Saltar para: Posts [1], Pesquisa e Arquivos [2]

http://cyto.blogs.sapo.pt

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



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.

Autoria e outros dados (tags, etc)

por cyto às 18:56

Quarta-feira, 29.07.15

Frequent, Actionable MET Gene Mutations Found in Pulmonary Sarcomatoid Carcinoma

 

Frequent, Actionable MET Gene Mutations Found in Pulmonary Sarcomatoid Carcinoma

Mutational events that lead to MET exon 14 skipping may be targetable events in pulmonary sarcomatoid carcinoma.
Mutational events that lead to MET exon 14 skipping may be targetable events in pulmonary sarcomatoid carcinoma.

Mutational events that lead to MET exon 14 skipping occur frequently and may be targetable events in patients with pulmonary sarcomatoid carcinoma (PSC), according to a recent study published online ahead of print in the Journal of Clinical Oncology.

Balazs Halmos, MD, of Columbia University Medical Center, in New York, NY, and fellow researchers conducted whole-exome sequencing as well as targeted METmutation screening in patients with PSC in order to further understand molecular pathogenesis of the disease.

With regard to MET exon 14 skipping,, which was validated through reverse transcriptase polymerase chain reaction and Western blotting , they also performed functional studies for validation of its oncogenic roles in lung adenosquamous cell line H596 as well as gastric adenocarcinoma cell line Hs746T.

The researchers found and validated several novel mutations in genes that had since been unknown to be cancer-associated, including RASA1, CDH4, CDH7, LAMB4, SCAF1, and LMTK2. They also confirmed mutations in genes that were previously known, such as TP53, KRAS, PIK3CA, MET,NOTCH, STK11, and RB1.

 

RELATED: Greatest EGFR Prevalence in Women with Adenocarcinoma with No Smoking History

Mutations that led to exon 14 skipping were identified in eight out of 36 patient cases.

Furthermore, RNA silencing of MET and MET inhibition with crizotinib demonstrated an effect on cell viability and a decrease in downstream AKT and mitogen-activated protein kinase activation inHs746T and Hh596.

Reference

  1. Liu X, Jia Y, Stoopler MB, et al. Next-generation sequencing of pulmonary sarcomatoid carcinoma reveals high frequency of actionable MET gene mutations. Journal of Clinical Oncology. 2015. [epub ahead of print]. doi: 10.1200/JCO.2015.62.0674.

Autoria e outros dados (tags, etc)

por cyto às 18:51

Quarta-feira, 29.07.15

Brain - Reaching the right size

 

Brain - Reaching the right size

Mutations in a protein involved in neuronal proliferation and survival cause extreme brain malformations and atrophy

Published online 29 July 2015

Magnetic resonance image of the brain of an individual with the brain formation disorder microlissencephaly.

Reprinted from Ref. 1, Copyright 2014, with permission from Elsevier.

A gene responsible for a severe form of the brain formation disorder microlissencephaly has been identified by A*STAR scientists through a collaboration with researchers in seven countries1.

Microlissencephaly is a neuronal development disorder characterized by smaller brains having fewer neurons than normally developed brains (see image). Researchers, including Bruno Reversade from the A*STAR Institute of Medical Biology, identified three Middle Eastern families with children affected by the disorder who did not have mutations in any of the genes already known to cause microlissencephaly. Because some of the families had a history of marriages between closely related individuals, such as first cousins, the causative gene was believed to be passed on by both parents. By sequencing regions that were identical in the affected individuals of a particular family, the researchers were able to home in on mutations in the KATNB1 gene, as these mutations were absent in unaffected individuals in other populations.

The protein encoded by KATNB1 is part of a complex responsible for severing structural proteins in the cell called microtubules. A structure called the centrosome is known to play a central role in organizing microtubules in the cell, and many centrosomal proteins have previously been linked to patients with microlissencephaly.

To determine the function of KATNB1 during development, Reversade and his colleagues generated mice and fish lacking the Katnb1 gene — the mouse and fish analogue of KATNB1. The animal models showed defective proliferation of neuronal progenitor cells, loss of many cell types that rely on normal cell division, enhanced cell death and thinner brains. Also, cells derived from humans with microlissencephaly showed many abnormalities in cell division, such as centromeres that were abnormally placed, chromosomes that did not line up properly and cells with too many chromosomes.

