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Espaço de publicação e discussão sobre oncologia. GBM IMMUNOTHERAPY ONCO-VIRUS ONCOLOGY CANCER CHEMOTHERAPY RADIOTHERAPY


Domingo, 25.10.15

ASCO Releases Guideline Updates for the Use of Colony-stimulating Factors

ASCO Releases Guideline Updates for the Use of Colony-stimulating Factors

ASCO updates Clinical Practice Guidelines for the use of hematopoietic colony-stimulating factors.
ASCO updates Clinical Practice Guidelines for the use of hematopoietic colony-stimulating factors.

The American Society of Clinical Oncology (ASCO) has released an updated version of its Clinical Practice Guidelines on the use of hematopoietic colony-stimulating factors (CSFs), a treatment option for neutropenia, which is a major complication of myelosuppressive chemotherapy.

The updates were based on a systematic review of randomized clinical trials, meta-analyses, and systematic reviews conducted between October 2005 and September 2014 and are intended to address the limitations and strengths of using CSFs in clinical practice.1

Key guideline recommendations include:

• In patients with a greater than 20% risk of febrile neutropenia, primary prophylaxis with CSF with first and subsequent cycles of chemotherapy is recommended. The guidelines also note that regimens that do not require CSF and are equally effective should be considered as well.
• In patients with a neutropenic complication from a previous cycle of chemotherapy (without primary prophylaxis) and reduction or delay in treatment would alter outcome/survival, CSF is recommended for secondary prophylaxis. The authors note, however, that a reduction/delay may be reasonable in many situations.
• In patients with afebrile neutropenia, CSFs should not be used routinely.
• Adjunctive treatment of CSFs with antibiotics should not be routinely used for patients with febrile neutropenia. However, patients with febrile neutropenia who are considered at risk for poor outcomes or infection related-complications may be considered for adjunctive treatment with CSFs.
• The authors note that use of CSF with dose-dense regimens should only be considered when involved in a well-designed clinical trial or with support of convincing efficacy data.
• In order to mobilize peripheral-blood progenitor cells, CSFs may be used with plerixafor, after chemotherapy, or alone.
• To lessen the duration of severe neutropenia, CSFs should be given after autologous stem-cell transplants.
• To lessen the duration of severe neutropenia, CSFs may be given after allogeneic stem-cell transplants. Since the 2006 update, reports of increased risk of grade 2 to 4 graft-versus-host disease with CSF use after allogeneic transplantation have not been confirmed. The researchers note that the benefits seem to be modest with the limited amount of data.
• Patients age 65 or older, particularly those with comorbidities, with aggressive forms of diffuse lymphoma treated with curative chemotherapy should be considered for CSF prophylaxis.
• In pediatric patients, CSFs for primary prophylaxis is considered reasonable in patients at high risk for febrile neutropenia. Likewise, the guidelines note that secondary prophylaxis should be limited to patients who are high risk.
• CSFs should be used in pediatric patients to facilitate dose-intense chemotherapy regimens that are known to have survival benefits (Ewing sarcoma).
• The guidelines do not recommend using CSFs in nonrelapsed acute myeloid leukemia or nonrelapsed acute lymphocytic leukemia in pediatric patients without infection.
• There were no additional data to support a change in recommendation on treatment choice for treatment-related neutropenia. Patient's clinical situation, convenience, and cost are factors considered in the agent choice.
• The authors note a moderate recommendation for use of CSFs or pegylated granulocyte CSFs in patients exposed to lethal doses of total-body radiotherapy without evidence of impending death from organ injury.


The authors highlight the evidence that comorbid conditions increase the risk of febrile neutropenia in patients treated with chemotherapy.

 

RELATED: Consider Febrile Neutropenia Risk When Administering Standard Treatment in Prostate Cancer

Furthermore, when taking into account age and type of cancer, a patient's comorbidities continue to be an important predictor for febrile neutropenia.

Finally, the authors note that granulocyte-CSFs are expensive and questions remain to be answered on cost effectiveness. However, it is emphasized that choice of agent should be guided by the clinical scenario, not cost.

Reference

  1. Smith T, Bohlke K, Lyman G, et al. Recommendations for the use of WBC growth factors: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol.  July 13, 2015. [epub ahead of print] doi: 10.1200/JCO.2015.62.3488.

