in refractory solid tumors Authors: Hayes, Teresa1; Falchook, Gerald; Varadhachary, Gauri; Smith, Dori; Davis, Lisa; Dhingra, Hari; Hayes, Benjamin; Varadhachary, Atul Source: Investigational New Drugs, Volume 24, Number 3, May 2006 , pp. 233-240Abstract: Background: Lactoferrin is an iron-binding glycoprotein first identified in breast milk as a protein product of mammary epithelial cells. Its immunomodulatory functions include activation of NK and lymphokine- activated killer cells and enhancement of PMN and macrophage cytotoxicity. Studies in animal models have shown promising anti-cancer activity. The purpose of the present study was to evaluate the safety and tolerability of talactoferrin alfa (talactoferrin; TLF) in humans, as well as pharmacokinetics and pharmacodynamics. Methods: Ten adult patients with progressive advanced solid tumors who had failed conventional chemotherapy were administered oral TLF at doses from 1.5 to 9 g/day, using a 2 weeks on, 2 weeks off schedule. Patients were evaluated for drug toxicity, tumor growth rate, talactoferrin pharmacokinetics and cytokine markers. Results: Talactoferrin was very well tolerated. No hematological, hepatic, or renal toxicities were reported. A single patient had Grade 2 diarrhea, and there were no Grade 3 or 4 toxicities. Following oral administration, significant levels of talactoferrin were undetectable in circulation, but a statistically significant increase in circulating IL-18, a pharmacodynamic indicator of talactoferrin activity, was observed. Of the eight patients who were radiologically evaluable, five (63%) had stable disease by RECIST criteria two months after start of therapy, including one patient with a minor response. Seven patients (88%) had a decrease in their tumor growth rate. The three patients with non-small cell lung cancer (NSCLC) all survived for at least one year following the start of talactoferrin monotherapy. Conclusions: Talactoferrin is a promising, well-tolerated new agent that should be evaluated further in patients with refractory metastatic cancer. Keywords: talactoferrin; nonsmall cell lung cancer; refractory cancer Document Type: Research article DOI: 10.1007/s10637-005-3690-6 Affiliations: 1: Email: thayes(a)bcm.tmc.edu Who loves ya. Tom Jesus Was A Vegetarian! http://tinyurl.com/2r2nkh Man Is A Herbivore! http://tinyurl.com/4rq595 DEAD PEOPLE WALKING http://tinyurl.com/zk9fk > Senetek PLC (SNTK) Results Published in the Journal Cancer Demonstrate > that OralTalactoferrinAlfa is Active as Monotherapy in Previously > Treated Patients with Metastatic Renal Cell Carcinoma > 7/1/2008 > > http://tinyurl.com/56sr6q > > HOUSTON, July 1 /PRNewswire/ -- Agennix Incorporated today announced > the publication of final results from a Phase 2 monotherapy trial withtalactoferrinalfa in patients who had failed previous treatment for > advanced or metastatic renal cell carcinoma (RCC). Results from the > study, which were reported in the July 1 issue of the journal > 'Cancer' (volume 113, number 1), demonstrate thattalactoferrinis > active in RCC, has a favorable toxicity profile, and is a promising > candidate for further study in this disease. > > Thetalactoferrinmonotherapy single arm trial was conducted at six > leading U.S. centers and enrolled 44 patients who had all failed prior > treatment for advanced or metastatic RCC. The study met the pre- > defined target of demonstrating an improvement in the fourteen week > progression-free survival (PFS) rate relative to published results in > this population. Additional evidence of anti-cancer activity included > the occurrence of partial responses and an apparent increase in median > PFS and median overall survival (OS) relative to published results. As > in previous studies withtalactoferrin, the drug was well tolerated. > > "The results seen withtalactoferrinmonotherapy in this Phase 2 trial > are promising," said Dr. Eric Jonasch, Assistant Professor, MD > Anderson Cancer Center, Houston, Texas, and the first author of the > study. "The trial results indicate that additional studies oftalactoferrinin patients with RCC are warranted either as a single > agent or in combination with one of the newer targeted therapies. > Previously conducted preclinical studies combiningtalactoferrinwith > sunitinib are supportive for examining this combination in a > randomized trial in patients with advanced or metastatic RCC." > > Agennix also announced the receipt of Orphan Medicinal Product > designation from the European Medicines Agency (EMEA) for RCC. The > Company had previously announced receipt of Orphan Drug designation > from the U.S. Food and Drug Administration (FDA) for the same > indication. > > Final Phase 2 Study Results > > The Phase 2talactoferrinmonotherapy trial was an open label, 44- > patient, single arm trial conducted at six leading U.S. sites. To be > eligible, patients with histologically confirmed metastatic or > unresectable RCC had to have disease progression after being treated > with at least one prior regimen of systemic therapy. Computed > tomography (CT) scan documentation of disease progression following > the most recent therapy was required.Talactoferrinwas administered > at a dose of 1.5 grams twice a day in 14-week cycles (12 weeks on, two > weeks off) for up to four cycles or until disease progression. The > study's co-primary endpoints were to detect an increase in the 14-week > progression-free survival (PFS) rate from 20% to 40% or a 12.5% > response rate, either of which were considered to be clinically > significant. In a Phase 2 trial of Avastin in second line RCC > patients, the placebo arm had a 4-month PFS rate of 20%, and was > chosen as the historical reference. > > All 44 patients were included in the intent-to-treat (ITT) population. > The study met the pre-defined target with a 14-week PFS rate of 59% > (p<0.0001 for comparison to 20%). The response rate was 4.5%, with > 70.5% of patients demonstrating stable disease for at least 8 weeks. > The disease control (complete or partial response + stable disease) > rate was 75%. The median PFS was 6.4 months. The median overall > survival (OS) was 21.1 months, and the 1 year survival rate was 77%.Talactoferrinwas well tolerated with no significant hematological, > renal or hepatic toxicities reported. In addition, there were no drug > related serious adverse events. > > About EMEA Orphan Medicinal Product Designation > > The Regulation on Orphan Medicinal Products in the European Union (EU) > provides incentives for companies developing and marketing therapies > for rare diseases, defined as those affecting fewer than five in > 10,000 people in the EU. The Regulation grants companies with Orphan > Medicinal Product designation market exclusivity for a particular > indication for a period of ten years following Marketing Authorization > Approval by the EMEA. Orphan Medicinal Product designation also > facilitates the drug development process by providing companies with > protocol assistance, clinical trial support, direct access to the > Centralized Procedure, grant funding for research, and waiver or > reduction of application fees. > > The Company had previously received Orphan Drug designation for RCC > from the U.S. FDA. > > "We are very pleased that the EMEA recognizes that our lead product,talactoferrinalfa, has potential as a treatment for patients with > RCC, and we are planning additional trials in this indication > including a randomized, placebo-controlled Phase 2b trial oftalactoferrinin combination with a standard first-line therapy," said > Rajesh Malik, M.D., Chief Medical Officer of Agennix. > > About the Planned Phase 2b First-Line Combination Therapy RCC Trial > > Building on the results of the positive Phase 2 trial with single > agenttalactoferrin, preparations are underway to conduct a Phase 2b > trial in 200-250 previously untreated patients with advanced or > metastatic RCC as part of a first-line combination therapy regimen. > Patients will be randomly assigned to receive a standard therapy plus > either oraltalactoferrinor placebo. The primary endpoint will be > assessment of PFS, with additional endpoints including response rate, > OS, and safety. > > AboutTalactoferrinAlfa > > Talactoferrin, a novel dendritic cell recruiter and activator (DCRA), > is a unique recombinant form of human lactoferrin, an important > immunomodulatory protein. > > In 1988, scientists at Baylor College of Medicine, Houston, Texas, > discovered a way to produce this protein in the laboratory, thus > paving the way for testing its potential to help fight serious > diseases that cause enormous suffering worldwide. > > Lactoferrin, found in the highest concentration in milk, is expressed > throughout the body in immune cells and on all body surfaces exposed > to the external environment. Lactoferrin plays an important role in > helping to establish the immune system, including the Gut Associated > Lymphoid Tissue (GALT), in infants.Talactoferrinis produced in > Aspergillus niger, a filamentous fungus, and is structurally identical > to native human lactoferrin in all material respects, differing only > in its glycosylation. > > Talactoferrinis an orally administered protein that mediates its > activity through the gut and the GALT -- the largest lymphoid organ in > the body. It acts through a novel mechanism of dendritic cell > recruitment and activation. Following oral administration,talactoferrinis transported by the M-cells into the small intestinal > Peyer's Patches, where it recruits circulating immature dendritic > cells bearing tumor antigens to the GALT and induces their maturation. > DC maturation in the presence of tumor antigens and lymphoid effector > cells induces a strong systemic innate and adaptive immune response > mediated by anti-cancer Natural Killer (NK) cells, CD8+ lymphocytes > and NK-T cells. This results in the activation of tumor-draining lymph > nodes, cellular infiltration of distant tumors and tumor-cell death. > Mounting the initial immune response in the GALT -- away from the > primary tumor and using a physiologically important pathway -- > minimizes the effect of the cancer's local immunosuppressive defenses. > > About Renal Cell Carcinoma (RCC) RCC is the most common type of kidney > cancer, accounting for approximately 90 percent of kidney tumors. In > the United States, RCC affects over 40,000 patients per year, and is > responsible for close to 13,000 deaths. Kidney cancer is uncommon > under age 45, and its incidence is highest between the ages of 55 and > 84. > > Once RCC is metastatic, it is difficult to treat, and median survival > is between one and two years. A number of different modalities are > available for the treatment of metastatic RCC, including > immunotherapy, chemotherapy, targeted therapy, and/or radiation > therapy. Some of the targeted therapies include multi-targeted > tyrosine kinase inhibitors such as sunitinib (Sutent) and sorafenib > (Nexavar), inhibitors of the mammalian target of rapamycin, such as > temsirolimus (Torisel), and the anti-vascular endothelial growth > factor (VEGF) antibody, bevacizumab (Avastin). Although each agent can > provide some benefit in a subset of patients, complete response is > exceedingly rare, and most patients with metastatic RCC die of their > disease. Additional therapy is clearly needed. > > About Agennix > > Agennix is a private biotechnology company developing a first-in-class > molecule with activity in several types of cancer and in other > indications with unmet medical needs. This molecule,talactoferrin, is > a targeted dendritic cell recruiter and activator with a novel > mechanism of action. Agennix is preparing to initiate Phase 3 trials > in two NSCLC indications (talactoferrinin combination with > chemotherapy in previously untreated patients andtalactoferrin > monotherapy in patients who have failed two or more previous > therapies), a Phase 2b trial in renal cell cancer, and Phase 2 trials > in other indications.Talactoferrin'spotential advantages in NSCLC > and in other tumor types include its promising anti-tumor activity, > its well tolerated safety profile including a reduction of some > chemotherapy toxicities, its oral route of administration, and its > apparent usefulness in multiple tumor types both as a single agent and > in combination with other drugs. Agennix retains all of the commercial > and economic rights totalactoferrinfor all indications worldwide, > and has strong global intellectual property protection fortalactoferrin. > > More information about Agennix is available on the Company's web site > athttp://www.agennix.com. > > CONTACT: Rick Barsky, Chief Executive Officer, +1-713-552-1091, or > Atul > Varadhachary, President & COO, +1-713-552-1091, both of Agennix, Inc.; > or > Marissa Nelson, Media, of BMC Communications Group for Agennix, Inc., > +1-212-477-9007, ext. 21 > > Web site:http://www.agennix.com/ > > Who loves ya. > Tom > > Jesus Was A Vegetarian!http://tinyurl.com/2r2nkh > > Man Is A Herbivore!http://tinyurl.com/4rq595 > > DEAD PEOPLE WALKINGhttp://tinyurl.com/zk9fk
From: ironjustice on 4 Jul 2008 11:05 On Jul 4, 7:51 am, ironjustice <teamtan...(a)hotmail.com> wrote:"Iron- binding" << Novel nutriceutical pharmaceutical formulation. They microencapsulate the antioxidants INTO microdroplets of oil. Sounds like a salad. Antioxidants are antioxidation which is oxidation which is .. rust. ---------------------- Latest Weapon in Fighting Cancer A novel technique for reducing tumors in rats-using nano-sized, oil- based emulsions may be the latest weapon in fighting cancer. The technique, part of the burgeoning field of nutraceuticals, involves creating nanoemulsions, or nano-sized capsules made from oil and water. The emulsions, which are so small they are measured in nanometersor 1/100 of a meterare then filled with various antioxidants or anti-cancer fighting compounds, and tests show they can reduce tumors in