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RT use on decline in early HL despite survival benefit
Credit: Rhoda Baer
SAN FRANCISCO—Results of a large study suggest that consolidation radiation therapy (RT) can improve survival in patients with stage I and II Hodgkin lymphoma (HL), but the use of RT in these patients may be on the decline.
In this study of more than 40,000 patients, the 10-year survival rate was 84% among those who received RT and 76% among those who did not.
Despite this benefit, the use of RT declined during the period studied, from 56% in 1998 to 41% in 2011.
These data were presented at the American Society for Radiation Oncology’s 56th Annual Meeting (abstract 1042).
“Multiple prospective, randomized trials have shown a significant improvement in disease control with the addition of RT,” said lead study author Rahul R. Parikh, MD, of the Mount Sinai Health System in New York.
“However, previous trials were limited by low patient numbers and limited follow-up and, thus, were unable to demonstrate an overall survival benefit. This is the largest dataset in this patient population to demonstrate a survival benefit with the addition of RT.”
Dr Parikh and his colleagues studied 41,502 patients who were diagnosed with stage I and II HL from 1998 to 2011. They were included in the National Cancer Data Base, which consists of cases from 1500 sites and represents more than 75% of all cancers diagnosed in the US.
The average patient age was 37 years (range, 18 to 90). The median follow-up was 7.5 years. Ninety-six percent of patients (n=39,842) received multi-agent chemotherapy, and 49% (n=20,441) received a median RT dose of 30.6 Gy.
The 10-year overall survival of the entire group was 80.8%. Patients receiving RT had significantly better overall survival than those who did not (84.4% vs 76.4%; P<0.00001).
When adjusting for age, stage, comorbidity, transplant, chemotherapy use, and socioeconomic status, RT use was still associated with significantly improved overall survival (hazard ratio=0.51; P<0.00001).
The study also showed that omitting RT was related to higher rates of salvage transplant procedures, a surrogate for persistent/relapsed disease (P=0.04).
Nevertheless, RT use decreased at the study sites from 56% to 41% between 1998 and 2011.
In 88.4% of patients who did not receive RT, the physician-reported reason was that RT was not part of the planned initial treatment strategy.
The research also indicated that RT use was more likely among younger patients (40 years or younger), those in a higher socioeconomic status, those who had access to health insurance, and those who received treatment at comprehensive cancer centers (all P<0.0001).
“[W]e have highlighted ongoing disparities in Hodgkin’s disease treatment, and it is important that we recognize these findings as potential barriers to care,” Dr Parikh said.
“Given the survival benefit demonstrated in this study, radiotherapy should be included in the combined modality approach of multi-agent chemotherapy followed by consolidation RT in order to maintain high overall survival rates for this curable disease.” 
Credit: Rhoda Baer
SAN FRANCISCO—Results of a large study suggest that consolidation radiation therapy (RT) can improve survival in patients with stage I and II Hodgkin lymphoma (HL), but the use of RT in these patients may be on the decline.
In this study of more than 40,000 patients, the 10-year survival rate was 84% among those who received RT and 76% among those who did not.
Despite this benefit, the use of RT declined during the period studied, from 56% in 1998 to 41% in 2011.
These data were presented at the American Society for Radiation Oncology’s 56th Annual Meeting (abstract 1042).
“Multiple prospective, randomized trials have shown a significant improvement in disease control with the addition of RT,” said lead study author Rahul R. Parikh, MD, of the Mount Sinai Health System in New York.
“However, previous trials were limited by low patient numbers and limited follow-up and, thus, were unable to demonstrate an overall survival benefit. This is the largest dataset in this patient population to demonstrate a survival benefit with the addition of RT.”
Dr Parikh and his colleagues studied 41,502 patients who were diagnosed with stage I and II HL from 1998 to 2011. They were included in the National Cancer Data Base, which consists of cases from 1500 sites and represents more than 75% of all cancers diagnosed in the US.
The average patient age was 37 years (range, 18 to 90). The median follow-up was 7.5 years. Ninety-six percent of patients (n=39,842) received multi-agent chemotherapy, and 49% (n=20,441) received a median RT dose of 30.6 Gy.
The 10-year overall survival of the entire group was 80.8%. Patients receiving RT had significantly better overall survival than those who did not (84.4% vs 76.4%; P<0.00001).
When adjusting for age, stage, comorbidity, transplant, chemotherapy use, and socioeconomic status, RT use was still associated with significantly improved overall survival (hazard ratio=0.51; P<0.00001).
The study also showed that omitting RT was related to higher rates of salvage transplant procedures, a surrogate for persistent/relapsed disease (P=0.04).
Nevertheless, RT use decreased at the study sites from 56% to 41% between 1998 and 2011.
In 88.4% of patients who did not receive RT, the physician-reported reason was that RT was not part of the planned initial treatment strategy.
The research also indicated that RT use was more likely among younger patients (40 years or younger), those in a higher socioeconomic status, those who had access to health insurance, and those who received treatment at comprehensive cancer centers (all P<0.0001).
“[W]e have highlighted ongoing disparities in Hodgkin’s disease treatment, and it is important that we recognize these findings as potential barriers to care,” Dr Parikh said.
“Given the survival benefit demonstrated in this study, radiotherapy should be included in the combined modality approach of multi-agent chemotherapy followed by consolidation RT in order to maintain high overall survival rates for this curable disease.”
Credit: Rhoda Baer
SAN FRANCISCO—Results of a large study suggest that consolidation radiation therapy (RT) can improve survival in patients with stage I and II Hodgkin lymphoma (HL), but the use of RT in these patients may be on the decline.
In this study of more than 40,000 patients, the 10-year survival rate was 84% among those who received RT and 76% among those who did not.
Despite this benefit, the use of RT declined during the period studied, from 56% in 1998 to 41% in 2011.
These data were presented at the American Society for Radiation Oncology’s 56th Annual Meeting (abstract 1042).
“Multiple prospective, randomized trials have shown a significant improvement in disease control with the addition of RT,” said lead study author Rahul R. Parikh, MD, of the Mount Sinai Health System in New York.
“However, previous trials were limited by low patient numbers and limited follow-up and, thus, were unable to demonstrate an overall survival benefit. This is the largest dataset in this patient population to demonstrate a survival benefit with the addition of RT.”
Dr Parikh and his colleagues studied 41,502 patients who were diagnosed with stage I and II HL from 1998 to 2011. They were included in the National Cancer Data Base, which consists of cases from 1500 sites and represents more than 75% of all cancers diagnosed in the US.
The average patient age was 37 years (range, 18 to 90). The median follow-up was 7.5 years. Ninety-six percent of patients (n=39,842) received multi-agent chemotherapy, and 49% (n=20,441) received a median RT dose of 30.6 Gy.
The 10-year overall survival of the entire group was 80.8%. Patients receiving RT had significantly better overall survival than those who did not (84.4% vs 76.4%; P<0.00001).
When adjusting for age, stage, comorbidity, transplant, chemotherapy use, and socioeconomic status, RT use was still associated with significantly improved overall survival (hazard ratio=0.51; P<0.00001).
The study also showed that omitting RT was related to higher rates of salvage transplant procedures, a surrogate for persistent/relapsed disease (P=0.04).
Nevertheless, RT use decreased at the study sites from 56% to 41% between 1998 and 2011.
In 88.4% of patients who did not receive RT, the physician-reported reason was that RT was not part of the planned initial treatment strategy.
The research also indicated that RT use was more likely among younger patients (40 years or younger), those in a higher socioeconomic status, those who had access to health insurance, and those who received treatment at comprehensive cancer centers (all P<0.0001).
“[W]e have highlighted ongoing disparities in Hodgkin’s disease treatment, and it is important that we recognize these findings as potential barriers to care,” Dr Parikh said.
“Given the survival benefit demonstrated in this study, radiotherapy should be included in the combined modality approach of multi-agent chemotherapy followed by consolidation RT in order to maintain high overall survival rates for this curable disease.”
Antifungal shows promise in hematologic conditions
WASHINGTON, DC—A new antifungal agent is as effective as an existing drug against invasive mold infection in patients with hematologic disorders, results of a phase 3 trial suggest.
Overall response and all-cause mortality rates were comparable with the newer drug, isavuconazole (ISA), and the existing drug, voriconazole (VRC).
The overall rates of treatment-emergent adverse events were comparable as well, but ISA was associated with a significantly lower incidence of several events.
Kieren Marr, MD, of Johns Hopkins University in Baltimore, Maryland, and her colleagues presented these results in a subset of patients from the SECURE trial at the 54th Interscience Conference on Antimicrobial Agents and Chemotherapy (poster M-1757).