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por cyto às 19:03

Quarta-feira, 19.08.15

Unituxin (dinutuximab) granted EC Marketing Authorisation for treatment of childhood neuroblastoma

Unituxin (dinutuximab) granted EC Marketing Authorisation for treatment of childhood neuroblastoma

Published on August 17, 2015 at 7:21 AM ·

United Therapeutics Corporation (NASDAQ: UTHR) announced today that the European Commission (EC) has granted Marketing Authorisation for Unituxin™ (dinutuximab) for the treatment of high-risk neuroblastoma in patients aged 12 months to 17 years, who have previously received induction chemotherapy and achieved at least a partial response, followed by myeloablative therapy and autologous stem cell transplantation (ASCT). Unituxin is administered in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-2 (IL-2), and isotretinoin.

Neuroblastoma is the most common extracranial solid cancer in childhood and the most common cancer in infancy, with an annual incidence in the European Union of approximately 1500 patients, of whom 50% are diagnosed as having high-risk disease.

The European approval was based on demonstration of improved event-free survival (EFS) and overall survival (OS) in a multicenter, open-label, randomized trial (ANBL0032) sponsored by the US National Cancer Institute under a Cooperative Research and Development Agreement with United Therapeutics and conducted by the Children's Oncology Group (COG).

Trial design and results

The trial randomized (1:1) 226 patients to either the Unituxin/13-cis-retinoic acid (RA) arm or the RA alone arm. Patients in each arm received six cycles of treatment. The Unituxin/RA arm consisted of Unituxin in combination with granulocyte macrophage-colony stimulating factor and RA (cycles 1, 3, and 5), Unituxin in combination with interleukin-2 and RA (cycles 2 and 4), and RA (cycle 6). Patients were 11 months to 15 years of age (median age 3.8 years).

The major efficacy outcome measure was investigator-assessed EFS, defined as the time from randomization to the first occurrence of relapse, progressive disease, secondary malignancy or death. The primary intent-to-treat analysis found an improvement in EFS associated with dinutuximab immunotherapy plus isotretinoin as compared to isotretinoin alone. The two-year estimates of EFS were 66% among subjects receiving dinutuximab immunotherapy plus isotretinoin as compared with 48% in subjects receiving isotretinoin alone (log-rank test p = 0.033) although this difference did not reach formal statistical significance according to the pre-specified plan for interim analyses. In addition, OS was evaluated with 3 years of follow-up after the EFS analysis as a secondary endpoint with a significant improvement observed among ITT subjects randomly allocated to receive dinutuximab immunotherapy plus isotretinoin as compared with isotretinoin alone. The three-year estimates of OS were 80% compared with 67% among subjects receiving dinutuximab immunotherapy plus isotretinoin and isotretinoin alone, respectively (log-rank test p = 0.0165). Long-term overall survival was evaluated with five years of follow up after the EFS analysis and continued to demonstrate a survival advantage for patients who received dinutuximab immunotherapy compared to those who received isotretinoin alone. The five-year estimates of OS were 74% for dinutuximab immunotherapy compared to 57% for isotretinoin alone (log-rank test p = 0.030).

Frequently occurring adverse reactions

The most frequently occurring (more than 30% of patients) adverse reactions reported during the neuroblastoma studies were hypotension (67%), pain (66%), hypersensitivity (56%), pyrexia (53%), urticaria (49%), capillary leak syndrome (45%), anaemia (45%), hypokalaemia (41%), platelet count decreased (40%), hyponatraemia (37%), alanine aminotransferase increased (35%), decreased lymphocyte count (34%) and decreased neutrophil count (31%). Additional adverse reactions characteristic of an allergic response were also reported – including anaphylactic reaction (18%) and bronchospasm (4%).

Posology and method of administration

Unituxin is to be administered by intravenous infusion over five courses at a daily dose of 17.5 mg/m2. It is administered on days 4-7 during courses 1, 3 and 5 (each course lasting approximately 24 days) and on days 8-11 during courses 2 and 4 (each course lasting approximately 28 days).

The treatment regimen consists of Unituxin, GM-CSF, IL-2, and isotretinoin, administered over six consecutive courses.

Source:

United Therapeutics Corporation

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por cyto às 12:08

Quarta-feira, 29.07.15

ASCO Releases Guideline Updates for the Use of Colony-stimulating Factors

 

ASCO Releases Guideline Updates for the Use of Colony-stimulating Factors

 

The American Society of Clinical Oncology (ASCO) has released an updated version of its Clinical Practice Guidelines on the use of hematopoietic colony-stimulating factors (CSFs), a treatment option for neutropenia, which is a major complication of myelosuppressive chemotherapy.