rats. Researchers at the University of Massachusetts Lowell injected rats with neuroblastoma, so they would develop tumors, and then treated them with nanoemulsions containing antioxidants. They found that while the rats fed in the control group continued to develop tumors, the growth rate for those fed antioxidants was actually negative 65 percent, meaning the tumors actually shrank. They had about 70 percent total tumor regression, said Professor Robert Nicolosi, director of UMass Lowells Center for Health and Disease Research. When researchers exposed melanoma cancer cells to a nanoemulsion containing curcumin, an anti-cancer compound found in turmeric, cancer cell proliferation was greatly reduced, Nicolosi said. And when they used a nanoemulsion containing tamoxifen, a drug used to fight breast cancer, they just about eliminated the ability of the cells to proliferateat least in a cell culture, Nicolosi said. Nanoemulsion delivery systems have been shown to increase the bioavailablity and efficacy of certain drugs. The advantage, particularly for some of the toxic compounds used in fighting cancer, is that less of that compound is needed to achieve the same effect. That means the patient would suffer fewer damaging side effects. Theres no question were reducing the toxicity when we use 10 to 20 times less, Nicolosi said. Umass has been using Microfluidizer materials processing equipment to develop the nutraceutical products. The equipment has helped standardize the size of the nanoemulsions, making them more commercially viable. Prior to the Microfluidizer, nanoemulsions came out in varying sizes, making them less effective and less likely to gain approval by the US Food and Drug Administration, according to Scott McMeil, director of the Nanotechnology Characterization Laboratory at SAIC-Frederick, Inc. Nanoemulsions have been around for several years, but they werent very stable. But with a Microfluidizer, it looks like its overcoming the stability issue, McNeil said. McNeil, whose company is subcontracted by the National Cancer Institute, said the FDA requires that a compound is stable before it will grant its seal of approval. Before researchers began using the Microfluidizer, the size of the various nanoemulsions might vary from five nanometers to five microns, in one solution, making the solution less stable. A company would not move forward with something that was that high risk, McNeil said. The Microfluidizer has opened up new opportunities, such as nanoemulsions. In order to create the nanoemulsion, scientists mix water, an emulsifier like lecithin, and an antioxidant or anti-cancer fighting compound, and then pour it into a Microfluidizer processor. The processor then compresses the solution and drives it through tiny microchannels, and then in a reaction chamber, it splits the solution into two streams, which collide with each other at extremely high speeds. The collision creates a nanoemulsion that has a long shelf life. Researchers, such as UMass are also using the Microfluidizer processors to create foods, beverages, and nutritional supplements that can reduce inflammation or inhibit the intestines ability to absorb cholesterol, thus reducing blood cholesterol levels as well as the risk of heart disease. Posted July 1st, 2008 Who loves ya. Tom Jesus Was A Vegetarian! http://tinyurl.com/2r2nkh Man Is A Herbivore! http://tinyurl.com/4rq595 DEAD PEOPLE WALKING http://tinyurl.com/zk9fk > On Jul 2, 5:40 am, ironjustice <teamtan...(a)hotmail.com> > wrote:talactoferrin << > > Sooo .. you think a person should have a high iron meal WHEN one takes > this very expensive iron binding .. drug .. ? > > "Iron-binding" > > Phase I trial of oral talactoferrin alfa in refractory solid tumors > Authors: Hayes, Teresa1; Falchook, Gerald; Varadhachary, Gauri; Smith, > Dori; Davis, Lisa; Dhingra, Hari; Hayes, Benjamin; Varadhachary, Atul > > Source: Investigational New Drugs, Volume 24, Number 3, May 2006 , pp. > 233-240Abstract: > > Background: > Lactoferrin is an iron-binding glycoprotein first identified in breast > milk as a protein product of mammary epithelial cells. > Its immunomodulatory functions include activation of NK and lymphokine- > activated killer cells and enhancement of PMN and macrophage > cytotoxicity. > Studies in animal models have shown promising anti-cancer activity. > The purpose of the present study was to evaluate the safety and > tolerability of talactoferrin alfa (talactoferrin; TLF) in humans, as > well as pharmacokinetics and pharmacodynamics. > Methods: > Ten adult patients with progressive advanced solid tumors who had > failed conventional chemotherapy were administered