Patient characteristics and safety outcomes
Of the 433 patients with a hematologic disorder enrolled in the trial, 217 had proven or probable invasive mold infection. The researchers divided patients into 2 groups according to disease: those with acute myeloid leukemia (AML) and those with acute lymphoblastic leukemia (ALL) or other conditions.
In all, 102 patients had AML, and 115 had ALL (n=28) or other conditions, including non-Hodgkin lymphoma (n=19), chronic lymphocytic leukemia (n=15), refractory anemia with excess blasts (n=9), myelodysplastic syndrome (n=8), chronic myeloid leukemia (n=6), and “other” underlying conditions (n=30).
Patients were randomized to receive VRC (n=105) or ISA (N=112). Thirty patients in the ISA arm and 26 in the VRC arm had undergone allogeneic transplant prior to therapy.
The primary outcome was all-cause mortality at day 42. Overall response and safety were secondary endpoints.
The overall rates of treatment-emergent adverse events were similar between ISA and VRC arms. Ninety-seven percent of patients in the ISA arm and 98% of patients in the VRC arm reported at least 1 treatment-emergent adverse event.
However, patients in the ISA arm had significantly fewer (P<0.05) events for the cardiac disorders, eye, psychiatric disorders, renal and urinary, and vascular system organ classes.
Response and mortality
All-cause mortality rates were comparable between the ISA and VRC arms—22% and 24%, respectively—as were overall response rates—39% and 34%, respectively—and complete response rates—13% and 10%, respectively.
All-cause mortality rates among patients with AML were 18% in the ISA arm and 15% in the VRC arm. Overall response rates were 36% and 48%, respectively.
For patients with ALL or other hematologic conditions, all-cause mortality rates were 26% in the ISA arm and 32% in the VRC arm. Overall response rates were 42% and 21%, respectively.
In transplant patients, the all-cause mortality rate was 27% for both the ISA and VRC arms. The overall response rate was 27% for both arms as well.
“These results show the potential of isavuconazole as a potent antifungal in the fight against invasive mold disease,” Dr Marr said.
ISA is an investigational antifungal under development by Astellas and Basilea Pharmaceutica International Ltd. The SECURE trial was funded by Astellas.
The US Food and Drug Administration recently accepted a new drug application seeking approval for ISA for the treatment of invasive aspergillosis and invasive mucormycosis.
WASHINGTON, DC—A new antifungal agent is as effective as an existing drug against invasive mold infection in patients with hematologic disorders, results of a phase 3 trial suggest.
Overall response and all-cause mortality rates were comparable with the newer drug, isavuconazole (ISA), and the existing drug, voriconazole (VRC).
The overall rates of treatment-emergent adverse events were comparable as well, but ISA was associated with a significantly lower incidence of several events.
Kieren Marr, MD, of Johns Hopkins University in Baltimore, Maryland, and her colleagues presented these results in a subset of patients from the SECURE trial at the 54th Interscience Conference on Antimicrobial Agents and Chemotherapy (poster M-1757).
Patient characteristics and safety outcomes
Of the 433 patients with a hematologic disorder enrolled in the trial, 217 had proven or probable invasive mold infection. The researchers divided patients into 2 groups according to disease: those with acute myeloid leukemia (AML) and those with acute lymphoblastic leukemia (ALL) or other conditions.
In all, 102 patients had AML, and 115 had ALL (n=28) or other conditions, including non-Hodgkin lymphoma (n=19), chronic lymphocytic leukemia (n=15), refractory anemia with excess blasts (n=9), myelodysplastic syndrome (n=8), chronic myeloid leukemia (n=6), and “other” underlying conditions (n=30).
Patients were randomized to receive VRC (n=105) or ISA (N=112). Thirty patients in the ISA arm and 26 in the VRC arm had undergone allogeneic transplant prior to therapy.
The primary outcome was all-cause mortality at day 42. Overall response and safety were secondary endpoints.
The overall rates of treatment-emergent adverse events were similar between ISA and VRC arms. Ninety-seven percent of patients in the ISA arm and 98% of patients in the VRC arm reported at least 1 treatment-emergent adverse event.
However, patients in the ISA arm had significantly fewer (P<0.05) events for the cardiac disorders, eye, psychiatric disorders, renal and urinary, and vascular system organ classes.
Response and mortality
All-cause mortality rates were comparable between the ISA and VRC arms—22% and 24%, respectively—as were overall response rates—39% and 34%, respectively—and complete response rates—13% and 10%, respectively.
All-cause mortality rates among patients with AML were 18% in the ISA arm and 15% in the VRC arm. Overall response rates were 36% and 48%, respectively.
For patients with ALL or other hematologic conditions, all-cause mortality rates were 26% in the ISA arm and 32% in the VRC arm. Overall response rates were 42% and 21%, respectively.
In transplant patients, the all-cause mortality rate was 27% for both the ISA and VRC arms. The overall response rate was 27% for both arms as well.
“These results show the potential of isavuconazole as a potent antifungal in the fight against invasive mold disease,” Dr Marr said.
ISA is an investigational antifungal under development by Astellas and Basilea Pharmaceutica International Ltd. The SECURE trial was funded by Astellas.
The US Food and Drug Administration recently accepted a new drug application seeking approval for ISA for the treatment of invasive aspergillosis and invasive mucormycosis.
WASHINGTON, DC—A new antifungal agent is as effective as an existing drug against invasive mold infection in patients with hematologic disorders, results of a phase 3 trial suggest.
Overall response and all-cause mortality rates were comparable with the newer drug, isavuconazole (ISA), and the existing drug, voriconazole (VRC).
The overall rates of treatment-emergent adverse events were comparable as well, but ISA was associated with a significantly lower incidence of several events.
Kieren Marr, MD, of Johns Hopkins University in Baltimore, Maryland, and her colleagues presented these results in a subset of patients from the SECURE trial at the 54th Interscience Conference on Antimicrobial Agents and Chemotherapy (poster M-1757).
Patient characteristics and safety outcomes
Of the 433 patients with a hematologic disorder enrolled in the trial, 217 had proven or probable invasive mold infection. The researchers divided patients into 2 groups according to disease: those with acute myeloid leukemia (AML) and those with acute lymphoblastic leukemia (ALL) or other conditions.
In all, 102 patients had AML, and 115 had ALL (n=28) or other conditions, including non-Hodgkin lymphoma (n=19), chronic lymphocytic leukemia (n=15), refractory anemia with excess blasts (n=9), myelodysplastic syndrome (n=8), chronic myeloid leukemia (n=6), and “other” underlying conditions (n=30).
Patients were randomized to receive VRC (n=105) or ISA (N=112). Thirty patients in the ISA arm and 26 in the VRC arm had undergone allogeneic transplant prior to therapy.
The primary outcome was all-cause mortality at day 42. Overall response and safety were secondary endpoints.
The overall rates of treatment-emergent adverse events were similar between ISA and VRC arms. Ninety-seven percent of patients in the ISA arm and 98% of patients in the VRC arm reported at least 1 treatment-emergent adverse event.
However, patients in the ISA arm had significantly fewer (P<0.05) events for the cardiac disorders, eye, psychiatric disorders, renal and urinary, and vascular system organ classes.
Response and mortality
All-cause mortality rates were comparable between the ISA and VRC arms—22% and 24%, respectively—as were overall response rates—39% and 34%, respectively—and complete response rates—13% and 10%, respectively.
All-cause mortality rates among patients with AML were 18% in the ISA arm and 15% in the VRC arm. Overall response rates were 36% and 48%, respectively.
For patients with ALL or other hematologic conditions, all-cause mortality rates were 26% in the ISA arm and 32% in the VRC arm. Overall response rates were 42% and 21%, respectively.
In transplant patients, the all-cause mortality rate was 27% for both the ISA and VRC arms. The overall response rate was 27% for both arms as well.
“These results show the potential of isavuconazole as a potent antifungal in the fight against invasive mold disease,” Dr Marr said.
ISA is an investigational antifungal under development by Astellas and Basilea Pharmaceutica International Ltd. The SECURE trial was funded by Astellas.
The US Food and Drug Administration recently accepted a new drug application seeking approval for ISA for the treatment of invasive aspergillosis and invasive mucormycosis.
Mutations linked to population disparities in cancers
Credit: NIGMS
Researchers have identified mutations in microRNAs (miRNAs) that are closely associated with certain global populations and have been implicated in cancers.
The group discovered 31 miRNAs containing variants that occur with different frequencies in African and non-African populations.
