Combined-modality therapy for clinical stage I or II Hodgkin's lymphoma: long-term results of the European Organisation for Research and Treatment of Cancer H7 randomized controlled trials.
OBJECTIVE
In early-stage Hodgkin's lymphoma (HL), subtotal nodal irradiation (STNI) and combined chemotherapy/radiotherapy produce high disease control rates but also considerable late toxicity. The aim of this study was to reduce this toxicity using a combination of low-intensity chemotherapy and involved-field radiotherapy (IF-RT) without jeopardizing disease control.


METHODS
Patients with stage I or II HL were stratified into two groups, favorable and unfavorable, based on the following four prognostic factors: age, symptoms, number of involved areas, and mediastinal-thoracic ratio. The experimental therapy consisted of six cycles of epirubicin, bleomycin, vinblastine, and prednisone (EBVP) followed by IF-RT. It was randomly compared, in favorable patients, to STNI and, in unfavorable patients, to six cycles of mechlorethamine, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, and vinblastine (MOPP/ABV hybrid) and IF-RT.


RESULTS
Median follow-up time of the 722 patients included was 9 years. In 333 favorable patients, the 10-year event-free survival rates (EFS) were 88% in the EBVP arm and 78% in the STNI arm (P = .0113), with similar 10-year overall survival (OS) rates (92% v 92%, respectively; P = .79). In 389 unfavorable patients, the 10-year EFS rate was 88% in the MOPP/ABV arm compared with 68% in the EBVP arm (P < .001), leading to 10-year OS rates of 87% and 79%, respectively (P = .0175).


CONCLUSIONS
A treatment strategy for early-stage HL based on prognostic factors leads to high OS rates in both favorable and unfavorable patients. In favorable patients, the combination of EBVP and IF-RT can replace STNI as standard treatment. In unfavorable patients, EBVP is significantly less efficient than MOPP/ABV.
Noordijk
Evert M
EM
Department of Radiotherapy, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands. e.m.noordijk@lumc.nl
Carde
Patrice
P
Dupouy
Noëlle
N
Hagenbeek
Anton
A
Krol
Augustinus D G
AD
Kluin-Nelemans
Johanna C
JC
Tirelli
Umberto
U
Monconduit
Mathieu
M
Thomas
José
J
Eghbali
Houchingue
H
Aleman
Berthe M P
BM
Bosq
Jacques
J
Vovk
Marjeta
M
Verschueren
Tom A M
TA
Pény
Anne-Marie
AM
Girinsky
Théodore
T
Raemaekers
John M M
JM
Henry-Amar
Michel
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001761:Bleomycin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000008:administration & dosage; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008466:Mechlorethamine / Q000008:administration & dosage; D008875:Middle Aged; D009367:Neoplasm Staging; D016609:Neoplasms, Second Primary / Q000139:chemically induced; D011241:Prednisone / Q000008:administration & dosage; D011344:Procarbazine / Q000008:administration & dosage; D016019:Survival Analysis; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage; D014750:Vincristine / Q000008:administration & dosage
D001761:Bleomycin; D011344:Procarbazine; D015251:Epirubicin; D008466:Mechlorethamine; D014750:Vincristine; D014747:Vinblastine; D004317:Doxorubicin; D011241:Prednisone