oral TLF at doses > from 1.5 to 9 g/day, using a 2 weeks on, 2 weeks off schedule. > Patients were evaluated for drug toxicity, tumor growth rate, > talactoferrin pharmacokinetics and cytokine markers. > Results: > Talactoferrin was very well tolerated. No hematological, hepatic, or > renal toxicities were reported. > A single patient had Grade 2 diarrhea, and there were no Grade 3 or 4 > toxicities. Following oral administration, significant levels of > talactoferrin were undetectable in circulation, but a statistically > significant increase in circulating IL-18, a pharmacodynamic indicator > of talactoferrin activity, was observed. > Of the eight patients who were radiologically evaluable, five (63%) > had stable disease by RECIST criteria two months after start of > therapy, including one patient with a minor response. > Seven patients (88%) had a decrease in their tumor growth rate. > The three patients with non-small cell lung cancer (NSCLC) all > survived for at least one year following the start of talactoferrin > monotherapy. > Conclusions: > Talactoferrin is a promising, well-tolerated new agent that should be > evaluated further in patients with refractory metastatic cancer. > Keywords: talactoferrin; nonsmall cell lung cancer; refractory cancer > > Document Type: Research article > > DOI: 10.1007/s10637-005-3690-6 > > Affiliations: 1: Email: tha...(a)bcm.tmc.edu > > Who loves ya. > Tom > > Jesus Was A Vegetarian!http://tinyurl.com/2r2nkh > > Man Is A Herbivore!http://tinyurl.com/4rq595 > > DEAD PEOPLE WALKINGhttp://tinyurl.com/zk9fk > > > > > Senetek PLC (SNTK) Results Published in the Journal Cancer Demonstrate > > that OralTalactoferrinAlfa is Active as Monotherapy in Previously > > Treated Patients with Metastatic Renal Cell Carcinoma > > 7/1/2008 > > >http://tinyurl.com/56sr6q > > > HOUSTON, July 1 /PRNewswire/ -- Agennix Incorporated today announced > > the publication of final results from a Phase 2 monotherapy trial withtalactoferrinalfa in patients who had failed previous treatment for > > advanced or metastatic renal cell carcinoma (RCC). Results from the > > study, which were reported in the July 1 issue of the journal > > 'Cancer' (volume 113, number 1), demonstrate thattalactoferrinis > > active in RCC, has a favorable toxicity profile, and is a promising > > candidate for further study in this disease. > > > Thetalactoferrinmonotherapy single arm trial was conducted at six > > leading U.S. centers and enrolled 44 patients who had all failed prior > > treatment for advanced or metastatic RCC. The study met the pre- > > defined target of demonstrating an improvement in the fourteen week > > progression-free survival (PFS) rate relative to published results in > > this population. Additional evidence of anti-cancer activity included > > the occurrence of partial responses and an apparent increase in median > > PFS and median overall survival (OS) relative to published results. As > > in previous studies withtalactoferrin, the drug was well tolerated. > > > "The results seen withtalactoferrinmonotherapy in this Phase 2 trial > > are promising," said Dr. Eric Jonasch, Assistant Professor, MD > > Anderson Cancer Center, Houston, Texas, and the first author of the > > study. "The trial results indicate that additional studies oftalactoferrinin patients with RCC are warranted either as a single > > agent or in combination with one of the newer targeted therapies. > > Previously conducted preclinical studies combiningtalactoferrinwith > > sunitinib are supportive for examining this combination in a > > randomized trial in patients with advanced or metastatic RCC." > > > Agennix also announced the receipt of Orphan Medicinal Product > > designation from the European Medicines Agency (EMEA) for RCC. The > > Company had previously announced receipt of Orphan Drug designation > > from the U.S. Food and Drug Administration (FDA) for the same > > indication. > > > Final Phase 2 Study Results > > > The Phase 2talactoferrinmonotherapy trial was an open label, 44- > > patient, single arm trial conducted at six leading U.S. sites. To be > > eligible, patients with histologically confirmed metastatic or > > unresectable RCC had to have disease progression after being treated > > with at least one prior regimen of systemic therapy. Computed > > tomography (CT) scan documentation of disease progression following > > the most recent therapy was required.Talactoferrinwas administered > > at a dose of 1.5 grams twice a day in 14-week cycles (12 weeks on, two > > weeks off) for up to four cycles or until disease progression. The > > study's co-primary endpoints were to detect an increase