Originally published as JCO Early Release 10.1200/JCO.2005.03.2151 on November 28 2005

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Comparison of ABVD and Alternating or Hybrid Multidrug Regimens for the Treatment of Advanced Hodgkin's Lymphoma: Results of the United Kingdom Lymphoma Group LY09 Trial (ISRCTN97144519)

From the Cancer Research UK Clinical Centre, Southampton General Hospital, Southampton; Cancer Research UK Department of Medical Oncology, Christie Hospital, Manchester; Department of Medical Oncology, Queen Elizabeth Hospital, Birmingham; Medical Research Council Clinical Trials Unit; Lymphoma Trials Office, Cancer Research UK/University College London Trials Unit, London; Hematologic Malignancy Diagnosis Service, The General Infirmary, Leeds; Yorkshire Cancer Research Academic Unit of Clinical Oncology, Weston Park Hospital, Sheffield, United Kingdom; and Maria Sklodowska-Curie Memorial Cancer Centre, Warsaw, Poland; on behalf of the UKLG LY09 Collaborators

Address reprint requests to Peter W.M. Johnson, MD, FRCP, Cancer Research UK Clinical Centre, Somers Cancer Research Building, MP824, Southampton General Hospital, Southampton SO16 6YD, United Kingdom; e-mail: johnsonp{at}soton.ac.uk

PURPOSE: To perform an open-label, randomized, controlled trial comparing treatment with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) with two multidrug regimens (MDRs) for advanced Hodgkin's lymphoma (HL).

PATIENTS AND METHODS: Eight hundred seven patients with advanced HL (stage III to IV, or earlier stage with systemic symptoms or bulky disease) were randomly assigned between ABVD and MDR specified before randomization as alternating chlorambucil, vinblastine, procarbazine, and prednisolone (ChlVPP) with prednisolone, doxorubicin, bleomycin, vincristine, and etoposide (PABIOE), or hybrid ChlVPP/etoposide, vincristine, and doxorubicin (EVA). Radiotherapy was planned for incomplete response or initial bulk disease.

RESULTS: At 52 months median follow-up, 212 event-free survival (EFS) events (disease progression or any death) were reported. In the primary comparison, at 3 years EFS was 75% (95% CI, 71% to 79%) for ABVD and 75% (95% CI, 70% to 79%) for MDRs (hazard ratio [HR] = 1.05; 95% CI, 0.8 to 1.37; HR more than 1.0 favors ABVD). The 3-year overall survival (OS) rates were 90% (95% CI, 87% to 93%) in patients allocated ABVD and 88% (95% CI, 84% to 91%) in patients allocated MDRs (HR = 1.22; 95% CI, 0.84 to 1.77). Patients receiving MDRs experienced more grade 3/4 infection, mucositis, and neuropathy. One occurrence of myelodysplastic syndrome was reported, but no acute leukemia was reported. When the two MDRs are compared separately with ABVD, neither the alternating nor the hybrid regimen showed a statistically significant difference from ABVD for EFS or OS. Subgroup analysis suggested that MDRs may be associated with poorer outcomes in older patients (heterogeneity test of OS older or younger than 45 years, P = .020).

CONCLUSION: There was no evidence of significant difference in EFS or OS between ABVD and MDRs in the trial overall or if the two MDR versus ABVD comparisons are considered separately. ABVD remains the standard for treatment of advanced HL.

Supported by a research grant from the UK Cancer Research Campaign (now Cancer Research UK).

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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