RANDOMIZED PHASE-III TRIAL IN CHILDHOOD HIGH-GRADE ASTROCYTOMA COMPARING VINCRISTINE, LOMUSTINE, AND PREDNISONE WITH THE 8-DRUGS-IN-1-DAY REGIMEN

Purpose: In a previous randomized trial, the addition of adjuvant chem otherapy to postoperative radiotherapy proved beneficial in the treatm ent of childhood high-grade astrocytomas. The present study tests the hypothesis sis that an eight-drug adjuvant chemotherapy regimen would improve survival in such children compared with the three-drug regimen of the prior study. Patients and Methods: Between April 1985 and May 1990, patients between the ages of 18 months and 21 years with newly d iagnosed high-grade astrocytomas were eligible for this study, as dete rmined by the treating institution's histopathologic diagnosis. Treatm ent consisted of postoperative local-field radiotherapy and adjuvant c hemotherapy, either lomustine (CCNU), vincristine, and prednisone (con trol regimen) or eight-drugs-in-1-day chemotherapy (experimental regim en). Two cycles of postoperative preirradiation chemotherapy were admi nistered in the experimental regimen. Patients were evaluated radiogra phically every 3 months after irradiation. Results: Eighty-five eligib le patients were randomized to the control regimen and 87 to the exper imental regimen. The progression-free survival (PFS) and overall survi val (OS) at 5 years were 33% (SE = 5%) and 36% (SE = 6%), respectively . There was no statistical difference in outcome between the two chemo therapy regimens. In patients with confirmed diagnoses of anaplastic a strocytoma (AA) or glioblastoma multiforme (GEM), anaplastic astrocyto ma, greeter than 90% resection, and nonmidline tumor location were cha racteristics predictive of an improved PFS. There was a difference in toxicity between the two chemotherapeutic regimens, with greeter myelo suppression and hearing loss in the experimental regimen. Tumor recurr ence occurred primarily within the primary tumor site. Conclusions: Th ere is no benefit to the treatment of high rode astrocytomas in childr en with eight-drugs-in-1-day chemotherapy compared with CCNU, vincrist ine, and prednisone. Extent of tumor resection and histopathologic dia gnosis are significant prognostic variables. The overall outcome for c hildren with high-grade astrocytomas remains poor.