Centromeres are made up of paired structures called centrioles and play a key role in forming hair-like extensions of the cell called cilia. The researchers found that cells from mice lackingKatnb1 contained many more centrioles than normal cells and that these centrioles were often unpaired. Moreover, the cells lacking this gene contained many more cilia than normal, which the researchers argue could mean that signaling regulated by cilia is defective. These dysfunctional processes probably contribute to the abnormal neuronal development observed in organisms lacking KATNB1.

“Our discovery of the causative gene for this disease will benefit families as we are now able to provide premarital and prenatal diagnosis for parents,” explains Reversade.

 

The A*STAR-affiliated researchers contributing to this research are from the Institute of Medical Biology and the Institute of Molecular and Cellular Biology. More information about the group’s research can be found at theHuman Genetics and Embryology Group webpage.

 

Related Links

Developmental biology: How a protein collaboration builds the brain

Molecular biology: Fragile interactions and brain function

Cell biology: Taking advantage of defects in splicing

 

 

Reference

  1. Hu, W. F., Pomp, O., Ben-Omran, T., Kodani, A. & Henke, K. et al. Katanin p80 regulates human cortical development by limiting centriole and cilia number. Neuron 84, 1240–1257 (2014). | article

Autoria e outros dados (tags, etc)

por cyto às 11:41

Quarta-feira, 29.07.15

A speedy test for bladder cancer

 

A speedy test for bladder cancer

A novel assay for screening urinary biomarkers employs two advanced technologies

Published online 14 January 2015

Schematic representation of antigens (red) binding onto antibody-conjugated osmium carbonyl clusters (green and purple) on bimetallic film over nanoparticles (yellow).

© 2014 A*STAR Singapore Bioimaging Consortium

A fast and accurate urine test for bladder cancer developed by A*STAR researchers has the potential to replace the currently used invasive physical probe.

Cystoscopy — a clinical procedure that uses a narrow, tubular optical instrument called a cystoscope to view inside the bladder — is currently the gold standard for detecting cancer in this organ. However, the technique is not favored by most patients because it is invasive, expensive and time consuming.

Malini Olivo at the A*STAR Singapore Bioimaging Consortium and co-workers have now developed a rapid immunoassay to detect and quantify alpha-1 antitrypsin (A1AT)1, a recently discovered urinary antigen and a potential biomarker for bladder cancer. The new tool could be used as a high-throughput screening platform to identify patients at risk of developing the urologic condition.

The immunoassay employs two advanced technologies, namely surface-enhanced Raman scattering (SERS), a powerful spectroscopic technique for detecting analytes at low concentrations, and bimetallic film over nanoparticles, a planar substrate for enhancing SERS signals. Together these technologies help to overcome interfering signals from the matrix background such as proteins in urine. The bimetallic film over nanoparticles is also coated with osmium carbonyl clusters to which target-seeking antibodies can be conjugated for assaying A1AT (see image).

The researchers first tested the immunoassay on a series of standard solutions containing A1AT antigens at various concentrations in the range 10 to 1,000 nanograms per milliliter. They observed a ‘fingerprint’ of A1AT antigens — a spectral change in the 1,850 to 2,130 cm−1 region that increases with concentration.

The scientists then tried the immunoassay on urine samples from nine patients. They found significantly elevated levels of A1AT in bladder cancer patients. There was also a marked difference in the A1AT concentrations of cancer and non-cancer patients, which suggests that the technique is highly discriminative, specific and accurate. Importantly, only tiny amounts of sample were required: A1AT concentrations could be quantified using as little as ten microliters of urine.

Compared to conventional immunoassays, the SERS-based bioassay has two practical advantages: the low-volume sample requires no purification prior to testing and the device has a simple design.

With further developments, the device may help save the lives of millions of would-be patients.

“We have developed a smart SERS biosensor for the rapid screening of bladder cancer,” says Olivo. “Our device is extremely versatile because, in theory, the osmium carbonyl clusters can be swapped with other metal carbonyl species to account for different needs and purposes.”

 

The A*STAR-affiliated researchers contributing to this research are from the Singapore Bioimaging Consortium. More information about the group’s research can be found at the Bio-optical Imaging Group webpage.