in the 14-week > > progression-free survival (PFS) rate from 20% to 40% or a 12.5% > > response rate, either of which were considered to be clinically > > significant. In a Phase 2 trial of Avastin in second line RCC > > patients, the placebo arm had a 4-month PFS rate of 20%, and was > > chosen as the historical reference. > > > All 44 patients were included in the intent-to-treat (ITT) population. > > The study met the pre-defined target with a 14-week PFS rate of 59% > > (p<0.0001 for comparison to 20%). The response rate was 4.5%, with > > 70.5% of patients demonstrating stable disease for at least 8 weeks. > > The disease control (complete or partial response + stable disease) > > rate was 75%. The median PFS was 6.4 months. The median overall > > survival (OS) was 21.1 months, and the 1 year survival rate was 77%.Talactoferrinwas well tolerated with no significant hematological, > > renal or hepatic toxicities reported. In addition, there were no drug > > related serious adverse events. > > > About EMEA Orphan Medicinal Product Designation > > > The Regulation on Orphan Medicinal Products in the European Union (EU) > > provides incentives for companies developing and marketing therapies > > for rare diseases, defined as those affecting fewer than five in > > 10,000 people in the EU. The Regulation grants companies with Orphan > > Medicinal Product designation market exclusivity for a particular > > indication for a period of ten years following Marketing Authorization > > Approval by the EMEA. Orphan Medicinal Product designation also > > facilitates the drug development process by providing companies with > > protocol assistance, clinical trial support, direct access to the > > Centralized Procedure, grant funding for research, and waiver or > > reduction of application fees. > > > The Company had previously received Orphan Drug designation for RCC > > from the U.S. FDA. > > > "We are very pleased that the EMEA recognizes that our lead product,talactoferrinalfa, has potential as a treatment for patients with > > RCC, and we are planning additional trials in this indication > > including a randomized, placebo-controlled Phase 2b trial oftalactoferrinin combination with a standard first-line therapy," said > > Rajesh Malik, M.D., Chief Medical Officer of Agennix. > > > About the Planned Phase 2b First-Line Combination Therapy RCC Trial > > > Building on the results of the positive Phase 2 trial with single > > agenttalactoferrin, preparations are underway to conduct a Phase 2b > > trial in 200-250 previously untreated patients with advanced or > > metastatic RCC as part of a first-line combination therapy regimen. > > Patients will be randomly assigned to receive a standard therapy plus > > either oraltalactoferrinor placebo. The primary endpoint will be > > assessment of PFS, with additional endpoints including response rate, > > OS, and safety. > > > AboutTalactoferrinAlfa > > > Talactoferrin, a novel dendritic cell recruiter and activator (DCRA), > > is a unique recombinant form of human lactoferrin, an important > > immunomodulatory protein. > > > In 1988, scientists at Baylor College of Medicine, Houston, Texas, > > discovered a way to produce this protein in the laboratory, thus > > paving the way for testing its potential to help fight serious > > diseases that cause enormous suffering worldwide. > > > Lactoferrin, found in the highest concentration in milk, is expressed > > throughout the body in immune cells and on all body surfaces exposed > > to the external environment. Lactoferrin plays an important role in > > helping to establish the immune system, including the Gut Associated > > Lymphoid Tissue (GALT), in infants.Talactoferrinis produced in > > Aspergillus niger, a filamentous fungus, and is structurally identical > > to native human lactoferrin in all material respects, differing only > > in its glycosylation. > > > Talactoferrinis an orally administered protein that mediates its > > activity through the gut and the GALT -- the largest lymphoid organ in > > the body. It acts through a novel mechanism of dendritic cell > > recruitment and activation. Following oral administration,talactoferrinis transported by the M-cells into the small intestinal > > Peyer's Patches, where it recruits circulating immature dendritic > > cells bearing tumor antigens to the GALT and induces their maturation. > > DC maturation in the presence of > > ... > > read more »- Hide quoted text - > > - Show quoted text -