The updates were based on a systematic review of randomized clinical trials, meta-analyses, and systematic reviews conducted between October 2005 and September 2014 and are intended to address the limitations and strengths of using CSFs in clinical practice.1

Key guideline recommendations include:

• In patients with a greater than 20% risk of febrile neutropenia, primary prophylaxis with CSF with first and subsequent cycles of chemotherapy is recommended. The guidelines also note that regimens that do not require CSF and are equally effective should be considered as well.
• In patients with a neutropenic complication from a previous cycle of chemotherapy (without primary prophylaxis) and reduction or delay in treatment would alter outcome/survival, CSF is recommended for secondary prophylaxis. The authors note, however, that a reduction/delay may be reasonable in many situations.
• In patients with afebrile neutropenia, CSFs should not be used routinely.
• Adjunctive treatment of CSFs with antibiotics should not be routinely used for patients with febrile neutropenia. However, patients with febrile neutropenia who are considered at risk for poor outcomes or infection related-complications may be considered for adjunctive treatment with CSFs.
• The authors note that use of CSF with dose-dense regimens should only be considered when involved in a well-designed clinical trial or with support of convincing efficacy data.
• In order to mobilize peripheral-blood progenitor cells, CSFs may be used with plerixafor, after chemotherapy, or alone.
• To lessen the duration of severe neutropenia, CSFs should be given after autologous stem-cell transplants.
• To lessen the duration of severe neutropenia, CSFs may be given after allogeneic stem-cell transplants. Since the 2006 update, reports of increased risk of grade 2 to 4 graft-versus-host disease with CSF use after allogeneic transplantation have not been confirmed. The researchers note that the benefits seem to be modest with the limited amount of data.
• Patients age 65 or older, particularly those with comorbidities, with aggressive forms of diffuse lymphoma treated with curative chemotherapy should be considered for CSF prophylaxis.
• In pediatric patients, CSFs for primary prophylaxis is considered reasonable in patients at high risk for febrile neutropenia. Likewise, the guidelines note that secondary prophylaxis should be limited to patients who are high risk.
• CSFs should be used in pediatric patients to facilitate dose-intense chemotherapy regimens that are known to have survival benefits (Ewing sarcoma).
• The guidelines do not recommend using CSFs in nonrelapsed acute myeloid leukemia or nonrelapsed acute lymphocytic leukemia in pediatric patients without infection.
• There were no additional data to support a change in recommendation on treatment choice for treatment-related neutropenia. Patient's clinical situation, convenience, and cost are factors considered in the agent choice.
• The authors note a moderate recommendation for use of CSFs or pegylated granulocyte CSFs in patients exposed to lethal doses of total-body radiotherapy without evidence of impending death from organ injury.


The authors highlight the evidence that comorbid conditions increase the risk of febrile neutropenia in patients treated with chemotherapy.

 

RELATED: Consider Febrile Neutropenia Risk When Administering Standard Treatment in Prostate Cancer

Furthermore, when taking into account age and type of cancer, a patient's comorbidities continue to be an important predictor for febrile neutropenia.

Finally, the authors note that granulocyte-CSFs are expensive and questions remain to be answered on cost effectiveness. However, it is emphasized that choice of agent should be guided by the clinical scenario, not cost.

Reference

  1. Smith T, Bohlke K, Lyman G, et al. Recommendations for the use of WBC growth factors: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol.  July 13, 2015. [epub ahead of print] doi: 10.1200/JCO.2015.62.3488.

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por cyto às 18:56

Terça-feira, 21.07.15

Patients' own genetically engineered immune cells show significant success against multiple myeloma

 

Patients' own genetically engineered immune cells show significant success against multiple myeloma

Published on July 21, 2015 at 2:37 AM 

In recent years, immunotherapy has emerged as a promising treatment for certain cancers. Now this strategy, which uses patients' own immune cells, genetically engineered to target tumors, has shown significant success against multiple myeloma, a cancer of the plasma cells that is largely incurable. The results appeared in a study published online today in Nature Medicine.

Patients received an infusion of altered immune cells known as T-cells - roughly 2.4 billion of them - after undergoing a stem cell transplantation of their own stem cells. In 16 of 20 patients with advanced disease, there was a significant clinical response. The scientists found that the T-cell therapy was generally well-tolerated and that modified immune cells traveled to the bone marrow, where myeloma tumors typically are found, and showed a long-term ability to fight the tumors. Relapse was generally associated with a loss of the engineered T-cells.

