Vincristine, actinomycin, and cyclophosphamide compared with vincristine, actinomycin, and cyclophosphamide alternating with vincristine, topotecan, and cyclophosphamide for intermediate-risk rhabdomyosarcoma: children's oncology group study D9803.
OBJECTIVE
The purpose of this study was to compare the outcome of patients with intermediate-risk rhabdomyosarcoma (RMS) treated with standard VAC (vincristine, dactinomycin, and cyclophosphamide) chemotherapy to that of patients treated with VAC alternating with vincristine, topotecan, and cyclophosphamide (VAC/VTC).


METHODS
Patients were randomly assigned to 39 weeks of VAC versus VAC/VTC; local therapy began after week 12. Patients with parameningeal RMS with intracranial extension (PME) were treated with VAC and immediate x-ray therapy. The primary study end point was failure-free survival (FFS). The study was designed with 80% power (5% two-sided alpha level) to detect an increase in 5-year FFS from 64% to 75% with VAC/VTC.


RESULTS
A total of 617 eligible patients were entered onto the study: 264 were randomly assigned to VAC and 252 to VAC/VTC; 101 PME patients were nonrandomly treated with VAC. Treatment strata were embryonal RMS, stage 2/3, group III (33%); embryonal RMS, group IV, less than age 10 years (7%); alveolar RMS or undifferentiated sarcoma (UDS), stage 1 or group I (17%); alveolar RMS/UDS (27%); and PME (16%). At a median follow-up of 4.3 years, 4-year FFS was 73% with VAC and 68% with VAC/VTC (P = .3). There was no difference in effect of VAC versus VAC/VTC across risk groups. The frequency of second malignancies was similar between the two treatment groups.


CONCLUSIONS
For intermediate-risk RMS, VAC/VTC does not significantly improve FFS compared with VAC.
Arndt
Carola A S
CA
Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN 55905, USA. carndt@mayo.edu
Stoner
Julie A
JA
Hawkins
Douglas S
DS
Rodeberg
David A
DA
Hayes-Jordan
Andrea A
AA
Paidas
Charles N
CN
Parham
David M
DM
Teot
Lisa A
LA
Wharam
Moody D
MD
Breneman
John C
JC
Donaldson
Sarah S
SS
Anderson
James R
JR
Meyer
William H
WH
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D003609:Dactinomycin / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D008297:Male; D009367:Neoplasm Staging; D012208:Rhabdomyosarcoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D019772:Topotecan / Q000008:administration & dosage / Q000009:adverse effects; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
D003609:Dactinomycin; D014750:Vincristine; D019772:Topotecan; D003520:Cyclophosphamide