Irinotecan for pediatric solid tumors: the Memorial Sloan-Kettering experience.
OBJECTIVE
Irinotecan is a novel antineoplastic agent that works by inhibiting the enzyme, topoisomerase 1. Although not extensively studied in children, preclinical studies and several phase I trials indicate activity against a variety of relapsed solid tumors when administered on a protracted schedule. This report describes an institutional experience with irinotecan for the treatment of pediatric solid tumors.


METHODS
Twenty-two heavily pretreated children with multiply relapsed tumors were treated with courses of irinotecan at 20 mg/m2 per day for 10 days [(every day x 5) x 2].


RESULTS
Of the 19 patients evaluable for response, four achieved an objective response, including two complete responses and one partial response among four patients with rhabdomyosarcoma and one additional patient with an undifferentiated sarcoma with rhabdomyoblastic features, and one patient with a fibrosarcoma had stable disease. Among three patients with non-Hodgkin lymphoma, one achieved a partial response and one had stable disease. Diarrhea was the most commonly observed toxicity.


CONCLUSIONS
Irinotecan appears to have promising single-agent activity, particularly against rhabdomyosarcoma. with minimal hematopoietic toxicity, making it ideal for further evaluation in patients at high risk with newly diagnosed disease, particularly in combination with other active agents with nonoverlapping toxicities.
Cosetti
Maura
M
Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
Wexler
Leonard H
LH
Calleja
Elizabeth
E
Trippett
Tanya
T
LaQuaglia
Michael
M
Huvos
Andrew G
AG
Gerald
William
W
Healey
John H
JH
Meyers
Paul A
PA
Gorlick
Richard
R
D000293:Adolescent; D000328:Adult; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001855:Bone Marrow Diseases / Q000139:chemically induced; D001859:Bone Neoplasms / Q000188:drug therapy; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003967:Diarrhea / Q000139:chemically induced; D004341:Drug Evaluation; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy; D008297:Male; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors*; D009369:Neoplasms / Q000188:drug therapy*; D018242:Neuroectodermal Tumors, Primitive / Q000188:drug therapy; D009519:New York City / Q000453:epidemiology; D012516:Osteosarcoma / Q000188:drug therapy; D012189:Retrospective Studies; D012208:Rhabdomyosarcoma / Q000188:drug therapy; D012512:Sarcoma, Ewing / Q000188:drug therapy; D059004:Topoisomerase I Inhibitors; D016896:Treatment Outcome
D000972:Antineoplastic Agents, Phytogenic; D004791:Enzyme Inhibitors; D009363:Neoplasm Proteins; D059004:Topoisomerase I Inhibitors; D000077146:Irinotecan; D002166:Camptothecin