 

Related Links 

Medical diagnostics: Sweet sensing

Microelectronics: Automating cancer detection

Bioimaging: Targeting tumors with sound and vision

 

Reference

  1. Kong, K. V., Leong, W. K., Lam, Z., Gong, T., Goh, D. et al. A rapid and label-free SERS detection method for biomarkers in clinical biofluids. Small 10, 5030–5034 (2014). | article

Autoria e outros dados (tags, etc)

por cyto às 11:37

Quarta-feira, 29.07.15

Imaging probe yields double insight

 

Imaging probe yields double insight

A probe enables tumors to be investigated using complementary imaging techniques

Published online 29 July 2015

A new probe enables multimodal imaging based on photoacoustic imaging and surface-enhanced Raman scattering for studying cancer in living mice.

© vitanovski/iStock/Thinkstock

An organic dye that can light up cancer cells for two powerful imaging techniques providing complementary diagnostic information has been developed and successfully tested in mice by A*STAR researchers1.

Imaging tumors is vitally important for cancer research, but each imaging technique has its own limitations for studying cancer in living organisms. To overcome the limitations of individual techniques, researchers typically employ a combination of various imaging methods — a practice known as multimodal imaging. In this way, they can obtain complementary information and hence a more complete picture of cancer.

Two very effective methods for imaging tumors are photoacoustic imaging and surface-enhanced Raman scattering (SERS). Photoacoustic imaging can image deep tissue with a good resolution, whereas SERS detects miniscule amounts of a target molecule. To simultaneously use both photoacoustic imaging and SERS, a probe must produce signals for both imaging modalities.

In multimodal imaging, researchers typically combine probes for each imaging modality into a single two-molecule probe. However, the teams of Malini Olivo at the A*STAR Singapore Bioimaging Consortium and Bin Liu at the A*STAR Institute of Materials Research and Engineering, along with overseas collaborator Ben Zhong Tang from the Hong Kong University of Science and Technology, adopted a different approach — they developed single-molecule probes that can be used for both photoacoustic imaging and SERS. The probes are based on organic cyanine dyes that absorb near-infrared light, which has the advantage of being able to deeply penetrate tissue, enabling tumors deep within the body to be imaged.

Once the team had verified that the probes worked for both imaging modalities, they optimized the performances of the probes by adding gold nanoparticles to them to amplify the SERS signal and by encapsulating them in the polymer polyethylene glycol to stabilize their structures.

The researchers then deployed these optimized probes in live mice. By functionalizing the probes with an antibody that recognizes a tumor cell-surface protein, they were able to use them to target tumors. The scientists found that, in photoacoustic imaging, the tumor-targeted probes produced signals that were roughly three times stronger than those of unmodified probes. Using SERS, the team was also able to monitor the concentrations of the probes in the tumor, spleen and liver in real time with a high degree of sensitivity.

U. S. Dinish, a senior scientist in Olivo’s group, recalls the team’s “surprise at the sensitivity and potential of the nanoconstruct.” He anticipates that the probe could be used to guide surgical removal of tumors.

 

The A*STAR-affiliated researchers contributing to this research are from the Singapore Bioimaging Consortium and the Institute of Materials Research and Engineering

 

Related Links

Bioimaging: Exposing breast cancer using nanoscale polymers

Bioassays: A speedy test for bladder cancer

Nanoparticles: Shaken, not stirred, is best for cancer imaging 

 

Reference

  1. Dinish, U. S., Song, Z., Ho, C. J. H., Balasundaram, G., Attia, A. B. E. et al. Single molecule with dual function on nanogold: Biofunctionalized construct for in vivo photoacoustic imaging and SERS biosensing. Advanced Functional Materials 25, 2316–2325 (2015). | article

Autoria e outros dados (tags, etc)

por cyto às 11:26

Quarta-feira, 29.07.15

Cannabis May Reduce Pain in Diabetic Peripheral Neuropathy

 

Inhaling Cannabis May Reduce Pain in Diabetic Peripheral Neuropathy

 

Patients diagnosed with diabetic peripheral neuropathy may have an alternative treatment to managing pain if dosages are examined more closely -- medical cannabis. 

About 50% of patients with diabetes are suffering from diabetic peripheral neuropathy, which can be present in a multiple forms.1 Some common symptoms include: hyperalgesia, numbness, paresthesia, sensitivity to touch, unsteadiness and weakness.

Published in the Journal of Pain, a new study revealed that inhaling cannabis relieves pain resulting from neuropathy — but there's a catch.2

Researchers found that there's a dose-dependant reduction in pain. Higher doses caused more sedation and euphoria in patients suffering from diabetic peripheral neuropathy pain.2

"There is some uncertainty regarding the dosing range that results in analgesia after administration of cannabis," the authors wrote in the study.

