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SAN DIEGO – Adolescents and young adults with Hodgkin’s lymphoma can have high response rates and durable remissions under protocols developed for children, with potentially lower long-term toxicities than those commonly seen with adult-oriented regimens, said investigators at the annual meeting of the American Society of Hematology.
The 15- to 20-year-olds with Hodgkin’s lymphoma who were treated under two similar Children’s Oncology Group protocols had a 5-year event-free survival rate of 85.9%, compared with 87.0% for patients younger than 15 years. The 10-year rate was 77.3% in the older patients and 83.8% in the younger group (P = .515), reported Dr. Karen S. Fernandez of the pediatrics department at the University of Illinois, Peoria.
These 5-year event-free survival results are comparable to outcomes of other studies in which adolescents and young adults were treated with adult cooperative-group protocols. Moreover, the cumulative doses of alkylators, anthracyclines, and etoposide used are below thresholds usually associated with significant long-term toxicities, Dr. Fernandez noted.
"Based on this data, we favor the use of pediatric-focused therapy with dose-limited regimens for adolescents and young adults with Hodgkin’s lymphoma in whom decreasing long-term effects is important to improve quality of life, particularly for adolescents with advanced stages," she said.
There is no widely accepted standard of treatment for adolescents and young adults with Hodgkin’s lymphoma, in part because different centers variously treat teens with adult or pediatric protocols, and published data specifically regarding the treatment of adolescents and young adults with Hodgkin’s lymphoma are scarce, Dr. Fernandez said.
She and her colleagues in the Children’s Oncology Group tried to find a balance between maximum possible cure rates and reduced long-term effects by conducting a retrospective analysis comparing children younger than 15 years with adolescents and young adults aged 15-20 years, in the Children’s Oncology Group protocols P9425 and P9426.
The P9425 study looked at the ABVE-PC regimen (doxorubicin [Adriamycin], bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide in dose-dense application) in patients with advanced-stage Hodgkin’s lymphoma. P9426 evaluated the ABVE regimen (the same combination, also dose-dense but without prednisone or cyclophosphamide) in patients with low-stage Hodgkin’s lymphoma.
Patients with an early response in P9425 received 21 Gy of radiation after three cycles of ABVE-PC spaced 21 days apart; patients with a slow response received the same radiation dose after five cycles.
In the P9426 protocol, patients with early responses received 25 Gy after two cycles, while all others received the same radiation dose after four cycles of ABVE. Patients in both protocols received dexrazoxane at the investigators’ discretion.
The cumulative chemotherapy doses delivered in the ABVE and ABVE-PC regimens in these trials were significantly lower than those delivered in other trials of patients with standard or high- to intermediate-risk Hodgkin’s disease, including the BEACOPP regimen (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine [Oncovin], prednisone, and procarbazine), COPP-ABVD (the same drugs as BEACOPP plus vinblastine and dacarbazine), and ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine).
When Dr. Fernandez and her colleagues conducted a Cox regression analysis of patients in the combined studies, they found that neither sex, histologic subtypes, nor tumor staging was predictive of outcomes.
She noted that the study was limited by the retrospective design and the small number of adolescents in each group (104 in P9425 and 99 in P9426). Another limitation was the fact that neither study was designed to distinguish between children and adolescents/young adults, she said.
The investigators plan to collaborate with adult oncology groups to standardize treatment of adolescents and young adults, Dr. Fernandez concluded.
In the question and response session following the presentation, Dr. Jonathan Friedberg, chief of hematology/oncology at the University of Rochester (N.Y.), noted that the toxicities associated with therapy are not all drug related.
"Your pediatric group seems to be very focused on decreasing the doses of chemotherapy in an effort to mediate late toxicity, but I think most people would accept that radiation is probably the big driver of late toxicity, and it appears that in these regimens you’re giving radiation to patients with advanced-stage Hodgkin’s," commented Dr. Friedberg, who moderated the session but was not involved in the study.
Dr. Fernandez acknowledged that all patients in the P9425 and P9426 protocols received radiation, but added that the group is currently conducting trials in which radiation will be given based on patient responses determined by PET scans following the first cycle of chemotherapy.
The study was supported by the Children’s Oncology Group. Dr. Fernandez reported that she had no relevant conflicts of interest. Dr. Friedberg reported being a consultant to or receiving honoraria from Genentech, Astellas, Lilly, Trubion, Seattle Genetics, and Cephalon.
Adolescents
and young adults with Hodgkin’s lymphoma were treated on two Children’s
Oncology Group clinical trials that were designed to mitigate the late effects
of successful therapy by reducing the cumulative doses of alkylating agents,
anthracyclines, and etoposide. They experienced 5- and 10-year event-free
outcomes which were not statistically different than those experienced by
younger patients.