Seven of these miRNAs have been linked to the onset, progression, and spread of cancers with known health disparities between patients of European and African descent.
And a variant in one of these miRNAs is associated with a significantly increased risk of non-Hodgkin lymphoma (NHL).
These findings appear in BMC Medical Genomics.
To better understand miRNA diversity across the world, the researchers searched for miRNA variants in the genome sequences of 69 individuals from 14 populations in Europe, Asia, the Americas, and Africa. The samples included genetic material from diverse African populations, including 3 hunter-gatherer populations.
“We wanted to try to see if there was variability in miRNA that hadn’t been identified before,” said study author Renata A. Rawlings-Goss, PhD, of the University of Pennsylvania’s Perelman School of Medicine in Philadelphia.
Overall, the researchers found that miRNA sequences were similar across the populations they sampled. But they did identify 33 novel variants and found that variants in 31 miRNAs were population-differentiated.
The team searched available databases to see which genes these miRNAs were known to inhibit. Their query turned up a large proportion of genes involved in glucose and insulin metabolism, indicating a possible connection between diabetes risk and possessing one of these variants. The search also pointed to effects on genes implicated in cancers.
Specifically, 7 of the population-differentiated miRNAs are currently implicated as cancer biomarkers: hsa-mir-202, hsa-mir-423, hsa-mir-196a-2, hsa-mir-520h, hsa-mir-647, hsa-mir-943, and hsa-mir-1908.
Of particular interest was hsa-mir-202, which contained one of the most highly population-differentiated variants in the dataset and is under investigation as a marker for NHL and early stage breast cancer.
Recent research suggested that a T allele at SNP rs12355840 in hsa-mir-202 helps protect against death from breast cancer by increasing mature hsa-mir-202 expression levels, which leads to downregulation of its gene targets.
On the other hand, diminished expression of mature hsa-mir-202 in subjects harboring at least 1 non-T allele resulted in a significantly elevated risk of NHL (odds ratio=1.83, P=0.008).
Dr Rawlings-Goss and her colleagues found that African/African-American populations had a lower frequency of the T allele compared to European/Asian populations—26% vs 65%, on average. And this suggests decreased baseline expression levels of mature hsa-mir-202 in African populations.
“It’s becoming more and more apparent that miRNAs can have a broad-reaching and global effect on our health and adaptation to disease,” Dr Rawlings-Goss said. “Learning more about differences across populations could be helpful to doing early diagnostics and treating disease across diverse populations.”
Credit: NIGMS
Researchers have identified mutations in microRNAs (miRNAs) that are closely associated with certain global populations and have been implicated in cancers.
The group discovered 31 miRNAs containing variants that occur with different frequencies in African and non-African populations.
Seven of these miRNAs have been linked to the onset, progression, and spread of cancers with known health disparities between patients of European and African descent.
And a variant in one of these miRNAs is associated with a significantly increased risk of non-Hodgkin lymphoma (NHL).
These findings appear in BMC Medical Genomics.
To better understand miRNA diversity across the world, the researchers searched for miRNA variants in the genome sequences of 69 individuals from 14 populations in Europe, Asia, the Americas, and Africa. The samples included genetic material from diverse African populations, including 3 hunter-gatherer populations.
“We wanted to try to see if there was variability in miRNA that hadn’t been identified before,” said study author Renata A. Rawlings-Goss, PhD, of the University of Pennsylvania’s Perelman School of Medicine in Philadelphia.
Overall, the researchers found that miRNA sequences were similar across the populations they sampled. But they did identify 33 novel variants and found that variants in 31 miRNAs were population-differentiated.
The team searched available databases to see which genes these miRNAs were known to inhibit. Their query turned up a large proportion of genes involved in glucose and insulin metabolism, indicating a possible connection between diabetes risk and possessing one of these variants. The search also pointed to effects on genes implicated in cancers.
Specifically, 7 of the population-differentiated miRNAs are currently implicated as cancer biomarkers: hsa-mir-202, hsa-mir-423, hsa-mir-196a-2, hsa-mir-520h, hsa-mir-647, hsa-mir-943, and hsa-mir-1908.
Of particular interest was hsa-mir-202, which contained one of the most highly population-differentiated variants in the dataset and is under investigation as a marker for NHL and early stage breast cancer.
Recent research suggested that a T allele at SNP rs12355840 in hsa-mir-202 helps protect against death from breast cancer by increasing mature hsa-mir-202 expression levels, which leads to downregulation of its gene targets.
On the other hand, diminished expression of mature hsa-mir-202 in subjects harboring at least 1 non-T allele resulted in a significantly elevated risk of NHL (odds ratio=1.83, P=0.008).
Dr Rawlings-Goss and her colleagues found that African/African-American populations had a lower frequency of the T allele compared to European/Asian populations—26% vs 65%, on average. And this suggests decreased baseline expression levels of mature hsa-mir-202 in African populations.
“It’s becoming more and more apparent that miRNAs can have a broad-reaching and global effect on our health and adaptation to disease,” Dr Rawlings-Goss said. “Learning more about differences across populations could be helpful to doing early diagnostics and treating disease across diverse populations.”
Credit: NIGMS
Researchers have identified mutations in microRNAs (miRNAs) that are closely associated with certain global populations and have been implicated in cancers.
The group discovered 31 miRNAs containing variants that occur with different frequencies in African and non-African populations.
Seven of these miRNAs have been linked to the onset, progression, and spread of cancers with known health disparities between patients of European and African descent.
And a variant in one of these miRNAs is associated with a significantly increased risk of non-Hodgkin lymphoma (NHL).
These findings appear in BMC Medical Genomics.
To better understand miRNA diversity across the world, the researchers searched for miRNA variants in the genome sequences of 69 individuals from 14 populations in Europe, Asia, the Americas, and Africa. The samples included genetic material from diverse African populations, including 3 hunter-gatherer populations.
“We wanted to try to see if there was variability in miRNA that hadn’t been identified before,” said study author Renata A. Rawlings-Goss, PhD, of the University of Pennsylvania’s Perelman School of Medicine in Philadelphia.
Overall, the researchers found that miRNA sequences were similar across the populations they sampled. But they did identify 33 novel variants and found that variants in 31 miRNAs were population-differentiated.
The team searched available databases to see which genes these miRNAs were known to inhibit. Their query turned up a large proportion of genes involved in glucose and insulin metabolism, indicating a possible connection between diabetes risk and possessing one of these variants. The search also pointed to effects on genes implicated in cancers.
Specifically, 7 of the population-differentiated miRNAs are currently implicated as cancer biomarkers: hsa-mir-202, hsa-mir-423, hsa-mir-196a-2, hsa-mir-520h, hsa-mir-647, hsa-mir-943, and hsa-mir-1908.
Of particular interest was hsa-mir-202, which contained one of the most highly population-differentiated variants in the dataset and is under investigation as a marker for NHL and early stage breast cancer.
Recent research suggested that a T allele at SNP rs12355840 in hsa-mir-202 helps protect against death from breast cancer by increasing mature hsa-mir-202 expression levels, which leads to downregulation of its gene targets.
On the other hand, diminished expression of mature hsa-mir-202 in subjects harboring at least 1 non-T allele resulted in a significantly elevated risk of NHL (odds ratio=1.83, P=0.008).
Dr Rawlings-Goss and her colleagues found that African/African-American populations had a lower frequency of the T allele compared to European/Asian populations—26% vs 65%, on average. And this suggests decreased baseline expression levels of mature hsa-mir-202 in African populations.
“It’s becoming more and more apparent that miRNAs can have a broad-reaching and global effect on our health and adaptation to disease,” Dr Rawlings-Goss said. “Learning more about differences across populations could be helpful to doing early diagnostics and treating disease across diverse populations.”
Discovery could lead to better proteasome inhibitors
showing multiple myeloma
A newly discovered mechanism has paved the way for the next generation of proteasome inhibitors, according to a paper published in Chemistry & Biology.
Investigators developed a series of molecules that employ this mechanism, inhibiting the proteasome in 2 ways.
They are now planning to synthesize related compounds that may offer improved proteasome inhibition, target cancer cells more selectivity, and eliminate the resistance problems that occur with current drugs.
The group’s research began with epoxyketone, a molecule isolated from a cyanobacterium called carmaphycin, whose reactive group is the same as that of the proteasome inhibitor carfilzomib.
“Epoxyketones are very potent, selective inhibitors of the proteasome because they interact with this enzyme in 2 stages—the first reversible, and the second irreversible,” noted study author Daniela Trivella, PhD, of the Brazilian Biosciences National Laboratory at the Brazilian Center for Research in Energy and Materials in Campinas.