Study author Mark Steven Wallace, MD, told Clinical Pain Advisor that “there have been very few studies looking at different doses.”

"Most studies used single doses with inconsistencies between results," said Wallace, chair of the Division of Pain Medicine in the Department of Anesthesiology at UCSanDiego Health, an academic health system. "One study using experimental pain in healthy volunteers showed that medium doses of cannabis were effective in relieving pain whereas high doses actually increased pain."

In Wallace's randomized, double-blinded, placebo-controlled crossover study, researchers sampled 16 patients with  diabetic peripheral neuropathy to analyze both the tolerability and short-term efficacy of inhaled cannabis.

Each participant was exposed to placebo or cannabis in four sessions, separated by two weeks. Dosage amounts varied for those who were administered aerosolized cannabis. Researchers gave participants a low (1% THC), medium (4% THC), or high (7% THC) dose of cannabis. Pain intensity and subject "highness" scores were measured at various intervals. Researchers measured highness by asking participants to rank how "high" they felt on a 10-point scale (0 being "not high at all").

"It is unclear on the balance between the positive (pain relieving effects) and the negative," Wallace noted. "However, there was actually minimal effects on psychomotor testing."

His team measured psychomotor speed, attention and cognitive sequencing using what's known as the Trail Making Test, a neuropsychological test consisting of visual attention and task switching. Researchers, using the Paced Auditory Serial Attention Test (PASAT), also measured participant attention, working memory and information processing speed.

"Cannabis does not treat the underlying disease process of diabetic neuropathy,” he said. “It will not prevent the progression of the disease nor will it reverse the process. It only relieves the pain that results from the neuropathy.

As for pain specialists using medical marijuana for chronic pain, many questions still remain. What can this treatment be used for? Up until May of this year, about 15 trials of medical cannibinoids have been conducted worldwide. These findings indicated effectiveness in reducing pain in patients with cancer, diabetes, fibromyalgia and neuropathy.

One lingering question that hasn't been answered: Should physicians be allowed to prescribe medical cannabis to children? While nearly 65% of Americans approve of medical marijuana use for adults, only 36% agree that medical marijuana should be available for children, according to one report.3 The majority of survey respondents also noted that medical cannabis should not be used in front of children who are under the age of 18. When children do use the drug, however, it's typically not inhaled -- it's normally available in liquid, non-psychoactive form, such as the cannabinoid cannabidiol (CBD).

More recently, a recent study in JAMA concluded that there was moderate-quality evidence suggesting that cannabinoids could benefit those with chronic neuropathic or cancer pain. The study also revealed, however, that there was low-quality evidence for no effect on psychosis. There was very low-level evidence that cannabinoids affected depression.

"More studies are needed on chronic delivery," Wallace said. "And more studies are needed on cannabidiol (the non psychoactive component of marijuana). Our study used cannabis that had very low levels of cannabidiol."

References

  1. Tesfaye S, et al. Painful Diabetic Polyneuropathy. 2015; doi: 10.1007/978-1-4614-6299-6_13.
  2. Wallace M, et al. J. Pain. 2015; doi: 10.1016/j.jpain.2015.03.008.
  3. Uofmhealth.org. Most Americans say medical marijuana shouldn't be used by kids or in front of kids – legal or not | University of Michigan Health System. 2015. Accessed July 22, 2015.
 

Autoria e outros dados (tags, etc)

por cyto às 11:21

Segunda-feira, 27.07.15

New Drug Approvals Bring Hope, Challenges in the Treatment of Chronic Leukemia

New Drug Approvals Bring Hope, Challenges in the Treatment of Chronic Leukemia

 
The approvals of obinutuzumab, ibrutinib, and idelalisib provide clinicians with new treatment options for patients with CLL.

The paradigm of the treatment of chronic lymphocytic leukemia (CLL) has shifted, with the recent addition of obinutuzumab, idelalisib, and ibrutinib to the armamentarium.