In most other cancers
in the pediatric age group, age at diagnosis has nearly always exerted
prognostic significance. Hodgkin’s has a peak incidence in adolescence and
young adulthood, and favorable histologic subtypes of the disease are known to
predominate in younger children. The importance of this report is that
excellent outcomes can be obtained in the older patients with a combination
chemotherapy regimen that uses lower cumulative doses of classes of drugs known
to be associated with significant potential for deleterious late effects. This
is, indeed, good news that overall drug doses can be safely reduced without
jeopardizing disease control; however, any long-term quality of life
differences between younger children and the adolescent and young adult
population as a result of reducing cumulative doses is not yet established.
Although dose
reduction of chemotherapy is one strategy to reduce the long-term and delayed
side effects of therapy for a highly curable disease, the reduction in exposure
to therapeutic irradiation or its elimination entirely remains an equally
important consideration for the optimal management of younger children as well
as adolescents and young adults with Hodgkin’s disease.
Dr. Gregory H. Reaman, an associate editor of The Oncology Report, is professor of
pediatrics at the George Washington University
School of Medicine and Health Sciences
and Children’s National Medical Center
in Washington.
Adolescents
and young adults with Hodgkin’s lymphoma were treated on two Children’s
Oncology Group clinical trials that were designed to mitigate the late effects
of successful therapy by reducing the cumulative doses of alkylating agents,
anthracyclines, and etoposide. They experienced 5- and 10-year event-free
outcomes which were not statistically different than those experienced by
younger patients.
In most other cancers
in the pediatric age group, age at diagnosis has nearly always exerted
prognostic significance. Hodgkin’s has a peak incidence in adolescence and
young adulthood, and favorable histologic subtypes of the disease are known to
predominate in younger children. The importance of this report is that
excellent outcomes can be obtained in the older patients with a combination
chemotherapy regimen that uses lower cumulative doses of classes of drugs known
to be associated with significant potential for deleterious late effects. This
is, indeed, good news that overall drug doses can be safely reduced without
jeopardizing disease control; however, any long-term quality of life
differences between younger children and the adolescent and young adult
population as a result of reducing cumulative doses is not yet established.
Although dose
reduction of chemotherapy is one strategy to reduce the long-term and delayed
side effects of therapy for a highly curable disease, the reduction in exposure
to therapeutic irradiation or its elimination entirely remains an equally
important consideration for the optimal management of younger children as well
as adolescents and young adults with Hodgkin’s disease.
Dr. Gregory H. Reaman, an associate editor of The Oncology Report, is professor of
pediatrics at the George Washington University
School of Medicine and Health Sciences
and Children’s National Medical Center
in Washington.
Adolescents
and young adults with Hodgkin’s lymphoma were treated on two Children’s
Oncology Group clinical trials that were designed to mitigate the late effects
of successful therapy by reducing the cumulative doses of alkylating agents,
anthracyclines, and etoposide. They experienced 5- and 10-year event-free
outcomes which were not statistically different than those experienced by
younger patients.
In most other cancers
in the pediatric age group, age at diagnosis has nearly always exerted
prognostic significance. Hodgkin’s has a peak incidence in adolescence and
young adulthood, and favorable histologic subtypes of the disease are known to
predominate in younger children. The importance of this report is that
excellent outcomes can be obtained in the older patients with a combination
chemotherapy regimen that uses lower cumulative doses of classes of drugs known
to be associated with significant potential for deleterious late effects. This
is, indeed, good news that overall drug doses can be safely reduced without
jeopardizing disease control; however, any long-term quality of life
differences between younger children and the adolescent and young adult
population as a result of reducing cumulative doses is not yet established.
Although dose
reduction of chemotherapy is one strategy to reduce the long-term and delayed
side effects of therapy for a highly curable disease, the reduction in exposure
to therapeutic irradiation or its elimination entirely remains an equally
important consideration for the optimal management of younger children as well
as adolescents and young adults with Hodgkin’s disease.
Dr. Gregory H. Reaman, an associate editor of The Oncology Report, is professor of
pediatrics at the George Washington University
School of Medicine and Health Sciences
and Children’s National Medical Center
in Washington.
SAN DIEGO – Adolescents and young adults with Hodgkin’s lymphoma can have high response rates and durable remissions under protocols developed for children, with potentially lower long-term toxicities than those commonly seen with adult-oriented regimens, said investigators at the annual meeting of the American Society of Hematology.