To optimize epoxyketone’s effects and find new reactive groups, the investigators developed and tested a series of synthetic analogs with slight structural modifications.
One of the molecules had an enone as a reactive group and had characteristics of carmaphycin and another natural molecule called syringolin, which was isolated from plant pathogens.
By investigating the reaction mechanisms of the new molecule, called carmaphycin-syringolin enone, the team verified that the enone interacts with the proteasome in 2 stages, with the second stage being irreversible.
The investigators also observed that, in the case of the enone, the second reaction occurs more slowly, increasing the duration of the reversible phase of carmaphycin-syringolin enone inhibition.
“Because the irreversible inactivation of the proteasome has toxic effects, the best window of reversibility observed for the carmaphycin-syringolin enone will potentially reduce the toxicity of this new class of proteasome inhibitors,” Dr Trivella said. “The compound would therefore present a balance between selectivity and potency.”
Toxicity tests are still underway. But the investigators have already conducted studies to determine exactly how the interaction between the enzyme target and the carmaphycin-syringolin enone target occurs.
“We discovered that a chemical reaction called hydroamination occurs, which had never before [been] seen under physiological conditions,” Dr Trivella said.
“This type of reaction is frequently used by synthetic chemists in preparing substances, but, normally, it requires very specific temperature and pH conditions and the use of catalysts to occur. It has never been reported as a mechanism of enzyme inhibition.”
Inspired by this new mechanism for proteasome inhibition, the investigators plan to synthesize and test a new series of carmaphycin-syringolin enone analogs to determine their effects on the therapeutic window and assess whether they are also capable of reacting with proteasomes that are resistant to traditional inhibitors.
showing multiple myeloma
A newly discovered mechanism has paved the way for the next generation of proteasome inhibitors, according to a paper published in Chemistry & Biology.
Investigators developed a series of molecules that employ this mechanism, inhibiting the proteasome in 2 ways.
They are now planning to synthesize related compounds that may offer improved proteasome inhibition, target cancer cells more selectivity, and eliminate the resistance problems that occur with current drugs.
The group’s research began with epoxyketone, a molecule isolated from a cyanobacterium called carmaphycin, whose reactive group is the same as that of the proteasome inhibitor carfilzomib.
“Epoxyketones are very potent, selective inhibitors of the proteasome because they interact with this enzyme in 2 stages—the first reversible, and the second irreversible,” noted study author Daniela Trivella, PhD, of the Brazilian Biosciences National Laboratory at the Brazilian Center for Research in Energy and Materials in Campinas.
To optimize epoxyketone’s effects and find new reactive groups, the investigators developed and tested a series of synthetic analogs with slight structural modifications.
One of the molecules had an enone as a reactive group and had characteristics of carmaphycin and another natural molecule called syringolin, which was isolated from plant pathogens.
By investigating the reaction mechanisms of the new molecule, called carmaphycin-syringolin enone, the team verified that the enone interacts with the proteasome in 2 stages, with the second stage being irreversible.
The investigators also observed that, in the case of the enone, the second reaction occurs more slowly, increasing the duration of the reversible phase of carmaphycin-syringolin enone inhibition.
“Because the irreversible inactivation of the proteasome has toxic effects, the best window of reversibility observed for the carmaphycin-syringolin enone will potentially reduce the toxicity of this new class of proteasome inhibitors,” Dr Trivella said. “The compound would therefore present a balance between selectivity and potency.”
Toxicity tests are still underway. But the investigators have already conducted studies to determine exactly how the interaction between the enzyme target and the carmaphycin-syringolin enone target occurs.
“We discovered that a chemical reaction called hydroamination occurs, which had never before [been] seen under physiological conditions,” Dr Trivella said.
“This type of reaction is frequently used by synthetic chemists in preparing substances, but, normally, it requires very specific temperature and pH conditions and the use of catalysts to occur. It has never been reported as a mechanism of enzyme inhibition.”
Inspired by this new mechanism for proteasome inhibition, the investigators plan to synthesize and test a new series of carmaphycin-syringolin enone analogs to determine their effects on the therapeutic window and assess whether they are also capable of reacting with proteasomes that are resistant to traditional inhibitors.
showing multiple myeloma
A newly discovered mechanism has paved the way for the next generation of proteasome inhibitors, according to a paper published in Chemistry & Biology.
Investigators developed a series of molecules that employ this mechanism, inhibiting the proteasome in 2 ways.
They are now planning to synthesize related compounds that may offer improved proteasome inhibition, target cancer cells more selectivity, and eliminate the resistance problems that occur with current drugs.
The group’s research began with epoxyketone, a molecule isolated from a cyanobacterium called carmaphycin, whose reactive group is the same as that of the proteasome inhibitor carfilzomib.
“Epoxyketones are very potent, selective inhibitors of the proteasome because they interact with this enzyme in 2 stages—the first reversible, and the second irreversible,” noted study author Daniela Trivella, PhD, of the Brazilian Biosciences National Laboratory at the Brazilian Center for Research in Energy and Materials in Campinas.
To optimize epoxyketone’s effects and find new reactive groups, the investigators developed and tested a series of synthetic analogs with slight structural modifications.
One of the molecules had an enone as a reactive group and had characteristics of carmaphycin and another natural molecule called syringolin, which was isolated from plant pathogens.
By investigating the reaction mechanisms of the new molecule, called carmaphycin-syringolin enone, the team verified that the enone interacts with the proteasome in 2 stages, with the second stage being irreversible.
The investigators also observed that, in the case of the enone, the second reaction occurs more slowly, increasing the duration of the reversible phase of carmaphycin-syringolin enone inhibition.
“Because the irreversible inactivation of the proteasome has toxic effects, the best window of reversibility observed for the carmaphycin-syringolin enone will potentially reduce the toxicity of this new class of proteasome inhibitors,” Dr Trivella said. “The compound would therefore present a balance between selectivity and potency.”
Toxicity tests are still underway. But the investigators have already conducted studies to determine exactly how the interaction between the enzyme target and the carmaphycin-syringolin enone target occurs.
“We discovered that a chemical reaction called hydroamination occurs, which had never before [been] seen under physiological conditions,” Dr Trivella said.
“This type of reaction is frequently used by synthetic chemists in preparing substances, but, normally, it requires very specific temperature and pH conditions and the use of catalysts to occur. It has never been reported as a mechanism of enzyme inhibition.”
Inspired by this new mechanism for proteasome inhibition, the investigators plan to synthesize and test a new series of carmaphycin-syringolin enone analogs to determine their effects on the therapeutic window and assess whether they are also capable of reacting with proteasomes that are resistant to traditional inhibitors.
AVAHO 2014 Meeting: Lymphoma Mini-Symposium Preview
Federal Practitioner recently talked with Dr. Adrian Weistner and Dr. Mark Roschewski of the National Institutes of Health. Both doctors will be presenting during the September 12, 2014 Lymphoma Mini-Symposium and panel discussion that kicks off this weekend’s 2014 AVAHO Meeting in Portland, Oregon.
Federal Practitioner recently talked with Dr. Adrian Weistner and Dr. Mark Roschewski of the National Institutes of Health. Both doctors will be presenting during the September 12, 2014 Lymphoma Mini-Symposium and panel discussion that kicks off this weekend’s 2014 AVAHO Meeting in Portland, Oregon.
Federal Practitioner recently talked with Dr. Adrian Weistner and Dr. Mark Roschewski of the National Institutes of Health. Both doctors will be presenting during the September 12, 2014 Lymphoma Mini-Symposium and panel discussion that kicks off this weekend’s 2014 AVAHO Meeting in Portland, Oregon.
Cancer centers may not allow for dignified deaths
Credit: NCI and
Mathews Media Group
A new study suggests many patients in cancer centers do not experience a dignified death.
Study investigators surveyed physicians and nurses in 16 hospitals belonging to 10 cancer centers in Baden-Württemberg, Germany.
The results revealed a need for cancer centers to invest more in palliative care services, adequate rooms for dying patients, staff training in end-of-life care, and advance-care-planning standards.
Karin Jors, of the University Medical Center Freiburg, and her colleagues reported these findings in Cancer.
Previous research has shown that hospitals are often ill-prepared to provide care for dying patients.
To investigate whether the circumstances for dying on cancer center wards allow for a dignified death, Jors and her colleagues surveyed physicians and nurses in German cancer centers.
Among 1131 survey respondents, 57% believed that patients could die with dignity on their ward.
Half of the surveyed staff members indicated that they rarely have enough time to care for dying patients, and 55% found the rooms available for dying patients unsatisfactory.
