Chemotherapy dose intensity correlates strongly with response, median survival, and median progression-free survival in metastatic neuroblastoma

Abstract

We examined the efficacy of five commonly used drugs, teniposide (VM26), cisplatin (CDDP), cyclophosphamide (CPM), doxorubicin (DOXO), and vincristine (VCR) in a retrospective analysis of 44 clinical trials of induction chemotherapy for stage IV neuroblastoma patients newly diagnosed at older than 1 year of age. Dose intensity (DI) of each drug was calculated as milligrams per square meter per week. Linear regression analyses showed that the Dls of VM26 and CDDP had the greatest influence on clinical outcomes (ie, proportion of major response, median survival, and median progression-free survival [PFS]), while those of CPM and DOXO were less significant. VCR had no influence on the three clinical end points. Although many protocols extended treatment to more than 1 year, none of these end points correlated positively with the duration of therapy. Twenty-one weeks appeared adequate for achieving superior response, median survival, and median PFS. These results suggest that maximal dose intensification of selective drugs over a short duration may improve the outcome of patients with poor-risk neuroblastoma.