"This study suggests that treatment with engineered T-cells is not only safe but of potential clinical benefit to patients with certain types of aggressive multiple myeloma," says first author Aaron P. Rapoport, MD, the Gary Jobson Professor in Medical Oncology at the University of Maryland School of Medicine. "Our findings provide a strong foundation for further research in the field of cellular immunotherapy for myeloma to help achieve even better results for our patients."

The trial is the first published use of genetically modified T-cells for treating patients with multiple myeloma. The approach has been used to treat leukemia as well as lymphoma, according to Dr. Rapoport, who is the Director of the Blood and Marrow Transplant Program at the University of Maryland Marlene and Stewart Greenebaum Cancer Center.

More than 77,000 people in the United States have multiple myeloma, with about 24,000 new cases diagnosed each year. Patients are treated with chemotherapy and in many cases an autologous stem cell transplant, but long-term response rates are low, and median survival is three to five years.

"The majority of patients who participated in this trial had a meaningful degree of clinical benefit," Dr. Rapoport notes. "Even patients who later relapsed after achieving a complete response to treatment or didn't have a complete response had periods of disease control that I believe they would not have otherwise experienced. Some patients are still in remission after nearly three years."

The research is a collaboration between the University of Maryland School of Medicine, the Perelman School of Medicine at the University of Pennsylvania and Adaptimmune, a clinical stage biopharmaceutical company which owns the core T-cell receptor technology and funded the study. Dr. Rapoport and co-authors Edward A. Stadtmauer, MD, of the University of Pennsylvania Abramson Cancer Center, and Gwendolyn K. Binder-Scholl, PhD, of Adaptimmune, contributed equally to the research. Dr. Rapoport is the study's principal investigator.

In the clinical study, patients' T-cells were engineered to express an affinity-enhanced T-cell receptor (TCR) specific for a type of tumor antigen, or protein, known as a cancer-testis antigen (CT antigen). The target CT antigens were NY-ESO-1 and LAGE-1. Up to 60 percent of advanced myelomas have been reported to express NY-ESO-1 and/or LAGE-1, which correlates to tumor proliferation and poorer outcomes. According to Adaptimmune, the trial is the first published study of lentiviral vector mediated TCR gene expression in humans.

Of the 20 patients treated, 14 (70 percent) had a near complete or complete response three months after treatment. Median progression-free survival was 19.1 months and overall survival was 32.1 months. Two patients had a very good partial response three months post treatment. Half the patients were treated at the University of Maryland Greenebaum Cancer Center and half at the University of Pennsylvania Abramson Cancer Center. Researchers note that the response rate was better than would be expected for a standard autologous stem cell transplant. In addition, patients did not experience side effects which have been associated with another type of genetically engineered T-cells (chimeric antigen receptors, or CARS) used to treat other cancers.

The study was originally developed by Carl H. June, MD, of the University of Pennsylvania Abramson Cancer Center, and Dr. Rapoport, who have been research collaborators for 18 years.

"Multiple myeloma is a treatable but largely incurable cancer. This study reveals the promise that immunotherapy with genetically engineered T-cells holds for boosting the body's ability to attack the cancer and provide patients with better treatments and control of their disease," says E. Albert Reece, MD., PhD, MBA, vice president for medical affairs at the University of Maryland and the John Z. and Akiko K. Bowers Distinguished Professor and dean of the University of Maryland School of Medicine. "This trial is also an excellent example of significant scientific advances that result from collaborations between academic medical institutions and private industry."

Source:

University of Maryland Medical Center

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por cyto às 18:10

Sábado, 04.07.15

way to stop growth of cancer cells by targeting the Warburg Effect

SLU researchers find way to stop growth of cancer cells by targeting the Warburg Effect

Published on June 26, 2015 at 10:55 PM 

In research published in Cancer Cell, Thomas Burris, Ph.D., chair of pharmacology and physiology at Saint Louis University, has, for the first time, found a way to stop cancer cell growth by targeting the Warburg Effect, a trait of cancer cell metabolism that scientists have been eager to exploit.

Unlike recent advances in personalized medicine that focus on specific genetic mutations associated with different types of cancer, this research targets a broad principle that applies to almost every kind of cancer: its energy source.

The Saint Louis University study, which was conducted in animal models and in human tumor cells in the lab, showed that a drug developed by Burris and colleagues at Scripps Research Institute can stop cancer cells without causing damage to healthy cells or leading to other severe side effects.

The Warburg Effect

Metabolism -- the ability to use energy -- is a feature of all living things. Cancer cells aggressively ramp up this process, allowing mutated cells to grow unchecked at the expense of surrounding tissue.

