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SIOP MMT 95: Intensified
(6 drug) versus standard (IVA) chemotherapy for high risk non metastatic
rhabdomyosarcoma (RMS)
M. Stevens, A. Rey, N. Bouvet, C. Ellershaw, J. Sanchez de Toledo, O. Oberlin
University of Bristol, Bristol, United Kingdom; Institut Gustave
Roussy, Villejuif, France; United Kingdom Children's Cancer Study Group,
Leicester, United Kingdom; Hospital Materno Infantil, Vall d'Hebron, Barcelona,
Spain.
Background. MMT 95 was 3rd in a series of SIOP
collaborations for children with non metastatic STS.
Principal study objectives were: low and standard risk patients, to
maintain excellent survival with limited chemotherapy and very selective use of
local therapy; high risk patients, to explore survival advantage for an
intensified chemotherapy strategy in a randomised trial.
Methods. Eligibility for randomisation included age ≥ 6
months ≤18 years, no distant metastases, diagnosis within previous 8 weeks
without prior treatment except surgery, pathology available for central review,
written consent according to institutional requirement.
From July 1995 to July 2003, 456 high risk patients (incompletely
resected embryonal RMS, undifferentiated sarcoma and soft tissue PNET at all
sites except paratesticular, vagina and uterus, and all alveolar RMS) were
randomised to receive IVA (ifosfamide, vincristine, actinomycin D) or a 6 drug
combination (IVA + carboplatin, epirubicin, etoposide) both delivered over 27
weeks.
Cumulative dose / m2 = ifosfamide 54g (both arms), epirubicin
450 mg, etoposide 1350 mg (6 drug).
Delivery of radiotherapy was determined according to site and / or
response to chemotherapy ± surgery.
Non randomised exceptions were: orbital tumours (allocated IVA); SIOP
stage III (node positive) and young (age < 3yr) parameningeal tumours
(allocated 6 drugs).
The study was powered to detect 10% difference in 3 year OS.
Results. Data given only for randomised patients
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3 yr OS (%)
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3 yr EFS (%)
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IVA
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6 drug
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p-value
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IVA
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6 drug
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p-value
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All patients
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81
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79
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ns
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65
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63
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ns
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eRMS
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86
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84
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ns
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73
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70
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ns
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aRMS
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83
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69
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ns
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58
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42
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ns
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Toxicity was significantly greater (infection,
myelosuppression, mucositis) for the 6 drug arm.
Conclusions. Intensification of chemotherapy provides no overall
advantage for non metastatic RMS / other chemosensitive STS, and adds
toxicity.
Further follow up is required to identify any benefit for patient
subgroups.
Copyright 2004 American Society of Clinical Oncology All rights
reserved worldwide.
Source: http://www.asco.org/ac/1,1003,_12-002636-00_18-0026-00_19-001438,00.asp
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