Only 19% of respondents felt they had been well-prepared to care for dying patients, and only 6% of physicians felt that way.
On the other hand, physicians perceived the circumstances for dying patients much more positively than nurses, especially regarding communication and life-prolonging measures.
While 72% of physicians reported that patients can usually die a dignified death on their ward, only 52% of nurses shared this opinion.
Palliative care staff reported much better conditions for dying patients than staff from other wards, with 95% of palliative care staff indicating that patients die with dignity on their wards.
“In our aging society, it is predicted that the number of hospital deaths will continue to rise in the coming years, and many of these deaths will be attributable to cancer,” Jors said.
“For this reason, it is particularly important that cancer centers strive to create a comfortable, dignified experience for dying patients and their families. Above all, this requires that staff members are provided with the adequate resources to care for these patients.”
The investigators therefore encourage the integration of palliative care into standard oncology care, beginning as early as diagnosis. They also believe physicians and nurses would benefit from increased education and training in end-of-life care.
Credit: NCI and
Mathews Media Group
A new study suggests many patients in cancer centers do not experience a dignified death.
Study investigators surveyed physicians and nurses in 16 hospitals belonging to 10 cancer centers in Baden-Württemberg, Germany.
The results revealed a need for cancer centers to invest more in palliative care services, adequate rooms for dying patients, staff training in end-of-life care, and advance-care-planning standards.
Karin Jors, of the University Medical Center Freiburg, and her colleagues reported these findings in Cancer.
Previous research has shown that hospitals are often ill-prepared to provide care for dying patients.
To investigate whether the circumstances for dying on cancer center wards allow for a dignified death, Jors and her colleagues surveyed physicians and nurses in German cancer centers.
Among 1131 survey respondents, 57% believed that patients could die with dignity on their ward.
Half of the surveyed staff members indicated that they rarely have enough time to care for dying patients, and 55% found the rooms available for dying patients unsatisfactory.
Only 19% of respondents felt they had been well-prepared to care for dying patients, and only 6% of physicians felt that way.
On the other hand, physicians perceived the circumstances for dying patients much more positively than nurses, especially regarding communication and life-prolonging measures.
While 72% of physicians reported that patients can usually die a dignified death on their ward, only 52% of nurses shared this opinion.
Palliative care staff reported much better conditions for dying patients than staff from other wards, with 95% of palliative care staff indicating that patients die with dignity on their wards.
“In our aging society, it is predicted that the number of hospital deaths will continue to rise in the coming years, and many of these deaths will be attributable to cancer,” Jors said.
“For this reason, it is particularly important that cancer centers strive to create a comfortable, dignified experience for dying patients and their families. Above all, this requires that staff members are provided with the adequate resources to care for these patients.”
The investigators therefore encourage the integration of palliative care into standard oncology care, beginning as early as diagnosis. They also believe physicians and nurses would benefit from increased education and training in end-of-life care.
Credit: NCI and
Mathews Media Group
A new study suggests many patients in cancer centers do not experience a dignified death.
Study investigators surveyed physicians and nurses in 16 hospitals belonging to 10 cancer centers in Baden-Württemberg, Germany.
The results revealed a need for cancer centers to invest more in palliative care services, adequate rooms for dying patients, staff training in end-of-life care, and advance-care-planning standards.
Karin Jors, of the University Medical Center Freiburg, and her colleagues reported these findings in Cancer.
Previous research has shown that hospitals are often ill-prepared to provide care for dying patients.
To investigate whether the circumstances for dying on cancer center wards allow for a dignified death, Jors and her colleagues surveyed physicians and nurses in German cancer centers.
Among 1131 survey respondents, 57% believed that patients could die with dignity on their ward.
Half of the surveyed staff members indicated that they rarely have enough time to care for dying patients, and 55% found the rooms available for dying patients unsatisfactory.
Only 19% of respondents felt they had been well-prepared to care for dying patients, and only 6% of physicians felt that way.
On the other hand, physicians perceived the circumstances for dying patients much more positively than nurses, especially regarding communication and life-prolonging measures.
While 72% of physicians reported that patients can usually die a dignified death on their ward, only 52% of nurses shared this opinion.
Palliative care staff reported much better conditions for dying patients than staff from other wards, with 95% of palliative care staff indicating that patients die with dignity on their wards.
“In our aging society, it is predicted that the number of hospital deaths will continue to rise in the coming years, and many of these deaths will be attributable to cancer,” Jors said.
“For this reason, it is particularly important that cancer centers strive to create a comfortable, dignified experience for dying patients and their families. Above all, this requires that staff members are provided with the adequate resources to care for these patients.”
The investigators therefore encourage the integration of palliative care into standard oncology care, beginning as early as diagnosis. They also believe physicians and nurses would benefit from increased education and training in end-of-life care.
Drug shows early promise for hematologic malignancies
A drug that targets mitochondrial function is largely safe and can be active in heavily pretreated patients with hematologic malignancies, a phase 1 trial indicates.
The drug, CPI-613, prompted responses in only 4 of 21 evaluable patients. However, 2 of those responses lasted more than 2 years.
CPI-613 was generally well-tolerated and did not induce bone marrow suppression. Four patients experienced renal failure, but it was reversed in 3 of them.
These results appear in Clinical Cancer Research.
“This drug is selectively taken up by cancer cells and then shuts down the production of energy in the mitochondria,” said study author Timothy Pardee, MD, PhD, of the Comprehensive Cancer Center of Wake Forest University in Winston-Salem, North Carolina.
“This is the first drug to inhibit mitochondria in this way, and, if it proves effective in further clinical trials, it will open up a whole new approach to fighting cancer.”
Dr Pardee and his colleagues evaluated CPI-613 in 26 patients with relapsed or refractory hematologic malignancies—11 with acute myeloid leukemia, 6 with non-Hodgkin lymphoma, 4 with multiple myeloma, 4 with myelodysplastic syndrome (MDS), and 1 with Hodgkin lymphoma.
The median patient age was 65 years (range, 19-81), and the median number of prior therapies was 3 (range, 1-9).
Treatment dosing and toxicity
Patients received CPI-613 as a 2-hour infusion on days 1 and 4 for 3 weeks every 28 days.
When the infusion time was shortened to 1 hour, renal failure occurred in 2 patients. At 3780 mg/m2, there were 2 dose-limiting toxicities. There were no such toxicities at a dose of 2940 mg/m2 over 2 hours, so this was considered the maximum-tolerated dose.
The following grade 2 or higher toxicities were probably or definitely related to treatment: nausea (1 grade 2), vomiting (1 grade 3), diarrhea (3 grade 2), proteinuria (1 grade 2), renal failure (4 grade 3), hypotension (1 grade 2), hypocalcemia (1 grade 2), hypoalbuminemia (1 grade 2), and hyperkalemia (1 grade 3).
Renal failure was resolved in 3 of the 4 patients. The remaining patient chose hospice care.
Response data
Five patients discontinued treatment—1 refused therapy, 1 acquired an infection, and 3 developed acute kidney failure.
Of the 21 patients evaluable for response, 4 had an objective response following CPI-613 treatment, and 2 had prolonged stable disease.
One patient with MDS achieved a complete response that has been maintained for more than 3 years. A patient with acute myeloid leukemia achieved a morphologically leukemia-free state, went on to transplant, and is still alive and leukemia-free.
A patient with Burkitt lymphoma achieved a partial response after 3 cycles of therapy that was maintained for 17 cycles. She discontinued CPI-613 to have her residual disease resected, and has not received any treatment since. She is now disease-free more than 12 months later.
A patient with cutaneous T-cell lymphoma achieved a partial response that has been sustained for more than 2 years. At her request, she started to receive continuous therapy (no 1-week rest period), and she remains on treatment without significant toxicities and no evidence of marrow suppression.
The 2 patients with prolonged stable disease had MDS. Their disease was stable for 8 and 12 cycles, respectively. Two patients with multiple myeloma also initially had stable disease, but they progressed after 2 and 4 cycles, respectively.
Two patients died from disease progression while on study.
The researchers said these results suggest that agents targeting mitochondrial metabolism can be safe and active in hematologic malignancies. A phase 2 trial of CPI-613 is now underway.
Support for the phase 1 trial was provided by National Cancer Institute grants P30CA012197 and 1K08CA169809, the Doug Coley Foundation for Leukemia Research, the Frances P. Tutwiler Fund, The MacKay Foundation for Cancer Research, and Cornerstone Pharmaceuticals, which manufactured and provided CPI-613.
A drug that targets mitochondrial function is largely safe and can be active in heavily pretreated patients with hematologic malignancies, a phase 1 trial indicates.
