PREIRRADIATION CHEMOTHERAPY INCLUDING 8-DRUGS-IN-1-DAY REGIMEN AND HIGH-DOSE METHOTREXATE IN CHILDHOOD MEDULLOBLASTOMA - RESULTS OF THE M7 FRENCH COOPERATIVE STUDY

The aim of this study was to evaluate the feasibility and efficacy of a protocol that includes ''sandwich'' chemotherapy, that is, chemother apy alternated with radiotherapy, and reduced doses of supratentorial irradiation in children with medulloblastoma. Between March 1985 and S eptember 1988, 70 successive children with newly diagnosed medulloblas toma from eight centers were treated in this prospective nonrandomized study. Patients were assigned to two risk groups. Group A included pa tients with macroscopically complete or subtotal excision, no brainste m involvement, no atypical cells in the cerebrospinal fluid, normal my elography, and who were more than 2 years of age. Group B patients enc ompassed those who did not fit the criteria for Group A. Two children were excluded from analysis after histological review confirmed ependy moma. Thus, a population of 68 children was selected, with 31 in Group A and 37 in Group B. Treatment consisted of two courses of the ''eigh t drugs in 1 day'' (''8/1'') regimen followed by two courses of high-d ose methotrexate (12 g/m(2)). Radiotherapy was begun during the 7th we ek after surgery in Group A and during the 5th week in Group B. in pat ients older than 2 years, the median radiation dose to the posterior f ossa, the spinal axis, and the brain was 54 Gy, 36 Gy, and 27 Gy, resp ectively. Group B patients received postirradiation chemotherapy with four 8/1 courses monthly. The median time from surgery to radiation th erapy was 50 days (range 21 to 141 days). One fatality due to chicken pox on Day 102 and one World Health Organization Grade IV infection oc curred. The estimated 5- and 7-year disease-free survival (DFS) rates were 62% and 59%, respectively. These were 74% and 62% in Group A and 57% and 57% in Group B. Patient age, extent of resection, and radiatio n dose to the whole brain had no prognostic value. Patients with metas tasis had a nonsignificant trend for a worse prognosis than patients w ith nonmetastatic disease (7-year DFS 45% vs. 68%, p = 0.11). In Group B, the 7-year DFS rates for children who received more or less than 3 0 Gy to the brain were 69% and 52% respectively (p = 0.15). There were recurrences in the posterior fossa (37%), spine (20%), and brain (20% ). After a review of radiotherapeutic treatments, only one supratentor ial failure could be blamed on reduction of the supratentorial radiati on dose. This ''sandwich'' chemotherapy appeared to be feasible and di d not show adverse survival data when compared to other series.