The 15- to 20-year-olds with Hodgkin’s lymphoma who were treated under two similar Children’s Oncology Group protocols had a 5-year event-free survival rate of 85.9%, compared with 87.0% for patients younger than 15 years. The 10-year rate was 77.3% in the older patients and 83.8% in the younger group (P = .515), reported Dr. Karen S. Fernandez of the pediatrics department at the University of Illinois, Peoria.
These 5-year event-free survival results are comparable to outcomes of other studies in which adolescents and young adults were treated with adult cooperative-group protocols. Moreover, the cumulative doses of alkylators, anthracyclines, and etoposide used are below thresholds usually associated with significant long-term toxicities, Dr. Fernandez noted.
"Based on this data, we favor the use of pediatric-focused therapy with dose-limited regimens for adolescents and young adults with Hodgkin’s lymphoma in whom decreasing long-term effects is important to improve quality of life, particularly for adolescents with advanced stages," she said.
There is no widely accepted standard of treatment for adolescents and young adults with Hodgkin’s lymphoma, in part because different centers variously treat teens with adult or pediatric protocols, and published data specifically regarding the treatment of adolescents and young adults with Hodgkin’s lymphoma are scarce, Dr. Fernandez said.
She and her colleagues in the Children’s Oncology Group tried to find a balance between maximum possible cure rates and reduced long-term effects by conducting a retrospective analysis comparing children younger than 15 years with adolescents and young adults aged 15-20 years, in the Children’s Oncology Group protocols P9425 and P9426.
The P9425 study looked at the ABVE-PC regimen (doxorubicin [Adriamycin], bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide in dose-dense application) in patients with advanced-stage Hodgkin’s lymphoma. P9426 evaluated the ABVE regimen (the same combination, also dose-dense but without prednisone or cyclophosphamide) in patients with low-stage Hodgkin’s lymphoma.
Patients with an early response in P9425 received 21 Gy of radiation after three cycles of ABVE-PC spaced 21 days apart; patients with a slow response received the same radiation dose after five cycles.
In the P9426 protocol, patients with early responses received 25 Gy after two cycles, while all others received the same radiation dose after four cycles of ABVE. Patients in both protocols received dexrazoxane at the investigators’ discretion.
The cumulative chemotherapy doses delivered in the ABVE and ABVE-PC regimens in these trials were significantly lower than those delivered in other trials of patients with standard or high- to intermediate-risk Hodgkin’s disease, including the BEACOPP regimen (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine [Oncovin], prednisone, and procarbazine), COPP-ABVD (the same drugs as BEACOPP plus vinblastine and dacarbazine), and ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine).
When Dr. Fernandez and her colleagues conducted a Cox regression analysis of patients in the combined studies, they found that neither sex, histologic subtypes, nor tumor staging was predictive of outcomes.
She noted that the study was limited by the retrospective design and the small number of adolescents in each group (104 in P9425 and 99 in P9426). Another limitation was the fact that neither study was designed to distinguish between children and adolescents/young adults, she said.
The investigators plan to collaborate with adult oncology groups to standardize treatment of adolescents and young adults, Dr. Fernandez concluded.
In the question and response session following the presentation, Dr. Jonathan Friedberg, chief of hematology/oncology at the University of Rochester (N.Y.), noted that the toxicities associated with therapy are not all drug related.
"Your pediatric group seems to be very focused on decreasing the doses of chemotherapy in an effort to mediate late toxicity, but I think most people would accept that radiation is probably the big driver of late toxicity, and it appears that in these regimens you’re giving radiation to patients with advanced-stage Hodgkin’s," commented Dr. Friedberg, who moderated the session but was not involved in the study.
Dr. Fernandez acknowledged that all patients in the P9425 and P9426 protocols received radiation, but added that the group is currently conducting trials in which radiation will be given based on patient responses determined by PET scans following the first cycle of chemotherapy.
The study was supported by the Children’s Oncology Group. Dr. Fernandez reported that she had no relevant conflicts of interest. Dr. Friedberg reported being a consultant to or receiving honoraria from Genentech, Astellas, Lilly, Trubion, Seattle Genetics, and Cephalon.
SAN DIEGO – Adolescents and young adults with Hodgkin’s lymphoma can have high response rates and durable remissions under protocols developed for children, with potentially lower long-term toxicities than those commonly seen with adult-oriented regimens, said investigators at the annual meeting of the American Society of Hematology.
The 15- to 20-year-olds with Hodgkin’s lymphoma who were treated under two similar Children’s Oncology Group protocols had a 5-year event-free survival rate of 85.9%, compared with 87.0% for patients younger than 15 years. The 10-year rate was 77.3% in the older patients and 83.8% in the younger group (P = .515), reported Dr. Karen S. Fernandez of the pediatrics department at the University of Illinois, Peoria.