The drug, CPI-613, prompted responses in only 4 of 21 evaluable patients. However, 2 of those responses lasted more than 2 years.
CPI-613 was generally well-tolerated and did not induce bone marrow suppression. Four patients experienced renal failure, but it was reversed in 3 of them.
These results appear in Clinical Cancer Research.
“This drug is selectively taken up by cancer cells and then shuts down the production of energy in the mitochondria,” said study author Timothy Pardee, MD, PhD, of the Comprehensive Cancer Center of Wake Forest University in Winston-Salem, North Carolina.
“This is the first drug to inhibit mitochondria in this way, and, if it proves effective in further clinical trials, it will open up a whole new approach to fighting cancer.”
Dr Pardee and his colleagues evaluated CPI-613 in 26 patients with relapsed or refractory hematologic malignancies—11 with acute myeloid leukemia, 6 with non-Hodgkin lymphoma, 4 with multiple myeloma, 4 with myelodysplastic syndrome (MDS), and 1 with Hodgkin lymphoma.
The median patient age was 65 years (range, 19-81), and the median number of prior therapies was 3 (range, 1-9).
Treatment dosing and toxicity
Patients received CPI-613 as a 2-hour infusion on days 1 and 4 for 3 weeks every 28 days.
When the infusion time was shortened to 1 hour, renal failure occurred in 2 patients. At 3780 mg/m2, there were 2 dose-limiting toxicities. There were no such toxicities at a dose of 2940 mg/m2 over 2 hours, so this was considered the maximum-tolerated dose.
The following grade 2 or higher toxicities were probably or definitely related to treatment: nausea (1 grade 2), vomiting (1 grade 3), diarrhea (3 grade 2), proteinuria (1 grade 2), renal failure (4 grade 3), hypotension (1 grade 2), hypocalcemia (1 grade 2), hypoalbuminemia (1 grade 2), and hyperkalemia (1 grade 3).
Renal failure was resolved in 3 of the 4 patients. The remaining patient chose hospice care.
Response data
Five patients discontinued treatment—1 refused therapy, 1 acquired an infection, and 3 developed acute kidney failure.
Of the 21 patients evaluable for response, 4 had an objective response following CPI-613 treatment, and 2 had prolonged stable disease.
One patient with MDS achieved a complete response that has been maintained for more than 3 years. A patient with acute myeloid leukemia achieved a morphologically leukemia-free state, went on to transplant, and is still alive and leukemia-free.
A patient with Burkitt lymphoma achieved a partial response after 3 cycles of therapy that was maintained for 17 cycles. She discontinued CPI-613 to have her residual disease resected, and has not received any treatment since. She is now disease-free more than 12 months later.
A patient with cutaneous T-cell lymphoma achieved a partial response that has been sustained for more than 2 years. At her request, she started to receive continuous therapy (no 1-week rest period), and she remains on treatment without significant toxicities and no evidence of marrow suppression.
The 2 patients with prolonged stable disease had MDS. Their disease was stable for 8 and 12 cycles, respectively. Two patients with multiple myeloma also initially had stable disease, but they progressed after 2 and 4 cycles, respectively.
Two patients died from disease progression while on study.
The researchers said these results suggest that agents targeting mitochondrial metabolism can be safe and active in hematologic malignancies. A phase 2 trial of CPI-613 is now underway.
Support for the phase 1 trial was provided by National Cancer Institute grants P30CA012197 and 1K08CA169809, the Doug Coley Foundation for Leukemia Research, the Frances P. Tutwiler Fund, The MacKay Foundation for Cancer Research, and Cornerstone Pharmaceuticals, which manufactured and provided CPI-613.
A drug that targets mitochondrial function is largely safe and can be active in heavily pretreated patients with hematologic malignancies, a phase 1 trial indicates.
The drug, CPI-613, prompted responses in only 4 of 21 evaluable patients. However, 2 of those responses lasted more than 2 years.
CPI-613 was generally well-tolerated and did not induce bone marrow suppression. Four patients experienced renal failure, but it was reversed in 3 of them.
These results appear in Clinical Cancer Research.
“This drug is selectively taken up by cancer cells and then shuts down the production of energy in the mitochondria,” said study author Timothy Pardee, MD, PhD, of the Comprehensive Cancer Center of Wake Forest University in Winston-Salem, North Carolina.
“This is the first drug to inhibit mitochondria in this way, and, if it proves effective in further clinical trials, it will open up a whole new approach to fighting cancer.”
Dr Pardee and his colleagues evaluated CPI-613 in 26 patients with relapsed or refractory hematologic malignancies—11 with acute myeloid leukemia, 6 with non-Hodgkin lymphoma, 4 with multiple myeloma, 4 with myelodysplastic syndrome (MDS), and 1 with Hodgkin lymphoma.
The median patient age was 65 years (range, 19-81), and the median number of prior therapies was 3 (range, 1-9).
Treatment dosing and toxicity
Patients received CPI-613 as a 2-hour infusion on days 1 and 4 for 3 weeks every 28 days.
When the infusion time was shortened to 1 hour, renal failure occurred in 2 patients. At 3780 mg/m2, there were 2 dose-limiting toxicities. There were no such toxicities at a dose of 2940 mg/m2 over 2 hours, so this was considered the maximum-tolerated dose.
The following grade 2 or higher toxicities were probably or definitely related to treatment: nausea (1 grade 2), vomiting (1 grade 3), diarrhea (3 grade 2), proteinuria (1 grade 2), renal failure (4 grade 3), hypotension (1 grade 2), hypocalcemia (1 grade 2), hypoalbuminemia (1 grade 2), and hyperkalemia (1 grade 3).
Renal failure was resolved in 3 of the 4 patients. The remaining patient chose hospice care.
Response data
Five patients discontinued treatment—1 refused therapy, 1 acquired an infection, and 3 developed acute kidney failure.
Of the 21 patients evaluable for response, 4 had an objective response following CPI-613 treatment, and 2 had prolonged stable disease.
One patient with MDS achieved a complete response that has been maintained for more than 3 years. A patient with acute myeloid leukemia achieved a morphologically leukemia-free state, went on to transplant, and is still alive and leukemia-free.
A patient with Burkitt lymphoma achieved a partial response after 3 cycles of therapy that was maintained for 17 cycles. She discontinued CPI-613 to have her residual disease resected, and has not received any treatment since. She is now disease-free more than 12 months later.
A patient with cutaneous T-cell lymphoma achieved a partial response that has been sustained for more than 2 years. At her request, she started to receive continuous therapy (no 1-week rest period), and she remains on treatment without significant toxicities and no evidence of marrow suppression.
The 2 patients with prolonged stable disease had MDS. Their disease was stable for 8 and 12 cycles, respectively. Two patients with multiple myeloma also initially had stable disease, but they progressed after 2 and 4 cycles, respectively.
Two patients died from disease progression while on study.
The researchers said these results suggest that agents targeting mitochondrial metabolism can be safe and active in hematologic malignancies. A phase 2 trial of CPI-613 is now underway.
Support for the phase 1 trial was provided by National Cancer Institute grants P30CA012197 and 1K08CA169809, the Doug Coley Foundation for Leukemia Research, the Frances P. Tutwiler Fund, The MacKay Foundation for Cancer Research, and Cornerstone Pharmaceuticals, which manufactured and provided CPI-613.
Deaths from childhood cancer on decline in UK
Credit: Logan Tuttle
The rate of children dying from cancer in the UK has dropped 22% in the last decade, according to new figures published by Cancer Research UK.
From 2001 to 2003, 328 children died from cancer each year. But from 2010 to 2012, the annual death toll from childhood cancers decreased to 258.
The steepest decline in mortality was among leukemia patients. Death rates across all forms of leukemia combined dropped by 47%, from 102 to 53 deaths each year.
For acute lymphoblastic leukemia, the annual mortality rate decreased by 52%, falling from 63 to 29 deaths per year. For acute myeloid leukemia, the death rate fell by 33%, from 30 to 20 deaths per year. And for chronic myeloid leukemia, the death rate decreased by 74%, from 2 deaths per year to 1.
Annual mortality rates decreased for lymphoma patients as well. For all lymphomas, the death rate decreased by 31%, falling from 15 to 11 deaths per year. And for non-Hodgkin lymphomas, the rate dropped 35%, from 14 to 10 deaths per year.
Much of this success is due to new combinations of chemotherapy drugs, but efforts to improve imaging and radiotherapy techniques has also played a part, according to Cancer Research UK.