"Targeting cancer metabolism has become a hot area over the past few years, though the idea is not new," Burris said.

Since the early 1900s, scientists have known that cancer cells prefer to use glucose as fuel even if they have plenty of other resources available. In fact, this is how doctors use PET (positron emission tomography) scan images to spot tumors. PET scans highlight the glucose that cancer cells have accumulated.

This preference for using glucose as fuel is called the Warburg effect, or glycolysis.

In his paper, Burris reports that the Warburg effect is the metabolic foundation of oncogenic (cancer gene) growth, tumor progression and metastasis as well as tumor resistance to treatment.

Cancer's goal: to grow and divide

Cancer cells have one goal: to grow and divide as quickly as possible. And, while there are a number of possible molecular pathways a cell could use to find food, cancer cells have a set of preferred pathways.

"In fact, they are addicted to certain pathways," Burris said. "They need tools to grow fast and that means they need to have all of the parts for new cells and they need new energy."

"Cancer cells look for metabolic pathways to find the parts to grow and divide. If they don't have the parts, they just die," said Burris. "The Warburg effect ramps up energy use in the form of glucose to make chemicals required for rapid growth and cancer cells also ramp up another process, lipogenesis, that lets them make their own fats that they need to rapidly grow."

If the Warburg effect and lipogenesis are key metabolic pathways that drive cancer progression, growth, survival, immune evasion, resistance to treatment and disease recurrence, then, Burris hypothesizes, targeting glycolysis and lipogenesis could offer a way to stop a broad range of cancers.

Cutting off the energy supply

Burris and his colleagues created a class of compounds that affect a receptor that regulates fat synthesis. The new compound, SR9243, which started as an anti-cholesterol drug candidate, turns down fat synthesis so that cells can't produce their own fat. This also impacts the Warburg pathway, turning cancer cells into more normal cells. SR9243 suppresses abnormal glucose consumption and cuts off cancer cells' energy supply.

When cancer cells don't get the parts they need to reproduce through glucose or fat, they simply die.

Because the Warburg effect is not a feature of normal cells and because most normal cells can acquire fat from outside, SR9243 only kills cancer cells and remains non-toxic to healthy cells.

The drug also has a good safety profile; it is effective without causing weight loss, liver toxicity, or inflammation.

Promising Results So far, SR9243 has been tested in cultured cancer cells and in human tumor cells grown in animal models. Because the Warburg pathway is a feature of almost every kind of cancer, researchers are testing it on a number of different cancer models.

"It works in a wide range of cancers both in culture and in human tumors developing in animal models," Burris said. "Some are more sensitive to it than others. In several of these pathways, cells had been reprogramed by cancer to support cancer cell growth. This returns the metabolism to that of more normal cells."

In human tumors grown in animal models, Burris said, "It worked very well on lung, prostate, and colorectal cancers, and it worked to a lesser degree in ovarian and pancreatic cancers."

It also seems to work on glioblastoma, an extremely difficult to treat form of brain cancer, though it isn't able to cross the brain/blood barrier very effectively. The challenge for researchers in this scenario will be to find a way to allow the drug to cross this barrier, the body's natural protection for the brain, which can make it difficult for drug treatments to reach their target.

And, in even more promising news, it appears that when SR9243 is used in combination with existing chemotherapy drugs, it increases their effectiveness, in a mechanism apart from SR9243's own cancer fighting ability.

Source:

Saint Louis University

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por cyto às 11:25

Sábado, 04.07.15

Nanoparticles packed with chemotherapy drug and coated with chitosan target cancer stem-like cells

 

Nanoparticles packed with chemotherapy drug and coated with chitosan target cancer stem-like cells

Published on July 1, 2015 at 7:35 AM ·

Nanoparticles packed with a clinically used chemotherapy drug and coated with an oligosaccharide derived from the carapace of crustaceans might effectively target and kill cancer stem-like cells, according to a recent study led by researchers at The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC - James). Cancer stem-like cells have characteristics of stem cells and are present in very low numbers in tumors. They are highly resistant to chemotherapy and radiation and are believed to play an important role in tumor recurrence. This laboratory and animal study showed that nanoparticles coated with the oligosaccharide called chitosan and encapsulating the chemotherapy drug doxorubicin can target and kill cancer stem-like cells six times more effectively than free doxorubicin.