These 5-year event-free survival results are comparable to outcomes of other studies in which adolescents and young adults were treated with adult cooperative-group protocols. Moreover, the cumulative doses of alkylators, anthracyclines, and etoposide used are below thresholds usually associated with significant long-term toxicities, Dr. Fernandez noted.
"Based on this data, we favor the use of pediatric-focused therapy with dose-limited regimens for adolescents and young adults with Hodgkin’s lymphoma in whom decreasing long-term effects is important to improve quality of life, particularly for adolescents with advanced stages," she said.
There is no widely accepted standard of treatment for adolescents and young adults with Hodgkin’s lymphoma, in part because different centers variously treat teens with adult or pediatric protocols, and published data specifically regarding the treatment of adolescents and young adults with Hodgkin’s lymphoma are scarce, Dr. Fernandez said.
She and her colleagues in the Children’s Oncology Group tried to find a balance between maximum possible cure rates and reduced long-term effects by conducting a retrospective analysis comparing children younger than 15 years with adolescents and young adults aged 15-20 years, in the Children’s Oncology Group protocols P9425 and P9426.
The P9425 study looked at the ABVE-PC regimen (doxorubicin [Adriamycin], bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide in dose-dense application) in patients with advanced-stage Hodgkin’s lymphoma. P9426 evaluated the ABVE regimen (the same combination, also dose-dense but without prednisone or cyclophosphamide) in patients with low-stage Hodgkin’s lymphoma.
Patients with an early response in P9425 received 21 Gy of radiation after three cycles of ABVE-PC spaced 21 days apart; patients with a slow response received the same radiation dose after five cycles.
In the P9426 protocol, patients with early responses received 25 Gy after two cycles, while all others received the same radiation dose after four cycles of ABVE. Patients in both protocols received dexrazoxane at the investigators’ discretion.
The cumulative chemotherapy doses delivered in the ABVE and ABVE-PC regimens in these trials were significantly lower than those delivered in other trials of patients with standard or high- to intermediate-risk Hodgkin’s disease, including the BEACOPP regimen (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine [Oncovin], prednisone, and procarbazine), COPP-ABVD (the same drugs as BEACOPP plus vinblastine and dacarbazine), and ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine).
When Dr. Fernandez and her colleagues conducted a Cox regression analysis of patients in the combined studies, they found that neither sex, histologic subtypes, nor tumor staging was predictive of outcomes.
She noted that the study was limited by the retrospective design and the small number of adolescents in each group (104 in P9425 and 99 in P9426). Another limitation was the fact that neither study was designed to distinguish between children and adolescents/young adults, she said.
The investigators plan to collaborate with adult oncology groups to standardize treatment of adolescents and young adults, Dr. Fernandez concluded.
In the question and response session following the presentation, Dr. Jonathan Friedberg, chief of hematology/oncology at the University of Rochester (N.Y.), noted that the toxicities associated with therapy are not all drug related.
"Your pediatric group seems to be very focused on decreasing the doses of chemotherapy in an effort to mediate late toxicity, but I think most people would accept that radiation is probably the big driver of late toxicity, and it appears that in these regimens you’re giving radiation to patients with advanced-stage Hodgkin’s," commented Dr. Friedberg, who moderated the session but was not involved in the study.
Dr. Fernandez acknowledged that all patients in the P9425 and P9426 protocols received radiation, but added that the group is currently conducting trials in which radiation will be given based on patient responses determined by PET scans following the first cycle of chemotherapy.
The study was supported by the Children’s Oncology Group. Dr. Fernandez reported that she had no relevant conflicts of interest. Dr. Friedberg reported being a consultant to or receiving honoraria from Genentech, Astellas, Lilly, Trubion, Seattle Genetics, and Cephalon.
FROM THE ANNUAL MEETING OF THE AMERICAN SOCIETY OF HEMATOLOGY
Major Finding: Adolescents and young adults with Hodgkin’s lymphoma who were treated under two similar Children’s Oncology Group protocols had a 5-year event-free survival (EFS) rate of 85.9%, compared with 87.0% for patients younger than 15 years, and a 10-year EFS rate of 77.3% compared with 83.8% (P = .515).
Data Source: A retrospective analysis of two published trials.
Disclosures: The study was supported by the Children’s Oncology Group. Dr. Fernandez reported that she had no relevant conflicts of interest. Dr. Friedberg reported being a consultant to or receiving honoraria from Genentech, Astellas, Lilly, Trubion, Seattle Genetics, and Cephalon.