Moderate dose escalation for advanced stage Hodgkin's disease using the bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone scheme and adjuvant radiotherapy: a study of the German Hodgkin's Lymphoma Study Group.
The BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone) regimen, a rearranged and accelerated version of the standard COPP/adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy, has been shown to be effective and safe in a previous pilot study for advanced stage Hodgkin's disease (HD). The present study aimed to determine a maximum practicable dose of three drugs, ie, etoposide, adriamycin, and cyclophosphamide, for which acute toxicities were acceptable and to assess the feasibility of the escalated scheme. Sixty untreated patients with advanced stage HD were enrolled in this study. Radiotherapy was given in 44 patients (73%) after chemotherapy to initial bulk lesions and residual disease. Granulocyte-colony stimulating factor (G-CSF) was given from day 8 to prevent prolonged neutrocytopenia and severe infections. The intended doses of adriamycin, etoposide, and cyclophosphamide in the BEACOPP schedule could be substantially escalated: adriamycin from 25 to 35, cyclophosphamide from 650 to 1,200, and etoposide from 100 to 200 mg/m2. The major toxicities were leukocytopenia and thrombocytopenia with considerable heterogeneity between individual patients. Of 60 patients, 56 (93%) achieved a complete remission (CR). At a median observation of 32 months, the rates of survival and freedom from treatment failure (FFTF) were estimated to be 91% (95% confidence interval 83% to 99%) and 90% (82% to 98%). These results show that a moderate dose escalation of adriamycin, cyclophosphamide, and etoposide of the baseline BEACOPP regimen is feasible. The escalated BEACOPP regimen shows very encouraging results in advanced stage HD and is now being compared in a randomized phase III study with BEACOPP at baseline dose level.
Tesch
H
H
Klinik I für Innere Medizin, Universität Köln, Köln, Germany.
Diehl
V
V
Lathan
B
B
Hasenclever
D
D
Sieber
M
M
Rüffer
U
U
Engert
A
A
Franklin
J
J
Pfreundschuh
M
M
Schalk
K P
KP
Schwieder
G
G
Wulf
G
G
Dölken
G
G
Worst
P
P
Koch
P
P
Schmitz
N
N
Bruntsch
U
U
Tirier
C
C
Müller
U
U
Loeffler
M
M
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D001761:Bleomycin / Q000008:administration & dosage / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000627:therapeutic use; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D006801:Humans; D007938:Leukemia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000139:chemically induced; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D011344:Procarbazine / Q000008:administration & dosage / Q000009:adverse effects; D018714:Radiotherapy, Adjuvant; D011994:Recombinant Proteins; D012074:Remission Induction; D015996:Survival Rate; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
D011994:Recombinant Proteins; D001761:Bleomycin; D016179:Granulocyte Colony-Stimulating Factor; D011344:Procarbazine; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D000069585:Filgrastim; D011241:Prednisone