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

J Clin Oncol. 2015 Jun 10;33(17):1936-42. doi: 10.1200/JCO.2014.57.8138. Epub 2015 Apr 20.

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.

Trial registration: ClinicalTrials.gov NCT00003389.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bleomycin / administration & dosage
  • Chemotherapy, Adjuvant
  • Cyclophosphamide / administration & dosage
  • Dacarbazine / administration & dosage
  • Disease-Free Survival
  • Doxorubicin / administration & dosage
  • Etoposide / administration & dosage
  • Female
  • Hodgkin Disease / drug therapy*
  • Hodgkin Disease / pathology
  • Hodgkin Disease / radiotherapy*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Mechlorethamine / administration & dosage
  • Mediastinal Neoplasms / drug therapy*
  • Mediastinal Neoplasms / pathology
  • Mediastinal Neoplasms / radiotherapy*
  • Middle Aged
  • Neoplasm Staging
  • North America
  • Prednisone / administration & dosage
  • Procarbazine / administration & dosage
  • Radiotherapy, Adjuvant
  • Risk Factors
  • Treatment Outcome
  • Vinblastine / administration & dosage
  • Vincristine / administration & dosage

Substances

  • Bleomycin
  • Procarbazine
  • Mechlorethamine
  • Vincristine
  • Vinblastine
  • Etoposide
  • Dacarbazine
  • Doxorubicin
  • Cyclophosphamide
  • Prednisone

Supplementary concepts

  • ABVD protocol
  • BEACOPP protocol
  • Stanford V protocol

Associated data

  • ClinicalTrials.gov/NCT00003389