"Our findings indicate that this nanoparticle delivery system increases the cytotoxicity of doxorubicin with no evidence of systemic toxic side effects in our animal model," says principal investigator Xiaoming (Shawn) He, PhD, associate professor of Biomedical Engineering and a member of the OSUCCC - James Translational Therapeutics Program.

"We believe that chitosan-decorated nanoparticles could also encapsulate other types of chemotherapy and be used to treat many types of cancer."

This study showed that chitosan binds with a receptor on cancer stem-like cells called CD44, enabling the nanoparticles to target the malignant stem-like cells in a tumor.

The nanoparticles were engineered to shrink, break open, and release the anticancer drug under the acidic conditions of the tumor microenvironment and in tumor-cell endosomes and lysosomes, which cells use to digest nutrients acquired from their microenvironment.

He and his colleagues conducted the study using models called 3D mammary tumor spheroids (i.e., mammospheres) and an animal model of human breast cancer.

The study also found that although the drug-carrying nanoparticles could bind to the variant CD44 receptors on cancerous mammosphere cells, they did not bind well to the CD44 receptors that were overexpressed on noncancerous stem cells.

Source:

Ohio State University Wexner Medical Center

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por cyto às 11:21

Sábado, 04.07.15

new immunotherapy treatment for cancer patients

 

CTCA at Western begins Phase Ib/II trial of new immunotherapy treatment for cancer patients

Published on June 27, 2015 at 2:15 AM · 

Cancer Treatment Centers of America® (CTCA) at Western Regional Medical Center (Western) in Goodyear, Arizona, has begun a new Phase Ib/II clinical trial using a new immunotherapy treatment for patients with advanced kidney, non-small cell lung cancer, pancreatic cancer and colorectal carcinoma.

This "NivoPlus" clinical trial combines an immunotherapy drug (nivolumab) with already FDA-approved chemotherapy drugs (temsirolimus, irinotecan, and a combination of irinotecan and capecitabine).

The addition of nivolumab is intended to activate the body's own immune system to improve on the results that otherwise might not be achieved from chemotherapy alone. This combination of chemotherapy and immunotherapy drugs is investigational in this study and is the third such combination clinical trial launched in the past year by CTCA® at Western.

There are anticipated to be up to 49 patients enrolled on the multi-arm NivoPlus study. The first patient received treatment on this study earlier this month.

"Some of these drug combinations are not available elsewhere, giving CTCA patients additional treatment options," said Dr. Glen Weiss, Director of Clinical Research and Medical Oncologist, CTCA at Western. "Our ultimate goal is to evaluate if these combinations yield improved results for our patients."

Nivolumab works by inhibiting a protein called PD-1, which otherwise blocks the body's immune system from attacking cancerous cells.

Nivolumab was approved by the Food and Drug Administration in December 2014 for the treatment of advanced melanoma and on March 4, 2015, for patients with previously treated metastatic squamous non-small cell lung cancer.

"Patients with these types of advanced-stage cancers have tumors that may be challenging to treat," said Dr. Vivek Khemka, Medical Oncologist, CTCA Western and NivoPlus Principal Investigator. "We are investigating whether combining nivolumab with these chemotherapy drugs will be a more powerful approach against their disease."

Recent data reported in the New England Journal of Medicine and Lancet demonstrates promising results with antibody-based immunostimulatory therapy in treating melanoma, renal cell carcinoma, non-small cell lung cancer and colorectal cancer. Data has also shown synergetic effects of utilizing cytotoxic chemotherapy in combination with immunostimulatory therapy. NivoPlus will build upon this data, extending treatment options to additional cancer types.

CTCA investigators have been actively researching the impact of immunotherapy, a topic prominently highlighted this year at the annual conferences of both the American Association for Cancer Research (AACR) and the American Society of Clinical Oncologists (ASCO).

At AACR, physicians described immunotherapy as now being considered an integral part of cancer biology and cancer treatment, and recent clinical successes were described as "stunning" and "unprecedented" in their ability to improve the care of cancer patients.

At ASCO, a full press briefing was devoted to the subject of immunotherapy, which was described by doctors as "one of the most exciting advances in oncology," enabling the body's own immune system to target cancer tumors and key to helping accelerate the pace of progress "and ultimately achieve cures for cancer."

Additionally, in 2013, Science magazine named cancer immunotherapy the scientific breakthrough of the year.

CTCA physicians are committed to bringing the latest technologies and advanced treatment options to their patients as quickly as possible. At the same time, CTCA patients are supported with therapies to reduce side effects, boost energy levels and keep them strong during treatment.

