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Risk-Adapted, Combined-Modality Therapy With VAMP/COP and Response-Based, Involved-Field Radiation for Unfavorable Pediatric Hodgkin's Disease

From the Department of Hematology Oncology, Radiological Sciences, and Biostatistics, St Jude Children's Research Hospital and the University of Tennessee College of Medicine, Memphis, TN; Stanford University Medical Center, Stanford, CA; Massachusetts General Hospital and Dana-Farber Cancer Institute, Boston, MA; and Barbara Bush Children's Hospital at Maine Medical Center, Portland, ME

Address reprint requests to Melissa M. Hudson, MD, St Jude Children's Research Hospital, 332 N Lauderdale, Memphis, TN 38105; e-mail: melissa.hudson{at}stjude.org

PURPOSE: 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.

PATIENTS AND 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.

CONCLUSION: 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.

Supported by Cancer Center Support (CORE) grant No. CA 21765 from the National Cancer Institute and by the American Lebanese Syrian Associated Charities.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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