FRACTIONATED CYCLOPHOSPHAMIDE AND BACK-TO-BACK HIGH-DOSE METHOTREXATEAND CYTOSINE-ARABINOSIDE IMPROVES OUTCOME IN PATIENTS WITH STAGE-III HIGH-GRADE SMALL NON-CLEAVED CELL LYMPHOMAS (SNCCL) - A RANDOMIZED TRIAL OF THE PEDIATRIC-ONCOLOGY-GROUP

Background. The Pediatric Oncology Group (FOG) conducted a two-arm, ra ndomized study for the treatment of children and adolescents with stag e III small, non-cleaved cell lymphoma (SNCCL). Regimen A, based on th e group's previous best treatment for this group of patients, included cyclophosphamide (CTX) and high-dose methotrexate (MTX), as well as v incristine (VCR), prednisone (PRED), and intrathecal (IT) chemoprophyl axis. Regimen B, based on a single institution pilot study (Total B th erapy), consisted of two rapidly alternating chemotherapy combinations (CTX, VCR, doxorubicin; MTX, and cytarabine (Ara-C) plus coordinated IT chemotherapy. Procedure. One hundred thirty-four consecutive patien ts were entered on this study. Seventy patients were randomized to Reg imen A, and 64 patients to Regimen B. One hundred and twenty-two patie nts are eligible for response. Results. Complete remission ICR) was ac hieved by 81% (52/64) of patients on Regimen A, and 95% (55/58) of pat ients on Regimen B (p = 0.014 one-sided). The two-year event-free surv ival (EFS) is 64% (SE = 6%) on Regimen A, and 79% (SE = 6%) on Regimen B (p = 0.027 by one-sided logrank test). No patient has relapsed on e ither regimen after a year from diagnosis, although one patient had a second malignancy at day 371. Severe, but manageable, hematologic toxi city was seen in the majority of patients on both regimens, but was mo re frequent on Regimen B. Conclusions. We conclude that the cure rate in stage III SNCCL is significantly improved with the use of a short, six-month chemotherapy regimen of fractionated CTX alternated with coo rdinated MTX and Ara-C. Results suggest that drug schedule, not simple drug selection, influences outcome. (C) 1997 Wiley-Liss, Inc.