 “These agents underscore our advancement in the understanding of the biology of CLL and will improve outcomes for many patients with CLL,” wrote David S. Sanford, MD, of The University of Texas MD Anderson Cancer Center in Houston, TX, and colleagues in Clinical Lymphoma, Myeloma, and Leukemia.1

Obinutuzumab

Approved by the U.S. Food and Drug Administration (FDA) in November 2013 in combination with chlorambucil for treatment-naïve patients with CLL, obinutuzumab is a humanized type II immunoglobulin G1 antibody that targets CD20. Its cytotoxic effect is likely a result of antibody-dependent cell-mediated toxicity.2

The front-line efficacy was demonstrated in the randomized, open-label, phase 3 CLL11 trial, in which obinutuzumab plus chlorambucil resulted in greater complete (20.7% vs. 7.0%) and molecular response rates compared with rituximab plus chlorambucil.3

In addition, treatment with chlorambucil resulted in a prolonged median progression-free survival (PFS) of 26.7 months compared with 16.3 months in the rituximab plus chlorambucil arm (hazard ratio [HR], 0.44; 95% CI, 0.34 to 0.57; P<0.001) and 11.1 months in the chlorambucil monotherapy arm (HR, 0.18; 95% CI, 0.13 to 0.24; P<0.001).

In addition, overall survival (OS) was significantly greater in the obinutuzumab arm compared with chlorambucil monotherapy (HR, 0.41; 95% CI, 0.23 to 0.74; P=0.002), but was not significant compared with the rituximab arm (HR, 0.66; 95% CI, 0.41 to 1.06; P=0.08).

Median OS has not yet been reached. However, the improved efficacy with obinutuzumab did not carry over to patients with 17p deletion.

The addition of obinutuzumab did result in greater rates of adverse events (AEs) including grade 3 to 4 neutropenia and thrombocytopenia, but rates of infection were similar compared with the addition of rituximab.3

In addition, 20% of patients experienced infusion-site reactions during their first infusion of obinutuzumab, compared with 4% of patients who received rituximab.

Furthermore, patients in the obinutuzumab arm were more likely to discontinue therapy compared with the rituximab or chlorambucil monotherapy arms.

Ibrutinib

Ibrutinib was approved by the FDA in February 2014 for the treatment of patients with CLL whose disease did not respond to at least one prior therapy.

Ibrutinib is an irreversible Bruton tyrosine kinase (BTK) inhibitor, leading to the decreased activity of downstream signaling events and, ultimately, the proliferation of leukemic cells.4,5

Furthermore, ibrutinib has been shown to suppress the expression adhesion proteins in the bone marrow microenvironment, impairing B-cell homing.6

The efficacy of ibrutinib in relapsed and heavily pretreated patients with CLL was demonstrated in a multicenter, nonrandomized, open-label, phase 1b/2 trial.7

In this trial, the overall response rate was 71% in both the 420-mg and 840-mg arms. Importantly, the response rate among patients with a 17p deletion was similar at 68%; however, patients with a mutated immunoglobulin variable-region heavy-chain (IGHV) gene had a significantly lower response rate (P=0.005).

The PFS and OS rates were 75% and 83%, respectively, at 26 months. In addition, among patients with the 17p deletion, the 26-month PFS rate was 57% and OS rate was 70%.

The most common AEs included diarrhea, upper respiratory tract infection, and fatigue. Pneumonia, dehydration, and neutropenia were the most common grade 3 or higher AEs.

The phase 2 RESONATE-17 trial further demonstrated ibrutinib's efficacy in patients with a 17p deletion.8 In this nonrandomized trial, patients with relapsed CLL or small lymphocytic leukemia (SLL) with a 17p deletion received ibrutinib monotherapy for a median follow-up of 13 months. The 12-month PFS rate was 79.3%, and the median duration of response had not yet been reached.

Idelalisib

In July 2015, the FDA approved the use of idelalisib in combination with rituximab in patients with relapsed CLL in whom rituximab monotherapy is considered appropriate due to the presence of comorbidities. Idelalisib specifically and reversibly binds to the p110δ isoform of PI3 kinase (PI3K), reducing the phosphorylation of downstream signaling factors such as Akt. As a result, the tumor microenvironment within the bone marrow and chemokine signaling is disrupted, thereby promoting apoptosis of leukemic cells.9,10

A randomized, double-blind, phase 3 trial demonstrated that idelalisib plus rituximab improved overall response rates compared with placebo plus rituximab.11 Median PFS was not reached in the idelalisib arm, but was 5.5 months in the placebo arm (HR, 0.15; P<0.001). In addition, the 12-month OS rate was 92% in the idelalisib arm compared with 80% in the placebo arm (HR, 0.21; P=0.02).