“It’s very encouraging to see that fewer children are dying of cancer, but a lot more needs to be done,” said Pam Kearns, director of the Cancer Research UK Clinical Trials Unit in Birmingham.
“Many children who survive cancer will live with the long-term side effects of their treatment that can have an impact throughout their adult lives, so it’s vital that we find kinder and even more effective treatments for them.”
Around 1600 children are diagnosed with cancer every year in the UK. Overall survival for childhood cancer has tripled since the 1960s. The proportion of children surviving their cancer for at least 10 years increased from 24% in 1966-1970 to 76% in 2001-2005.
Note: The above figures are age-standardized mortality rates, which take the age and size of the population into account, providing a figure for the number of children who die from cancer per million individuals. Looking at the numbers of children dying from the disease does not adjust for the increasing size of the UK population over the last 10 years, so changes in the numbers of deaths will not match the changes in rates.
Credit: Logan Tuttle
The rate of children dying from cancer in the UK has dropped 22% in the last decade, according to new figures published by Cancer Research UK.
From 2001 to 2003, 328 children died from cancer each year. But from 2010 to 2012, the annual death toll from childhood cancers decreased to 258.
The steepest decline in mortality was among leukemia patients. Death rates across all forms of leukemia combined dropped by 47%, from 102 to 53 deaths each year.
For acute lymphoblastic leukemia, the annual mortality rate decreased by 52%, falling from 63 to 29 deaths per year. For acute myeloid leukemia, the death rate fell by 33%, from 30 to 20 deaths per year. And for chronic myeloid leukemia, the death rate decreased by 74%, from 2 deaths per year to 1.
Annual mortality rates decreased for lymphoma patients as well. For all lymphomas, the death rate decreased by 31%, falling from 15 to 11 deaths per year. And for non-Hodgkin lymphomas, the rate dropped 35%, from 14 to 10 deaths per year.
Much of this success is due to new combinations of chemotherapy drugs, but efforts to improve imaging and radiotherapy techniques has also played a part, according to Cancer Research UK.
“It’s very encouraging to see that fewer children are dying of cancer, but a lot more needs to be done,” said Pam Kearns, director of the Cancer Research UK Clinical Trials Unit in Birmingham.
“Many children who survive cancer will live with the long-term side effects of their treatment that can have an impact throughout their adult lives, so it’s vital that we find kinder and even more effective treatments for them.”
Around 1600 children are diagnosed with cancer every year in the UK. Overall survival for childhood cancer has tripled since the 1960s. The proportion of children surviving their cancer for at least 10 years increased from 24% in 1966-1970 to 76% in 2001-2005.
Note: The above figures are age-standardized mortality rates, which take the age and size of the population into account, providing a figure for the number of children who die from cancer per million individuals. Looking at the numbers of children dying from the disease does not adjust for the increasing size of the UK population over the last 10 years, so changes in the numbers of deaths will not match the changes in rates.
Credit: Logan Tuttle
The rate of children dying from cancer in the UK has dropped 22% in the last decade, according to new figures published by Cancer Research UK.
From 2001 to 2003, 328 children died from cancer each year. But from 2010 to 2012, the annual death toll from childhood cancers decreased to 258.
The steepest decline in mortality was among leukemia patients. Death rates across all forms of leukemia combined dropped by 47%, from 102 to 53 deaths each year.
For acute lymphoblastic leukemia, the annual mortality rate decreased by 52%, falling from 63 to 29 deaths per year. For acute myeloid leukemia, the death rate fell by 33%, from 30 to 20 deaths per year. And for chronic myeloid leukemia, the death rate decreased by 74%, from 2 deaths per year to 1.
Annual mortality rates decreased for lymphoma patients as well. For all lymphomas, the death rate decreased by 31%, falling from 15 to 11 deaths per year. And for non-Hodgkin lymphomas, the rate dropped 35%, from 14 to 10 deaths per year.
Much of this success is due to new combinations of chemotherapy drugs, but efforts to improve imaging and radiotherapy techniques has also played a part, according to Cancer Research UK.
“It’s very encouraging to see that fewer children are dying of cancer, but a lot more needs to be done,” said Pam Kearns, director of the Cancer Research UK Clinical Trials Unit in Birmingham.
“Many children who survive cancer will live with the long-term side effects of their treatment that can have an impact throughout their adult lives, so it’s vital that we find kinder and even more effective treatments for them.”
Around 1600 children are diagnosed with cancer every year in the UK. Overall survival for childhood cancer has tripled since the 1960s. The proportion of children surviving their cancer for at least 10 years increased from 24% in 1966-1970 to 76% in 2001-2005.
Note: The above figures are age-standardized mortality rates, which take the age and size of the population into account, providing a figure for the number of children who die from cancer per million individuals. Looking at the numbers of children dying from the disease does not adjust for the increasing size of the UK population over the last 10 years, so changes in the numbers of deaths will not match the changes in rates.
Treatment Failure Patterns in Patients With Chronic Lymphocytic Leukemia: Results of a Large U.S. Observational Study
Purpose: Treatment for patients with chronic lymphocytic leukemia (CLL) is often not curative. Therefore, patients with CLL eventually experience disease progression with limited therapeutic options, even if the duration of remission can be long. Median overall survival for patients with CLL is usually 8 to 12 years, but there is a large variation in survival among individual patients, ranging from several months to a normal life expectancy. This retrospective observational study describes course of treatment and occurrence of treatment failure in patients with CLL.
Methods: Adult patients with ≥ 1 diagnosis of CLL and ≥ 1 claim for a medication used to treat CLL were identified in the IMS PharMetrics Plus database (January 2008 to September 2013). Patients were excluded if they had evidence of a nonhematologic malignancy, used a non-CLL antineoplastic agent, or received a stem cell transplant during the 12-month baseline period. Initial therapy was defined as the single agent or the combination of medications used to treat CLL that was given to patients in the first 30 days following the first claim for a medication (index date) used to treat CLL. Treatment failure was identified based on earliest occurrence of one of the following events: initiation of a new treatment for CLL that was not part of the initial therapy, resumption of any CLL treatment following a minimum of 3-month break in treatment, radiotherapy, stem cell transplant, hospital mortality, or hospice care.
Results: A total of 6,015 patients with CLL were identified (mean patient aged 63 years; proportion female: 36%). Patients were observed for 22.7 months on average following treatment initiation. Median time between first CLL diagnosis and first claim for a medication used to treat CLL was 102 days. Mean Charlson comorbidity index was 3.2. More frequent comorbidities were hypertension (44%), anemias (37%), coagulation deficiency (21%), diabetes without chronic complications (18%), and chronic pulmonary disease (18%). Of the 6,015 patients with CLL, 2,734 (45%) experienced treatment failure. Main observed measures for treatment failure were initiation of a new CLL treatment that was not part of the initial therapy (41%; mean time to treatment failure [TTF]: 286 days), resumption of any CLL treatment (39%; TTF: 346 days), radiotherapy (14%; TTF: 199 days), and stem cell transplant (5%; TTF: 116 days). Very few patients experienced treatment failure observed through hospice care (0.4%; TTF: 387 days).
Conclusions: A notable number (45%) of patients with CLL experienced treatment failure, which was mainly observed through initiation of alternative therapies or the need for a holiday after initial therapy. These data help in our understanding of CLL treatment failure patterns, which is a first step toward reducing the burden of disease in patients with CLL. Further research evaluating the reasons and economic implications of treatment failure is warranted.
Purpose: Treatment for patients with chronic lymphocytic leukemia (CLL) is often not curative. Therefore, patients with CLL eventually experience disease progression with limited therapeutic options, even if the duration of remission can be long. Median overall survival for patients with CLL is usually 8 to 12 years, but there is a large variation in survival among individual patients, ranging from several months to a normal life expectancy. This retrospective observational study describes course of treatment and occurrence of treatment failure in patients with CLL.
Methods: Adult patients with ≥ 1 diagnosis of CLL and ≥ 1 claim for a medication used to treat CLL were identified in the IMS PharMetrics Plus database (January 2008 to September 2013). Patients were excluded if they had evidence of a nonhematologic malignancy, used a non-CLL antineoplastic agent, or received a stem cell transplant during the 12-month baseline period. Initial therapy was defined as the single agent or the combination of medications used to treat CLL that was given to patients in the first 30 days following the first claim for a medication (index date) used to treat CLL. Treatment failure was identified based on earliest occurrence of one of the following events: initiation of a new treatment for CLL that was not part of the initial therapy, resumption of any CLL treatment following a minimum of 3-month break in treatment, radiotherapy, stem cell transplant, hospital mortality, or hospice care.
