Randomized phase III trial comparing ABVD plus radiotherapy with the Stanford V regimen in patients with stages I or II locally extensive, bulky mediastinal Hodgkin lymphoma: A subset analysis of the North American Intergroup E2496 trial

Ranjana H. Advani, Fangxin Hong, Richard I. Fisher, Nancy L. Bartlett, K. Sue Robinson, Randy D. Gascoyne, Henry Wagner, Patrick J. Stiff, Bruce D. Cheson, Douglas A. Stewart, Leo I. Gordon, Brad S. Kahl, Jonathan W. Friedberg, Kristie A. Blum, Thomas M. Habermann, Joseph M. Tuscano, Richard T. Hoppe, Sandra J. Horning

Research output: Contribution to journalArticle

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Abstract

Purpose: The phase III North American Intergroup E2496 Trial (Combination Chemotherapy With or Without Radiation Therapy in Treating Patients With Hodgkin's Lymphoma) compared doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) with mechlorethamine, doxorubicin, vincristine, bleomycin, vinblastine, etoposide, and prednisone (Stanford V). We report results of a planned subgroup analysis in patients with stage I or II bulky mediastinal Hodgkin lymphoma (HL). Patients and Methods: Patients were randomly assigned to six to eight cycles of ABVD every 28 days or Stanford V once per week for 12 weeks. Two to 3 weeks after completion of chemotherapy, all patients received 36 Gy of modified involved field radiotherapy (IFRT) to the mediastinum, hila, and supraclavicular regions. Patients on the Stanford V arm received IFRT to additional sites ≥ 5 cm at diagnosis. Primary end points were failure-free survival (FFS) and overall survival (OS). Results: Of 794 eligible patients, 264 had stage I or II bulky disease, 135 received ABVD, and 129 received Stanford V. Patient characteristics were matched. The overall response rate was 83% with ABVD and 88% with Stanford V. At a median follow-up of 6.5 years, the study excluded a difference of more than 21% in 5-year FFS and more than 16% in 5-year OS between ABVD and Stanford V (5-year FFS: 85% v 79%; HR, 0.68; 95% CI, 0.37 to 1.25; P = .22; 5-year OS: 96% v 92%; HR, 0.49; 95% CI, 0.16 to 1.47; P = .19). In-field relapses occurred in < 10% of the patients in each arm. Conclusion: For patients with stage I or II bulky mediastinal HL, no substantial statistically significant differences were detected between the two regimens, although power was limited. To the best of our knowledge, this is the first prospective trial reporting outcomes specific to this subgroup, and it sets a benchmark for comparison of ongoing and future studies.

Original languageEnglish (US)
Pages (from-to)1936-1942
Number of pages7
JournalJournal of Clinical Oncology
Volume33
Issue number17
DOIs
StatePublished - Jun 10 2015

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Hodgkin Disease
Radiotherapy
Survival
Vinblastine
Bleomycin
Doxorubicin
Arm
Benchmarking
Mechlorethamine
Dacarbazine
Mediastinum
Vincristine
Etoposide
Prednisone
Combination Drug Therapy
Recurrence
Drug Therapy