A second interim analysis of the trial demonstrated that the addition of idelalisib improved PFS for patients with unfavorable cytogenetics, including a 17p deletion, TP53 mutation, or ZAP70 positivity.12

Furthermore, a nonrandomized, open-label, phase 2 extension of study 101-08 of front-line idelalisib monotherapy resulted in a 90% response rate.13

Serious AEs were more common in the idelalisib arm, and the most common AEs included diarrhea, nausea, pyrexia, fatigue, and chills. Anemia, neutropenia, thrombocytopenia, and liver enzyme elevation were more common in the idelalisib arm compared with the placebo arm.

New Options for High-risk CLL

Ibrutinib and idelalisib demonstrated efficacy in patients with CLL who harbor a chromosome 17p deletion—a feature that is notorious for difficult to treat disease, as chemoimmunotherapy typically elicits low response rates compared with wild-type 17p.13

As a result, ibrutinib is recommended by the National Comprehensive Cancer Network as the preferred first-line agent for patients with a 17p deletion. Obinutuzumab plus chlorambucil may also be used as first-line therapy, and idelalisib with or without rituximab is recommended for relapsed or refractory disease.

Incorporating into Practice

The approval of obinutuzumab, ibrutinib, and idelalisib, as well as potential approvals of additional novel, targeted agents in the future provide clinicians with new and improved options for patients with CLL. However, how to best incorporate them into clinical practice remains a challenge.

For example, clinicians may be surprised at the extent of lymphocytosis that may occur in patients that receive one of these agents; however, lymphocytosis is generally asymptomatic and slowly normalizes.

“Many questions remain about their use including long-term efficacy, safety, and how and when to best incorporate these treatments into therapy,” wrote Dr. Sanford and colleagues.1

 

References

  1. Sanford DS, Wierda WG, Burger JA, et al. Three newly approved drugs for chronic lymphocytic leukemia: incorporating ibrutinib, idelalisib, and obinutuzumab into clinical practice. Clin Lymphoma Myeloma Leuk. 2015;15(7):385-391.
  2. Beers SA, Chan CH, French RR, et al. CD20 as a target for therapeutic type I and II monoclonal antibodies. Semin Hematol. 2010;47(2):107-114.
  3. Goede V, Fischer K, Busch R, et al. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N Engl J Med. 2014;370(12):1101-1110.
  4. Honigberg LA, Smith AM, Sirisawad M, et al. The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy. Proc Natl Acad Sci USA. 2010;107(29):13075-13080.
  5. Cheng S, Ma J, Guo A, et al. BTK inhibition targets in vivo CLL proliferation through its effects on B-cell receptor signaling activity. Leukemia. 2014;28(3):649-657.
  6. Chang BY, Francesco M, De Rooij MF, et al. Egress of CD19(þ)CD5(þ) cells into peripheral blood following treatment with the Bruton tyrosine kinase inhibitor ibrutinib in mantle cell lymphoma patients. Blood. 2013;122(14):2412-2424.
  7. Byrd JC, Brown JR, O'Brien S, et al. Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. N Engl J Med. 2014;371(3):213-223.
  8. O'Brien S, Jones JA, Coutre S, et al. Efficacy and safety of ibrutinib in patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic leukemia with 17p deletion from the phase II RESONATE-17 trial. 56th ASH Annual Meeting and Exposition; San Francisco, CA. Abstract 327.
  9. Hoellenriegel J, Meadows SA, Sivina M, et al. The phosphoinositide 3'-kinase delta inhibitor, CAL-101, inhibits B-cell receptor signaling and chemokine networks in chronic lymphocytic leukemia. Blood. 2011;118(13):3603-3612.
  10. Lannutti BJ, Meadows SA, Herman SE, et al. CAL-101, a p110delta selective phosphatidylinositol-3-kinase inhibitor for the treatment of B-cell malignancies, inhibits PI3K signaling and cellular viability. Blood. 2011;117(2):591-594.
  11. Furman RR, Sharman JP, Coutre SE, et al. Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. N Engl J Med. 2014;370(11):997-1007.
  12. Sharman JP, Coutre SE, Furman RR, et al. Second interim analysis of a phase 3 study of idelalisib (ZYDELIG) plus rituximab (R) for relapsed chronic lymphocytic leukemia (CLL): efficacy analysis of patient subpopulations with del(17p) and other adverse prognostic factors. 56th ASH Annual Meeting and Exposition; San Francisco, CA. Abstract 330.
  13. Zelenetz AD, Gordon LI, Wierda WG, et al. NCCN Clinical Practice Guidelines in Oncology. Non-Hodgkin Lymphoma. Version 2.2015. 2015. Available at:http://www.nccn.org/professionals/physician_gls/pdf/nhl.pdf. Accessed July 21, 2015.

