An individual patient-data comparison of combined modality therapy and ABVD alone for patients with limited-stage Hodgkin lymphoma

Ann Oncol. 2013 Dec;24(12):3065-9. doi: 10.1093/annonc/mdt389. Epub 2013 Oct 11.

Abstract

Background: Treatment options for patients with nonbulky stage IA-IIA Hodgkin lymphoma include combined modality therapy (CMT) using doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) plus involved-field radiation therapy (IFRT), and chemotherapy with ABVD alone. There are no mature randomized data comparing ABVD with CMT using modern radiation techniques.

Patients and methods: Using German Hodgkin Study Group HD10/HD11 and NCIC Clinical Trials Group HD.6 databases, we identified 588 patients who met mutually inclusive eligibility criteria from the preferred arms of HD10 or 11 (n = 406) and HD.6 (n = 182). We evaluated time to progression (TTP), progression-free (PFS) and overall survival, including in three predefined exploratory subset analyses.

Results: With median follow-up of 91 (HD10/11) and 134 (HD.6) months, respective 8-year outcomes were for TTP, 93% versus 87% [hazard ratio (HR) 0.44, 95% confidence interval (CI) 0.24-0.78]; for PFS, 89% versus 86% (HR 0.71, 95% CI 0.42-1.18) and for overall survival, 95% versus 95% (HR 1.09, 95% CI 0.49-2.40). In the exploratory subset analysis including HD10 eligible patients who achieved complete response (CR) or unconfirmed complete response (CRu) after two cycles of ABVD, 8-year PFS was 87% (HD10) versus 95% (HD.6) (HR 2.8; 95% CI 0.64-12.5) and overall survival 96% versus 100%. In contrast, among those without CR/CRu after two cycles of ABVD, 8-year PFS was 88% versus 74% (HR 0.35; 95% CI 0.16-0.79) and overall survival 95% versus 91%, respectively (HR 0.42; 95% CI 0.12-1.44).

Conclusions: In patients with nonbulky stage IA-IIA Hodgkin lymphoma, CMT provides better disease control than ABVD alone, especially among those not achieving complete response after two cycles of ABVD. Within the follow-up duration evaluated, overall survivals were similar. Longer follow-up is required to understand the implications of radiation and chemotherapy-related late effects.

Clinical trials: The trials included in this analysis were registered at ClinicalTrials.gov: HD10 - NCT00265018, HD11 - NCT00264953, HD.6 - NCT00002561.

Keywords: Hodgkin lymphoma; chemotherapy; clinical trial; combined modality therapy; progression-free survival; radiation therapy.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bleomycin / therapeutic use
  • Chemoradiotherapy
  • Dacarbazine / therapeutic use
  • Disease-Free Survival
  • Doxorubicin / therapeutic use
  • Hodgkin Disease / drug therapy*
  • Hodgkin Disease / mortality
  • Humans
  • Proportional Hazards Models
  • Randomized Controlled Trials as Topic
  • Retrospective Studies
  • Treatment Outcome
  • Vinblastine / therapeutic use

Substances

  • Bleomycin
  • Vinblastine
  • Dacarbazine
  • Doxorubicin

Supplementary concepts

  • ABVD protocol

Associated data

  • ClinicalTrials.gov/NCT00002561
  • ClinicalTrials.gov/NCT00264953
  • ClinicalTrials.gov/NCT00265018