Source:

Cancer Treatment Centers of America

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por cyto às 11:18

Quinta-feira, 02.07.15

CTCA at Western begins Phase Ib/II trial of new immunotherapy treatment for cancer patients

CTCA at Western begins Phase Ib/II trial of new immunotherapy treatment for cancer patients

Published on June 27, 2015 at 2:15 AM · 

Cancer Treatment Centers of America® (CTCA) at Western Regional Medical Center (Western) in Goodyear, Arizona, has begun a new Phase Ib/II clinical trial using a new immunotherapy treatment for patients with advanced kidney, non-small cell lung cancer, pancreatic cancer and colorectal carcinoma.

This "NivoPlus" clinical trial combines an immunotherapy drug (nivolumab) with already FDA-approved chemotherapy drugs (temsirolimus, irinotecan, and a combination of irinotecan and capecitabine).

The addition of nivolumab is intended to activate the body's own immune system to improve on the results that otherwise might not be achieved from chemotherapy alone. This combination of chemotherapy and immunotherapy drugs is investigational in this study and is the third such combination clinical trial launched in the past year by CTCA® at Western.

There are anticipated to be up to 49 patients enrolled on the multi-arm NivoPlus study. The first patient received treatment on this study earlier this month.

"Some of these drug combinations are not available elsewhere, giving CTCA patients additional treatment options," said Dr. Glen Weiss, Director of Clinical Research and Medical Oncologist, CTCA at Western. "Our ultimate goal is to evaluate if these combinations yield improved results for our patients."

Nivolumab works by inhibiting a protein called PD-1, which otherwise blocks the body's immune system from attacking cancerous cells.

Nivolumab was approved by the Food and Drug Administration in December 2014 for the treatment of advanced melanoma and on March 4, 2015, for patients with previously treated metastatic squamous non-small cell lung cancer.

"Patients with these types of advanced-stage cancers have tumors that may be challenging to treat," said Dr. Vivek Khemka, Medical Oncologist, CTCA Western and NivoPlus Principal Investigator. "We are investigating whether combining nivolumab with these chemotherapy drugs will be a more powerful approach against their disease."

Recent data reported in the New England Journal of Medicine and Lancet demonstrates promising results with antibody-based immunostimulatory therapy in treating melanoma, renal cell carcinoma, non-small cell lung cancer and colorectal cancer. Data has also shown synergetic effects of utilizing cytotoxic chemotherapy in combination with immunostimulatory therapy. NivoPlus will build upon this data, extending treatment options to additional cancer types.

CTCA investigators have been actively researching the impact of immunotherapy, a topic prominently highlighted this year at the annual conferences of both the American Association for Cancer Research (AACR) and the American Society of Clinical Oncologists (ASCO).

At AACR, physicians described immunotherapy as now being considered an integral part of cancer biology and cancer treatment, and recent clinical successes were described as "stunning" and "unprecedented" in their ability to improve the care of cancer patients.

At ASCO, a full press briefing was devoted to the subject of immunotherapy, which was described by doctors as "one of the most exciting advances in oncology," enabling the body's own immune system to target cancer tumors and key to helping accelerate the pace of progress "and ultimately achieve cures for cancer."

Additionally, in 2013, Science magazine named cancer immunotherapy the scientific breakthrough of the year.

CTCA physicians are committed to bringing the latest technologies and advanced treatment options to their patients as quickly as possible. At the same time, CTCA patients are supported with therapies to reduce side effects, boost energy levels and keep them strong during treatment.

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por cyto às 11:56

Segunda-feira, 18.05.15

new strategy to combat cancer

CNIO researchers identify new strategy to combat cancer

Published on May 14, 2015 at 4:23 AM · 

Scientists from the Spanish National Cancer Research Centre (CNIO) have discovered a new strategy to fight cancer, which is very different from those described to date. Their work shows for the first time that telomeres -- the structures protecting the ends of the chromosomes -- may represent an effective anti-cancer target: by blocking the TRF1 gene, which is essential for the telomeres, they have shown dramatic improvements in mice with lung cancer.

"Telomere uncapping is emerging as a potential mechanism to develop new therapeutic targets for lung cancer," mention the authors with equal contribution in EMBO Molecular Medicine; Maria Garcia-Beccaria, Paula Martinez and Marinela Mendez, from the CNIO Telomeres and Telomerase Group led by Maria Blasco, who is also an author in the article. The research was also carried out in collaboration with the Experimental Therapeutics Programme, the Experimental Oncology Group and the Histopathology, Molecular Imaging and Microscopy Units at the CNIO, as well as with the Animal Medicine and Surgery Department at the Universidad Complutense de Madrid.

