Early versus late intensification for patients with high-risk Hodgkin lymphoma-3 cycles of intensive chemotherapy plus low-dose lymph node radiation therapy versus 4 cycles of combined doxorubicin, bleomycin, vinblastine, and dacarbazine plus myeloablative chemotherapy with autologous stem cell transplantation: five-year results of a randomized trial on behalf of the GOELAMS Group.
BACKGROUND
The 5-year freedom from treatment failure (FFTF) rate, with treatment failure defined as the lack of post-treatment complete remission (CR), recurrence, or death, ranges from 60% to 70% after 6 to 8 cycles of combined doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), which is the reference treatment for patients with advanced Hodgkin lymphoma (HL). In this randomized, phase 2 study, the authors tested 2 intensive chemotherapy regimens in 158 patients with clinical stage (CS) IIB through IV HL accompanied by high-risk factors who were recruited between May 1997 and December 2004.


METHODS
High-risk CS IIB, III, and IV were defined by the presence of > or =5 involved lymphoid areas, and/or a mediastinal mass ratio > or =0.45, and/or > or =2 extra lymph node sites affected by the disease (for CS IV). In Arm V, 82 patients received 3 courses of combined vindesine (5 mg/m(2)), doxorubicin (99 mg/m(2)), carmustine (140 mg/m(2)), etoposide (600 mg/m(2)), and methylprednisolone (600 mg/m(2)) (VABEM) followed by low-dose lymph node irradiation. In Arm A, 76 patients received 4 cycles of ABVD followed by myeloablative combined carmustine (300 mg/m(2)), etoposide (800 mg/m(2)), cytarabine (1600 mg/m(2)), and melphalan (140 mg/m(2)) and underwent autologous stem cell transplantation.


RESULTS
After 3 cycles of VABEM, the CR rate was 89% versus 60% after 4 cycles of ABVD. However, after the completion of treatment, the CR rates for Arms V and A were similar (89% and 88%, respectively). The 5-year FFTF rates for Arms V and A also were similar (79% and 75%, respectively) along with the 5-year overall survival rates (87% and 86%, respectively).


CONCLUSIONS
Early intensification (Arm V) and late intensification (Arm A) were equally effective for treating patients with high-risk/advanced HL.
Arakelyan
Nina
N
University of Paris-Descartes, Paris, France.
Berthou
Christian
C
Desablens
Bernard
B
de Guibert
Sophie
S
Delwail
Vincent
V
Moles
Marie-Pierre
MP
Quittet
Philippe
P
Jais
Jean-Philippe
JP
Colonna
Pierre
P
Andrieu
Jean-Marie
JM
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001761:Bleomycin / Q000627:therapeutic use; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use; D005047:Etoposide / Q000627:therapeutic use; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006689:Hodgkin Disease / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D006801:Humans; D015182:Lymphatic Irradiation; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage; D011241:Prednisone / Q000627:therapeutic use; D016896:Treatment Outcome; D014747:Vinblastine / Q000627:therapeutic use; D014750:Vincristine / Q000627:therapeutic use
D001761:Bleomycin; D014750:Vincristine; D014747:Vinblastine; D005047:Etoposide; D003606:Dacarbazine; D004317:Doxorubicin; D011241:Prednisone; D008775:Methylprednisolone