Results: A total of 6,015 patients with CLL were identified (mean patient aged 63 years; proportion female: 36%). Patients were observed for 22.7 months on average following treatment initiation. Median time between first CLL diagnosis and first claim for a medication used to treat CLL was 102 days. Mean Charlson comorbidity index was 3.2. More frequent comorbidities were hypertension (44%), anemias (37%), coagulation deficiency (21%), diabetes without chronic complications (18%), and chronic pulmonary disease (18%). Of the 6,015 patients with CLL, 2,734 (45%) experienced treatment failure. Main observed measures for treatment failure were initiation of a new CLL treatment that was not part of the initial therapy (41%; mean time to treatment failure [TTF]: 286 days), resumption of any CLL treatment (39%; TTF: 346 days), radiotherapy (14%; TTF: 199 days), and stem cell transplant (5%; TTF: 116 days). Very few patients experienced treatment failure observed through hospice care (0.4%; TTF: 387 days).
Conclusions: A notable number (45%) of patients with CLL experienced treatment failure, which was mainly observed through initiation of alternative therapies or the need for a holiday after initial therapy. These data help in our understanding of CLL treatment failure patterns, which is a first step toward reducing the burden of disease in patients with CLL. Further research evaluating the reasons and economic implications of treatment failure is warranted.
Purpose: Treatment for patients with chronic lymphocytic leukemia (CLL) is often not curative. Therefore, patients with CLL eventually experience disease progression with limited therapeutic options, even if the duration of remission can be long. Median overall survival for patients with CLL is usually 8 to 12 years, but there is a large variation in survival among individual patients, ranging from several months to a normal life expectancy. This retrospective observational study describes course of treatment and occurrence of treatment failure in patients with CLL.
Methods: Adult patients with ≥ 1 diagnosis of CLL and ≥ 1 claim for a medication used to treat CLL were identified in the IMS PharMetrics Plus database (January 2008 to September 2013). Patients were excluded if they had evidence of a nonhematologic malignancy, used a non-CLL antineoplastic agent, or received a stem cell transplant during the 12-month baseline period. Initial therapy was defined as the single agent or the combination of medications used to treat CLL that was given to patients in the first 30 days following the first claim for a medication (index date) used to treat CLL. Treatment failure was identified based on earliest occurrence of one of the following events: initiation of a new treatment for CLL that was not part of the initial therapy, resumption of any CLL treatment following a minimum of 3-month break in treatment, radiotherapy, stem cell transplant, hospital mortality, or hospice care.
Results: A total of 6,015 patients with CLL were identified (mean patient aged 63 years; proportion female: 36%). Patients were observed for 22.7 months on average following treatment initiation. Median time between first CLL diagnosis and first claim for a medication used to treat CLL was 102 days. Mean Charlson comorbidity index was 3.2. More frequent comorbidities were hypertension (44%), anemias (37%), coagulation deficiency (21%), diabetes without chronic complications (18%), and chronic pulmonary disease (18%). Of the 6,015 patients with CLL, 2,734 (45%) experienced treatment failure. Main observed measures for treatment failure were initiation of a new CLL treatment that was not part of the initial therapy (41%; mean time to treatment failure [TTF]: 286 days), resumption of any CLL treatment (39%; TTF: 346 days), radiotherapy (14%; TTF: 199 days), and stem cell transplant (5%; TTF: 116 days). Very few patients experienced treatment failure observed through hospice care (0.4%; TTF: 387 days).
Conclusions: A notable number (45%) of patients with CLL experienced treatment failure, which was mainly observed through initiation of alternative therapies or the need for a holiday after initial therapy. These data help in our understanding of CLL treatment failure patterns, which is a first step toward reducing the burden of disease in patients with CLL. Further research evaluating the reasons and economic implications of treatment failure is warranted.
Association Between Rituximab Use and Progressive Multifocal Leukoencephalopathy Among Non-HIV Non-Hodgkin Lymphoma VA Patients
Purpose: Progressive multifocal leukoencephalopathy (PML) is a rare, fatal disease that results from activation of a highly prevalent, dormant John Cunningham (JC) virus—a variant of human polyomavirus—during immunosuppressed states. Rituximab, a CD20 monoclonal antibody immunomodulator, has been approved for non-Hodgkin lymphoma (NHL).
Methods: Using electronic medical records from the VA, ICD-9 codes were used to identify patients diagnosed with NHL, PML, and HIV within the VA from 2003 to 2011. Pharmacy records were used to identify patients receiving rituximab, cyclophosphamide, hydroxydaunorubicin, and vncristine. This project was conducted inside the Veterans Affairs Informatics and Computing Infrastructure after obtaining approvals from the VA IRB and other oversight groups.
Results: We identified 57,041 non-HIV NHL patients. A total of 14 out of 57,041 (0.025%) patients had developed PML; 7 out of 8,895 (7.8 per 10,000) were NHL patients who received rituximab subsequently developed PML; 7 out of 48,146 (1.5 per 10,000) were NHL patients who did not receive rituximab subsequently developed PML, which results in a statistically significant unadjusted relative risk of 5.4 (95% CI: 1.9 - 15.4) and an attributable risk of 6.3 per 10,000. Univariate analyses of other outcomes were not statistically significant between patients who received and those that did not receive rituximab.
Conclusions: These results show that among lymphoma patients, the use of rituximab is associated with a statistically significant relative risk for documented PML of 5.4. Measurement of JC virus prior to initiation of rituximab therapy as well as during rituximab therapy should be considered.
Purpose: Progressive multifocal leukoencephalopathy (PML) is a rare, fatal disease that results from activation of a highly prevalent, dormant John Cunningham (JC) virus—a variant of human polyomavirus—during immunosuppressed states. Rituximab, a CD20 monoclonal antibody immunomodulator, has been approved for non-Hodgkin lymphoma (NHL).
Methods: Using electronic medical records from the VA, ICD-9 codes were used to identify patients diagnosed with NHL, PML, and HIV within the VA from 2003 to 2011. Pharmacy records were used to identify patients receiving rituximab, cyclophosphamide, hydroxydaunorubicin, and vncristine. This project was conducted inside the Veterans Affairs Informatics and Computing Infrastructure after obtaining approvals from the VA IRB and other oversight groups.
Results: We identified 57,041 non-HIV NHL patients. A total of 14 out of 57,041 (0.025%) patients had developed PML; 7 out of 8,895 (7.8 per 10,000) were NHL patients who received rituximab subsequently developed PML; 7 out of 48,146 (1.5 per 10,000) were NHL patients who did not receive rituximab subsequently developed PML, which results in a statistically significant unadjusted relative risk of 5.4 (95% CI: 1.9 - 15.4) and an attributable risk of 6.3 per 10,000. Univariate analyses of other outcomes were not statistically significant between patients who received and those that did not receive rituximab.
Conclusions: These results show that among lymphoma patients, the use of rituximab is associated with a statistically significant relative risk for documented PML of 5.4. Measurement of JC virus prior to initiation of rituximab therapy as well as during rituximab therapy should be considered.
Purpose: Progressive multifocal leukoencephalopathy (PML) is a rare, fatal disease that results from activation of a highly prevalent, dormant John Cunningham (JC) virus—a variant of human polyomavirus—during immunosuppressed states. Rituximab, a CD20 monoclonal antibody immunomodulator, has been approved for non-Hodgkin lymphoma (NHL).
Methods: Using electronic medical records from the VA, ICD-9 codes were used to identify patients diagnosed with NHL, PML, and HIV within the VA from 2003 to 2011. Pharmacy records were used to identify patients receiving rituximab, cyclophosphamide, hydroxydaunorubicin, and vncristine. This project was conducted inside the Veterans Affairs Informatics and Computing Infrastructure after obtaining approvals from the VA IRB and other oversight groups.
Results: We identified 57,041 non-HIV NHL patients. A total of 14 out of 57,041 (0.025%) patients had developed PML; 7 out of 8,895 (7.8 per 10,000) were NHL patients who received rituximab subsequently developed PML; 7 out of 48,146 (1.5 per 10,000) were NHL patients who did not receive rituximab subsequently developed PML, which results in a statistically significant unadjusted relative risk of 5.4 (95% CI: 1.9 - 15.4) and an attributable risk of 6.3 per 10,000. Univariate analyses of other outcomes were not statistically significant between patients who received and those that did not receive rituximab.
Conclusions: These results show that among lymphoma patients, the use of rituximab is associated with a statistically significant relative risk for documented PML of 5.4. Measurement of JC virus prior to initiation of rituximab therapy as well as during rituximab therapy should be considered.