Risk-adapted, combined-modality therapy with VAMP/COP and response-based, involved-field radiation for unfavorable pediatric Hodgkin's disease.
OBJECTIVE
To evaluate the efficacy of vinblastine, doxorubicin, methotrexate, and prednisone (VAMP) and cyclophosphamide, vincristine, and procarbazine (COP) chemotherapy and response-based, involved-field radiation, a combined-modality regimen that limits doses of alkylating agents, anthracyclines, and radiation, in children with advanced and unfavorable Hodgkin's disease.


METHODS
From 1993 to 2000, 159 children and adolescents with unfavorable Hodgkin's disease received three alternating cycles (total of six cycles) of VAMP/COP chemotherapy followed by response-based, involved-field radiation therapy: 15 Gy was administered to patients achieving a complete response, and 25.5 Gy was administered to those achieving a partial response after the first two cycles of chemotherapy and to all sites of bulky lymphadenopathy. Unfavorable disease was defined as clinical stage I and II with bulky peripheral nodal disease greater than 6 cm, initial bulky mediastinal mass 33% or more of the intrathoracic diameter, and/or "B" symptoms and all stage III and IV.


RESULTS
Study enrollment was closed after an interim analysis estimated a 5-year event-free survival (EFS) rate below a predefined level. Disease presentation was localized (stage I/II) in 77 patients (48.4%) and advanced (stage III/IV) in 82 patients (51.6%). At a median follow-up of 5.8 years (range, 1.3 to 10.0 years), 38 patients had events, including relapse/progression (n = 35), second malignancy (n = 2), and accidental death (n = 1); nine relapses (25.7%) occurred greater than 4 years from diagnosis. Five-year survival and EFS estimates are 92.7% +/- 2.5% and 75.6% +/- 4.1%, respectively.


CONCLUSIONS
Risk-adapted combined-modality therapy with VAMP/COP and response-based, involved-field radiation therapy results in an unsatisfactory outcome for pediatric patients with unfavorable presentations of Hodgkin's disease.
Hudson
Melissa M
MM
Department of Hematology-Oncology, Radiological Sciences and Biostatistics, St Jude Children's Research Hospital and the University of Tennessee College of Medicine, Memphis, TN 38105, USA. melissa.hudson@stjude.org
Krasin
Matthew
M
Link
Michael P
MP
Donaldson
Sarah S
SS
Billups
Catherine
C
Merchant
Thomas E
TE
Kun
Larry
L
Billet
Amy L
AL
Kaste
Sue
S
Tarbell
Nancy J
NJ
Howard
Scott
S
Friedmann
Alison M
AM
Hurwitz
Craig A
CA
Young
Jeffrey A
JA
Marcus
Karen C
KC
Rai
Shesh
S
Cowan
Traci
T
Weinstein
Howard J
HJ
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D018450:Disease Progression; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000473:pathology* / Q000532:radiotherapy; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D011241:Prednisone / Q000008:administration & dosage; D011344:Procarbazine / Q000008:administration & dosage; D011379:Prognosis; D018570:Risk Assessment; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage
D011344:Procarbazine; D014747:Vinblastine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone; D008727:Methotrexate