Autoria e outros dados (tags, etc)

por cyto às 17:53

Domingo, 26.07.15

CLINICAL TRIALS LISTING GBM ABTA

 

  Page 1 of 44
 


Below is a list of the 439 clinical trials for Brain Tumor currently in our database.

Click Find a Match or call 1-877-769-4833 to see if these trials match your profile.

 
Title A Randomized Study of Nivolumab Versus Bevacizumab and a Safety Study of Nivolumab or Nivolumab Combined With Ipilimumab in Adult Subjects With Recurrent Glioblastoma (GBM) (CheckMate 143)  
Phase III  
Modality Immunotherapy (Monoclonal Antibody), Signal Transduction Inhibitor  
Sponsor Type Private
Title A Study Comparing Two Carboplatin Containing Regimens for Children and Young Adults With Previously Untreated Low Grade Glioma  
Phase III  
Modality Chemotherapy  
Sponsor Type Private
Title Armodafinil in Reducing Cancer-Related Fatigue in Patients With Glioblastoma Multiforme  
Phase III  
Modality Other  
Sponsor Type Government
Title Can Iron Lessen Anemia Due to Cancer and Chemotherapy: A Study to Investigate the Efficacy and Safety of Injectafer®  
Phase III  
Modality    
Sponsor Type Private
Title Extended Varenicline Treatment for Smoking Among Cancer Patients  
Phase III  
Modality Other, Supportive Care  
Sponsor Type Private
Title Fosaprepitant Dimeglumine in Preventing Chemotherapy-induced Nausea and Vomiting (MK-0517-031 AM3)  
Phase III  
Modality Hormonal Therapy, Supportive Care  
Sponsor Type Private
Title Long Term Chamomile Therapy for Anxiety  
Phase III  
Modality Supportive Care  
Sponsor Type Government
Title Maintenance Chemotherapy or Observation Following Induction Chemotherapy and Radiation Therapy in Treating Younger Patients With Newly Diagnosed Ependymoma  
Phase III  
Modality Chemotherapy, Radiation Therapy  
Sponsor Type Private
Title Placebo Controlled Double Blind Crossover Trial of Metformin for Brain Repair in Children With Cranial-Spinal Radiation for Medulloblastoma  
Phase III  
Modality Supportive Care  
Sponsor Type Private
Title Radiation Therapy With or Without Temozolomide in Treating Patients With Anaplastic Glioma  
Phase III  
Modality Chemotherapy, Radiation Therapy  
Sponsor Type Government

Autoria e outros dados (tags, etc)

por cyto às 18:26

Domingo, 26.07.15

Brain Tumor Treatments

 

Brain Tumor Treatments

 

Brain tumor treatment depends on a number of factors, including the type, location, size, and grade of the tumor, as well as the age and health of the patient. Your doctor can present your treatment options and tell you what to expect from each one.

 

Specialists who treat brain tumors include neurosurgeons, neurooncologists, medical oncologists, and radiation oncologists. In addition to the specialist, your treatment team may include other professionals such as a nurse, dietitian, mental health counselor, social worker, physical therapist, occupational therapist, and/or speech therapist.

 

Many people with brain tumors want to take an active part in making decisions about their medical care. They want to learn all they can about their disease and their treatment choices. Below are some questions you might want to ask your doctor:

  1. What type of brain tumor is it?
  2. Is it benign or malignant?
  3. What grade is my tumor?
  4. What are the treatment options? What do you recommend? Why?
  5. What are the benefits of each treatment option?
  6. What are the risks and possible side effects of each option?
  7. What is the treatment likely to cost?
  8. How will treatment affect my everyday activities?
  9. Should I participate in a clinical trial/research study? If so, which one?

It is not necessary to ask all of these questions or to understand the answers all at one time. There will be other opportunities to ask your doctor to explain things that are not clear and to ask for more information.

 

Before starting treatment, you may want a second opinion about your diagnosis and treatment plan. Some insurance companies require a second opinion; others may cover a second opinion if the patient or doctor requests it.

Autoria e outros dados (tags, etc)

por cyto às 18:23

Domingo, 26.07.15

Glioblastoma (GBM)

 

Glioblastoma (GBM)

 

Glioblastomas (GBM) are tumors that arise from astrocytes—the star-shaped cells that make up the “glue-like,” or supportive tissue of the brain. These tumors are usually highly malignant (cancerous) because the cells reproduce quickly and they are supported by a large network of blood vessels.

