Rapidly alternating COPP/ABV/IMEP is not superior to conventional alternating COPP/ABVD in combination with extended-field radiotherapy in intermediate-stage Hodgkin's lymphoma: final results of the German Hodgkin's Lymphoma Study Group Trial HD5.
OBJECTIVE
To investigate whether treatment results in intermediate-stage Hodgkin's lymphoma can be improved by rapid application of non-cross-resistant drugs, the 10-drug regimen cyclophosphamide, vincristine, procarbazine, and prednisone (COPP), doxorubicin, bleomycin, and vinblastine (ABV), and ifosfamide, methotrexate, etoposide, and prednisone (IMEP), repeated every 6 weeks, was compared with conventional alternating COPP/doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) administered every 8 weeks.


METHODS
From January 1988 to January 1993, 996 patients in stage I or II Hodgkin's lymphoma with at least one risk factor (massive mediastinal tumor, massive spleen involvement, extranodal disease, elevated ESR, or more than two lymph node areas involved) and all patients in stage IIIA Hodgkin's lymphoma were randomized to receive two cycles of COPP/ABVD or COPP/ABV/IMEP followed by extended-field radiotherapy.


RESULTS
Both regimens produced similar rates for treatment responses (complete remission, 93% v 94%), freedom from treatment failure (80% v 79%), and overall survival (88% for both regimens) at a median follow-up time of 7 years. Most serious toxicities during chemotherapy were similar in both regimens. However, World Health Organization grade 3 and 4 leukocytopenia occurred significantly more frequently in the COPP/ABV/IMEP arm (53% v 44% of patients; P =.010). There were no differences in the number of serious infections and toxic deaths during therapy. The number of second malignancies was also the same in both arms (22 each).


CONCLUSIONS
Alternating COPP/ABVD and rapid alternating COPP/ABV/IMEP in combination with extended-field radiotherapy are equally effective in intermediate-stage Hodgkin's lymphoma and produce excellent long-term treatment results.
Sieber
Markus
M
German Hodgkin's Lymphoma Study Group, Cologne, Germany. markus.sieber@medizin.uni-koeln.de
Tesch
Hans
H
Pfistner
Beate
B
Rueffer
Ulrich
U
Lathan
Bernd
B
Brosteanu
Oana
O
Paulus
Ursula
U
Koch
Tina
T
Pfreundschuh
Michael
M
Loeffler
Markus
M
Engert
Andreas
A
Josting
Andreas
A
Wolf
Jürgen
J
Hasenclever
Dirk
D
Franklin
Jeremy
J
Duehmke
Eckhart
E
Georgii
Axel
A
Schalk
Klaus-Peter
KP
Kirchner
Hartmut
H
Doelken
Gottfried
G
Munker
Reinhold
R
Koch
Peter
P
Herrmann
Richard
R
Greil
Richard
R
Anselmo
Anna Paola
AP
Diehl
Volker
V
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; D003520:Cyclophosphamide / Q000008:administration & dosage; D003606:Dacarbazine / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage; D011344:Procarbazine / Q000008:administration & dosage; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage; D014750:Vincristine / Q000008:administration & dosage
D001761:Bleomycin; D011344:Procarbazine; D014750:Vincristine; D014747:Vinblastine; D005047:Etoposide; D003606:Dacarbazine; D004317:Doxorubicin; D003520:Cyclophosphamide; D007069:Ifosfamide; D011241:Prednisone; D008727:Methotrexate