High cure rates and reduced long-term toxicity in pediatric Hodgkin's disease: The German-Austrian multicenter trial DAL-HD-90

Purpose: To further reduce therapy-related late effects in patients with pe diatric Hodgkin's disease (HD) while maintaining the high cure rates achiev ed with vincristine, prednisone, procarbazine, and doxorubicin (OPPA) or OP PA/cyclophosphamide, vincristine, prednisone, and procarbazine (COPP) chemo therapy and involved-field radiotherapy. The risk of testicular dysfunction was addressed by substituting etoposide for procarbazine (OEPA) in the ind uction therapy for boys. Radiation doses and fields were further reduced. Patients and Methods: Three hundred nineteen boys and 259 girls younger tha n 18 years with previously untreated HD, enrolled onto the study between 19 90 and 1995, were allocated to treatment group (TG)1 (early stages), TG2 (i ntermediate stages), or TG3 (advanced stages), All groups underwent two cyc les of OEPA (boys) or OPPA (girls) For induction chemotherapy, TG2 and TG3 continued on additional two or four cycles, respectively, of COPP. Low-dose radiotherapy was given to the initially involved sites, ie, reduced involv ed fields. Results: initial response to OPPA or OEPA induction was virtually identical , Eight of 578 patients experienced early progression of HD. Thirty-seven r elapses, three secondary tumors, and no secondary leukemias have been recor ded, with a median follow-up duration of 5.1 years (maximum, 8.1 years), Th irteen of 578 patients died, The probability of S-year event-free survival/ overall survival is 91%/98% in the total group, 94%/97% with OPPA, and 89%/ 98% with OEPA induction therapy, Risk factor analysis showed two significan t prognostic factors: histologic subtype NS2 and "B" symptoms, OEPA inducti on therapy large mediastinal tumor, and age were not significant, prelimina ry studies of testicular function indicate a lower risk of germ cell damage than previously documented with OPPA, Conclusion: OEPA is a satisfactory alternative to OPPA, Radiotherapy can be confined to involved sires when combined with appropriate chemotherapy, Th e DAL-HD-90 regimen represents a comprehensive treatment program for all st ages of pediatric HD and offers a favorable benefit/risk ratio, combining e xcellent disease control, moderate acute toxicity, and reduced longterm tox icity, J Clin Oncol 17:3736-3744. (C) 1999 by American Society of Clinical Oncology.