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Advani, Ranjana H. ; Hong, Fangxin ; Fisher, Richard I. ; Bartlett, Nancy L. ; Robinson, K. Sue ; Gascoyne, Randy D. ; Wagner, Henry ; Stiff, Patrick J. ; Cheson, Bruce D. ; Stewart, Douglas A. ; Gordon, Leo I. ; Kahl, Brad S. ; Friedberg, Jonathan W. ; Blum, Kristie A. ; Habermann, Thomas M. ; Tuscano, Joseph M. ; Hoppe, Richard T. ; Horning, Sandra J. / Randomized phase III trial comparing ABVD plus radiotherapy with the Stanford V regimen in patients with stages I or II locally extensive, bulky mediastinal Hodgkin lymphoma : A subset analysis of the North American Intergroup E2496 trial. In: Journal of Clinical Oncology. 2015 ; Vol. 33, No. 17. pp. 1936-1942.
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title = "Randomized phase III trial comparing ABVD plus radiotherapy with the Stanford V regimen in patients with stages I or II locally extensive, bulky mediastinal Hodgkin lymphoma: A subset analysis of the North American Intergroup E2496 trial",
abstract = "Purpose: The phase III North American Intergroup E2496 Trial (Combination Chemotherapy With or Without Radiation Therapy in Treating Patients With Hodgkin's Lymphoma) compared doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) with mechlorethamine, doxorubicin, vincristine, bleomycin, vinblastine, etoposide, and prednisone (Stanford V). We report results of a planned subgroup analysis in patients with stage I or II bulky mediastinal Hodgkin lymphoma (HL). Patients and Methods: Patients were randomly assigned to six to eight cycles of ABVD every 28 days or Stanford V once per week for 12 weeks. Two to 3 weeks after completion of chemotherapy, all patients received 36 Gy of modified involved field radiotherapy (IFRT) to the mediastinum, hila, and supraclavicular regions. Patients on the Stanford V arm received IFRT to additional sites ≥ 5 cm at diagnosis. Primary end points were failure-free survival (FFS) and overall survival (OS). Results: Of 794 eligible patients, 264 had stage I or II bulky disease, 135 received ABVD, and 129 received Stanford V. Patient characteristics were matched. The overall response rate was 83{\%} with ABVD and 88{\%} with Stanford V. At a median follow-up of 6.5 years, the study excluded a difference of more than 21{\%} in 5-year FFS and more than 16{\%} in 5-year OS between ABVD and Stanford V (5-year FFS: 85{\%} v 79{\%}; HR, 0.68; 95{\%} CI, 0.37 to 1.25; P = .22; 5-year OS: 96{\%} v 92{\%}; HR, 0.49; 95{\%} CI, 0.16 to 1.47; P = .19). In-field relapses occurred in < 10{\%} of the patients in each arm. Conclusion: For patients with stage I or II bulky mediastinal HL, no substantial statistically significant differences were detected between the two regimens, although power was limited. To the best of our knowledge, this is the first prospective trial reporting outcomes specific to this subgroup, and it sets a benchmark for comparison of ongoing and future studies.",
author = "Advani, {Ranjana H.} and Fangxin Hong and Fisher, {Richard I.} and Bartlett, {Nancy L.} and Robinson, {K. Sue} and Gascoyne, {Randy D.} and Henry Wagner and Stiff, {Patrick J.} and Cheson, {Bruce D.} and Stewart, {Douglas A.} and Gordon, {Leo I.} and Kahl, {Brad S.} and Friedberg, {Jonathan W.} and Blum, {Kristie A.} and Habermann, {Thomas M.} and Tuscano, {Joseph M.} and Hoppe, {Richard T.} and Horning, {Sandra J.}",
year = "2015",
month = "6",
day = "10",
doi = "10.1200/JCO.2014.57.8138",
language = "English (US)",
volume = "33",
pages = "1936--1942",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
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Advani, RH, Hong, F, Fisher, RI, Bartlett, NL, Robinson, KS, Gascoyne, RD, Wagner, H, Stiff, PJ, Cheson, BD, Stewart, DA, Gordon, LI, Kahl, BS, Friedberg, JW, Blum, KA, Habermann, TM, Tuscano, JM, Hoppe, RT & Horning, SJ 2015, 'Randomized phase III trial comparing ABVD plus radiotherapy with the Stanford V regimen in patients with stages I or II locally extensive, bulky mediastinal Hodgkin lymphoma: A subset analysis of the North American Intergroup E2496 trial', Journal of Clinical Oncology, vol. 33, no. 17, pp. 1936-1942. https://doi.org/10.1200/JCO.2014.57.8138

Randomized phase III trial comparing ABVD plus radiotherapy with the Stanford V regimen in patients with stages I or II locally extensive, bulky mediastinal Hodgkin lymphoma : A subset analysis of the North American Intergroup E2496 trial. / Advani, Ranjana H.; Hong, Fangxin; Fisher, Richard I.; Bartlett, Nancy L.; Robinson, K. Sue; Gascoyne, Randy D.; Wagner, Henry; Stiff, Patrick J.; Cheson, Bruce D.; Stewart, Douglas A.; Gordon, Leo I.; Kahl, Brad S.; Friedberg, Jonathan W.; Blum, Kristie A.; Habermann, Thomas M.; Tuscano, Joseph M.; Hoppe, Richard T.; Horning, Sandra J.

In: Journal of Clinical Oncology, Vol. 33, No. 17, 10.06.2015, p. 1936-1942.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Randomized phase III trial comparing ABVD plus radiotherapy with the Stanford V regimen in patients with stages I or II locally extensive, bulky mediastinal Hodgkin lymphoma

T2 - A subset analysis of the North American Intergroup E2496 trial

AU - Advani, Ranjana H.