Every time a cell divides, it must duplicate its genetic material, the DNA, which is packed inside the chromosomes. However, given how the mechanism of DNA replication works, the end of each chromosome cannot be replicated completely, and, as a result, telomeres shorten with each cell division. Excessively short telomeres are toxic to cells, which stop replicating, and eventually, the cells are eliminated by senescence or apoptosis.

This phenomenon has been known for decades, as well as the fact that it usually does not occur in tumour cells. Cancer cells proliferate without any apparent limits, and therefore, they are constantly dividing, but their telomeres do not gradually become shorter; the key behind this mechanism is that the telomerase enzyme in cancer cells remains active, while in most healthy cells telomerase is turned off. The constant repair of telomeres by telomerase is, in fact, one of the mechanisms that allows tumour cells to be immortal and divide endlessly.

Hence, an obvious strategy to fight cancer is to inhibit the telomerase enzyme in tumour cells. This approach has been tested before, but with worrisome results: telomeres do shorten, but this shortening is lethal to tumour cells only after a variable number of cell divisions necessary for telomeres to become completely eroded-- thus the effects are not instantly seen.

In the study now published, the researchers also target telomeres, but their approach is completely different from the telomerase one.

A NEW APPROACH FOR THE ACUTE TELOMERE UNCAPPING

Telomeres are made up of repeating patterns of DNA sequences that are repeated hundreds of times -- this is the structure that shortens with each cellular division. Telomere DNA is bound by a six-protein complex, called shelterin (from the term shelter or protection), which forms a protective covering. The CNIO team strategy consisted of blocking one of the shelterins, namely TRF1, so that that the telomere shield was destroyed.

The idea of targeting one of the shelterins has not been tried so far, due to the fear of encountering many toxic effects caused by acting on these proteins that are present in both healthy and tumour cells.

"Nobody had explored the idea of using one of the shelterins as an anti-cancer target," explains Blasco. "It is difficult to find drugs that interfere with protein binding to DNA, and the possibility exists that drugs targeting telomere caps could be very toxic. For these reasons, no one had explored this option before, although it makes a lot of sense."

FEWER THAN EXPECTED SIDE-EFFECTS

The present work subtitled 'Shelterin as a novel target in cancer,' shows that blocking TRF1 only causes minor toxicities that are well tolerated by mice. "It does however prevent the growth of lung carcinomas already developed in mice," write the authors inEMBO Molecular Medicine.

"TRF1 removal induces an acute telomere uncapping, which results in cellular senescence or cell death. We have seen that this strategy kills cancer cells efficiently, stops tumour growth and has bearable toxic effects," explains Blasco.

TRF1 has been inhibited both genetically -- in mice where the gene has been removed -- and chemically using selected compounds from CNIO's proprietary collection of active compounds. These compounds, including the inhibitor ETP-470037 developed by the CNIO Experimental Therapeutics Programme, may provide a starting point for the development of new drugs for cancer therapy.

"We've shown that we can find potential drugs able to inhibit TRF1 that have therapeutic effects when administered orally to mice," says Blasco.

A CANCER WITH NO CURRENTLY AVAILABLE THERAPEUTIC TARGETS

The scientists worked with mouse models for lung cancer, the cancer type that has the highest death rates worldwide. Specifically, they used a mouse with a very aggressive type of lung cancer for which no drug targets have been found to date: the tumours have an active K-Ras oncogene and the p53 tumor suppressor is missing. TRF1 is the first target that is able to inhibit the growth of these highly aggressive tumours.

The work process has been long. The researchers first selected TRF1 among the shelterin family. TRF1 is one of the most studied shelterins that is present exclusively at the telomeres and has potential as a good anti-cancer target -- its inhibition also affects the so-called cancer stem cells that might be responsible for tumour recurrence over time.

The next aim was to demonstrate that TRF1 is really an anti-cancer target. To do so, the researchers genetically blocked its activity in mice with lung cancer as well as in healthy mice, in order to test the toxicity of the procedure.

Having established the effectiveness and low toxicity of the new target, the researchers searched for chemical compounds that could have activity against TRF1. Two types of compounds have been found. "We are now looking for partners in the pharmaceutical industry to bring this research into more advanced stages of drug development," says Blasco.

Source:

Centro Nacional de Investigaciones Oncologicas (CNIO)

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por cyto às 13:46


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