Epipodophyllotoxins in the treatment of childhood cancer.
We reported marked biologic activity with the epipodophyllotoxins in phase I/II studies of childhood cancer conducted in the 1970s. We have since extensively used the combination of teniposide and ara-C in the treatment of acute lymphoblastic leukemia (ALL). Initially we treated patients with refractory disease and found that the combination lacked clinical cross-resistance with standard antileukemic drugs. This formed a rationale to move teniposide and/or etoposide to front-line therapy of childhood ALL. The superior results projected for our last trial, an overall cure rate of about 75%, are attributable in part to early use of epipodophyllotoxins. This class of agents is also used extensively in the treatment of newly diagnosed childhood solid tumors, including neuroblastoma, medulloblastoma, rhabdomyosarcoma, and germ-cell tumors. Secondary leukemias following treatment with epipodophyllotoxins have been reported in a small subset of patients. Current data show that the most important risk factor is the schedule of drug delivery, which has led to appropriate protocol modifications.
Rivera
G K
GK
Department of Hematology-Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38101.
Pui
C H
CH
Santana
V M
VM
Pratt
C B
CB
Crist
W M
WM
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002648:Child; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D003561:Cytarabine / Q000627:therapeutic use; D005047:Etoposide / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy; D009369:Neoplasms / Q000188:drug therapy*; D016609:Neoplasms, Second Primary / Q000139:chemically induced; D009447:Neuroblastoma / Q000188:drug therapy; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D013713:Teniposide / Q000627:therapeutic use* / Q000633:toxicity
D003561:Cytarabine; D005047:Etoposide; D013713:Teniposide