AU - Hong, Fangxin

AU - Fisher, Richard I.

AU - Bartlett, Nancy L.

AU - Robinson, K. Sue

AU - Gascoyne, Randy D.

AU - Wagner, Henry

AU - Stiff, Patrick J.

AU - Cheson, Bruce D.

AU - Stewart, Douglas A.

AU - Gordon, Leo I.

AU - Kahl, Brad S.

AU - Friedberg, Jonathan W.

AU - Blum, Kristie A.

AU - Habermann, Thomas M.

AU - Tuscano, Joseph M.

AU - Hoppe, Richard T.

AU - Horning, Sandra J.

PY - 2015/6/10

Y1 - 2015/6/10

N2 - Purpose: The phase III North American Intergroup E2496 Trial (Combination Chemotherapy With or Without Radiation Therapy in Treating Patients With Hodgkin's Lymphoma) compared doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) with mechlorethamine, doxorubicin, vincristine, bleomycin, vinblastine, etoposide, and prednisone (Stanford V). We report results of a planned subgroup analysis in patients with stage I or II bulky mediastinal Hodgkin lymphoma (HL). Patients and Methods: Patients were randomly assigned to six to eight cycles of ABVD every 28 days or Stanford V once per week for 12 weeks. Two to 3 weeks after completion of chemotherapy, all patients received 36 Gy of modified involved field radiotherapy (IFRT) to the mediastinum, hila, and supraclavicular regions. Patients on the Stanford V arm received IFRT to additional sites ≥ 5 cm at diagnosis. Primary end points were failure-free survival (FFS) and overall survival (OS). Results: Of 794 eligible patients, 264 had stage I or II bulky disease, 135 received ABVD, and 129 received Stanford V. Patient characteristics were matched. The overall response rate was 83% with ABVD and 88% with Stanford V. At a median follow-up of 6.5 years, the study excluded a difference of more than 21% in 5-year FFS and more than 16% in 5-year OS between ABVD and Stanford V (5-year FFS: 85% v 79%; HR, 0.68; 95% CI, 0.37 to 1.25; P = .22; 5-year OS: 96% v 92%; HR, 0.49; 95% CI, 0.16 to 1.47; P = .19). In-field relapses occurred in < 10% of the patients in each arm. Conclusion: For patients with stage I or II bulky mediastinal HL, no substantial statistically significant differences were detected between the two regimens, although power was limited. To the best of our knowledge, this is the first prospective trial reporting outcomes specific to this subgroup, and it sets a benchmark for comparison of ongoing and future studies.

AB - Purpose: The phase III North American Intergroup E2496 Trial (Combination Chemotherapy With or Without Radiation Therapy in Treating Patients With Hodgkin's Lymphoma) compared doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) with mechlorethamine, doxorubicin, vincristine, bleomycin, vinblastine, etoposide, and prednisone (Stanford V). We report results of a planned subgroup analysis in patients with stage I or II bulky mediastinal Hodgkin lymphoma (HL). Patients and Methods: Patients were randomly assigned to six to eight cycles of ABVD every 28 days or Stanford V once per week for 12 weeks. Two to 3 weeks after completion of chemotherapy, all patients received 36 Gy of modified involved field radiotherapy (IFRT) to the mediastinum, hila, and supraclavicular regions. Patients on the Stanford V arm received IFRT to additional sites ≥ 5 cm at diagnosis. Primary end points were failure-free survival (FFS) and overall survival (OS). Results: Of 794 eligible patients, 264 had stage I or II bulky disease, 135 received ABVD, and 129 received Stanford V. Patient characteristics were matched. The overall response rate was 83% with ABVD and 88% with Stanford V. At a median follow-up of 6.5 years, the study excluded a difference of more than 21% in 5-year FFS and more than 16% in 5-year OS between ABVD and Stanford V (5-year FFS: 85% v 79%; HR, 0.68; 95% CI, 0.37 to 1.25; P = .22; 5-year OS: 96% v 92%; HR, 0.49; 95% CI, 0.16 to 1.47; P = .19). In-field relapses occurred in < 10% of the patients in each arm. Conclusion: For patients with stage I or II bulky mediastinal HL, no substantial statistically significant differences were detected between the two regimens, although power was limited. To the best of our knowledge, this is the first prospective trial reporting outcomes specific to this subgroup, and it sets a benchmark for comparison of ongoing and future studies.

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