 

Location

Glioblastomas are generally found in the cerebral hemispheres of the brain, but can be found anywhere in the brain or spinal cord.

 

Description

Glioblastomas usually contain a mix of cell types. It is not unusual for these tumors to contain cystic mineral, calcium deposits, blood vessels, or a mixed grade of cells.

 

Glioblastomas are usually highly malignant—a large number of tumor cells are reproducing at any given time, and they are nourished by an ample blood supply. Dead cells may also be seen, especially toward the center of the tumor. Because these tumors come from normal brain cells, it is easy for them to invade and live within normal brain tissue. However, glioblastoma rarely spreads elsewhere in the body.

 

There are two types of glioblastomas:

  • Primary, or de novo: These tumors tend to form and make their presence known quickly. This is the most common form of glioblastoma; it is very aggressive.
  • Secondary: These tumors have a longer, somewhat slower growth history, but still are very aggressive. They may begin as lower-grade tumors which eventually become higher grade. They tend to be found in people 45 and younger, and represent about 10% of glioblastomas.

Symptoms

Because glioblastomas can grow rapidly, the most common symptoms are usually caused by increased pressure in the brain. These symptoms can include headache, nausea, vomiting, and drowsiness. Depending on the location of the tumor, patients can develop a variety of other symptoms such as weakness on one side of the body, memory and/or speech difficulties, and visual changes.

 

Incidence

This tumor represents about 15.4% of all primary brain tumors and about 60-75% of all astrocytomas. They increase in frequency with age, and affect more men than women. Only three percent of childhood brain tumors are glioblastomas.

 

Cause

Like many tumor types, the exact cause of glioblastoma is not known.

 

Treatment

Glioblastoma can be difficult to treat because the tumors contain so many different types of cells. Some cells may respond well to certain therapies, while others may not be affected at all. This is why the treatment plan for glioblastoma may combine several approaches.

 

The first step in treating glioblastoma is a procedure to make a diagnosis, relieve pressure on the brain, and safely remove as much tumor as possible through surgery. Because gliblastomas have finger-like tentacles, they are very difficult to completely remove. This is particularly true when they are growing near the parts of the brain that control important functions such as language and coordination.

 

Radiation and chemotherapy may be used to slow the growth of tumors that cannot be removed with surgery. Chemotherapy may also be used to delay the need for radiation in young children.

 

Learn more about different treatment options for brain tumors on our Treatment page.

 

Some glioblastoma treatments are available through research studies called clinical trials. Click here to access Trial ConnectTM, the ABTA's clinical trial matching service.

 

Prognosis

Prognosis is usually reported in years of "median survival." Median survival is the time at which an equal number of patients do better and an equal number of patients do worse. With standard treatment, median survival for adults with an anaplastic astrocytoma is about two to three years. For adults with more aggressive glioblastoma, treated with concurrent temozolamide and radiation therapy, median survival is about 14.6 months and two-year survival is 30%. However, a 2009 study reported that almost 10% of patients with glioblastoma may live five years or longer.

 

Children with high-grade tumors (grades III and IV) tend to do better than adults; five-year survival for children is about 25%.

 

In addition, glioblastoma patients who have had their MGMT gene shut off by a process called methylation also have prolonged survival rates. The MGMT gene is thought to be a significant predictor of response.

 

However, not all glioblastomas have the same biologic abnormalities. This may be the reason different patients respond differently to the same treatment and why different patients with the same tumor have different outcomes. Researchers continue to study the common characteristics of long-term brain tumor survivors, and how personalized and targeted treatments may be optimally used to treat brain tumor patients.

 

Emerging Biomarkers in Glioblastoma

There are a number of biomarkers, or molecular signatures, which have the potential to contribute to diagnosis, prognosis and prediction of response to therapy in glioblastoma. Click here to read more about emerging biomarkersand their impact on future therapies

Autoria e outros dados (tags, etc)

por cyto às 18:20

Pág. 1/6



Mais sobre mim

foto do autor


Subscrever por e-mail

A subscrição é anónima e gera, no máximo, um e-mail por dia.

Pesquisar

Pesquisar no Blog  

calendário

Julho 2015

D S T Q Q S S
1234
567891011
12131415161718
19202122232425
262728293031