Up-front window trial of topotecan in previously untreated children and adolescents with metastatic rhabdomyosarcoma: an intergroup rhabdomyosarcoma study.
OBJECTIVE
To investigate the antitumor activity and toxicity of topotecan, used alone and in combination with conventional therapy, in patients with metastatic rhabdomyosarcoma (RMS).


METHODS
Forty-eight patients younger than 21 years of age with newly diagnosed metastatic RMS received 2.0 to 2.4 mg/m(2) of topotecan intravenously daily for 5 days every 21 days before standard therapy. Two courses were given in the absence of progressive disease or excessive toxicity and response was assessed. Patients with at least a partial response (PR) to topotecan proceeded to therapy with alternating courses of vincristine 1.5 mg/m(2), dactinomycin 1.5 mg/m(2), and cyclophosphamide 2.2 g/m(2) (VAC) and vincristine 1.5 mg/m(2), topotecan 0.75 mg/m(2) daily x 5, and cyclophosphamide 250 mg/m(2) daily x 5. Patients who did not respond to topotecan received continuation therapy with VAC alone.


RESULTS
The overall response rate to topotecan was 46% (complete response, 4%; partial response 42%). Unexpectedly, patients with alveolar RMS had a higher rate of response (65%) than those with embryonal RMS (28%; P: = .08). The most common grade 3 or 4 toxicities were neutropenia (67%), anemia (33%), thrombocytopenia (25%), and infection (21%). Two-year failure-free survival and survival estimates were 24% and 46%, respectively. Response to window therapy did not correlate with survival.


CONCLUSIONS
The high response rate and acceptable toxicity profile of topotecan in children with advanced RMS support further evaluation of this agent in phase III trials. The superior responses in alveolar RMS are of interest.
Pappo
A S
AS
Intergroup Rhabdomyosarcoma Study Group representing the Children's Cancer Group, Arcadia, CA 91066-6012, USA.
Lyden
E
E
Breneman
J
J
Wiener
E
E
Teot
L
L
Meza
J
J
Crist
W
W
Vietti
T
T
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D012208:Rhabdomyosarcoma / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary*; D018232:Rhabdomyosarcoma, Alveolar / Q000188:drug therapy / Q000401:mortality / Q000556:secondary; D018233:Rhabdomyosarcoma, Embryonal / Q000188:drug therapy / Q000401:mortality / Q000556:secondary; D015996:Survival Rate; D019772:Topotecan / Q000009:adverse effects / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D019772:Topotecan