From: Marc Bissonnette on 4 Jul 2008 11:43 ironjustice <teamtanner(a)hotmail.com> fell face-first on the keyboard. This was the result: news:6cc3598c-7fe1-4910-9584-c3abcecb8cec(a)u36g2000prf.googlegroups.com: [snip drivel] > The technique, part of the burgeoning field of nutraceuticals, > involves creating nanoemulsions, or nano-sized capsules made from oil > and water. The emulsions, which are so small they are measured in > nanometers�or 1/100 of a meter� [snip drivel] 1/100 of a meter is a centimeter... A nanometer is one *billionth* - 1/1000000000 th of a meter. No wonder no one takes you seriously. -- Marc Bissonnette Looking for a new ISP? http://www.canadianisp.com Largest ISP comparison site across Canada.
From: ironjustice on 4 Jul 2008 12:24
On Jul 4, 8:43 am, Marc Bissonnette <dragnet\_@_/internalysis.com> wrote:[snip drivel] << Go eat some poutine .. Fat boy .. Latest Weapon in Fighting Cancer A novel technique for reducing tumors in rats-using nano-sized, oil- based emulsions may be the latest weapon in fighting cancer. The technique, part of the burgeoning field of nutraceuticals, involves creating nanoemulsions, or nano-sized capsules made from oil and water. The emulsions, which are so small they are measured in nanometersor 1/100 of a meterare then filled with various antioxidants or anti-cancer fighting compounds, and tests show they can reduce tumors in rats. Researchers at the University of Massachusetts Lowell injected rats with neuroblastoma, so they would develop tumors, and then treated them with nanoemulsions containing antioxidants. They found that while the rats fed in the control group continued to develop tumors, the growth rate for those fed antioxidants was actually negative 65 percent, meaning the tumors actually shrank. They had about 70 percent total tumor regression, said Professor Robert Nicolosi, director of UMass Lowells Center for Health and Disease Research. When researchers exposed melanoma cancer cells to a nanoemulsion containing curcumin, an anti-cancer compound found in turmeric, cancer cell proliferation was greatly reduced, Nicolosi said. And when they used a nanoemulsion containing tamoxifen, a drug used to fight breast cancer, they just about eliminated the ability of the cells to proliferateat least in a cell culture, Nicolosi said. Nanoemulsion delivery systems have been shown to increase the bioavailablity and efficacy of certain drugs. The advantage, particularly for some of the toxic compounds used in fighting cancer, is that less of that compound is needed to achieve the same effect. That means the patient would suffer fewer damaging side effects. Theres no question were reducing the toxicity when we use 10 to 20 times less, Nicolosi said. Umass has been using Microfluidizer materials processing equipment to develop the nutraceutical products. The equipment has helped standardize the size of the nanoemulsions, making them more commercially viable. Prior to the Microfluidizer, nanoemulsions came out in varying sizes, making them less effective and less likely to gain approval by the US Food and Drug Administration, according to Scott McMeil, director of the Nanotechnology Characterization Laboratory at SAIC-Frederick, Inc. Nanoemulsions have been around for several years, but they werent very stable. But with a Microfluidizer, it looks like its overcoming the stability issue, McNeil said. McNeil, whose company is subcontracted by the National Cancer Institute, said the FDA requires that a compound is stable before it will grant its seal of approval. Before researchers began using the Microfluidizer, the size of the various nanoemulsions might vary from five nanometers to five microns, in one solution, making the solution less stable. A company would not move forward with something that was that high risk, McNeil said. The Microfluidizer has opened up new opportunities, such as nanoemulsions. In order to create the nanoemulsion, scientists mix water, an emulsifier like lecithin, and an antioxidant or anti-cancer fighting compound, and then pour it into a Microfluidizer processor. The processor then compresses the solution and drives it through tiny microchannels, and then in a reaction chamber, it splits the solution into two streams, which collide with each other at extremely high speeds. The collision creates a nanoemulsion that has a long shelf life. Researchers, such as UMass are also using the Microfluidizer processors to create foods, beverages, and nutritional supplements that can reduce inflammation or inhibit the intestines ability to absorb cholesterol, thus reducing blood cholesterol levels as well as the risk of heart disease. Posted July 1st, 2008 Who loves ya. Tom Jesus Was A Vegetarian! http://tinyurl.com/2r2nkh Man Is A Herbivore! http://tinyurl.com/4rq595 DEAD PEOPLE WALKING http://tinyurl.com/zk9fk |