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document
Results of the EICESS-92 Study : two randomized trials of Ewing 's sarcoma treatment -- cyclophosphamide compared with ifosfamide in standard-risk patients and assessment of benefit of etoposide added to standard treatment in high-risk patients . PURPOSE The European Intergroup Cooperative Ewing 's Sarcoma Study investigated whether cyclophosphamide has a similar efficacy as ifosfamide in standard-risk ( SR ) patients and whether the addition of etoposide improves survival in high-risk ( HR ) patients . PATIENTS AND METHODS SR patients ( localized tumors , volume < 100 mL ) were randomly assigned to receive four courses of vincristine , dactinomycin , ifosfamide , and doxorubicin ( VAIA ) induction therapy followed by 10 courses of either VAIA or vincristine , dactinomycin , cyclophosphamide , and doxorubicin ( VACA ; cyclophosphamide replacing ifosfamide ) . HR patients ( volume > or=100 mL or metastases ) were randomly assigned to receive 14 courses of either VAIA or VAIA plus etoposide ( EVAIA ) . Outcome measures were event-free survival ( EFS ; defined as the time to first recurrence , progression , second malignancy , or death ) and overall survival ( OS ) . RESULTS A total of 647 patients were randomly assigned : 79 SR patients were assigned to VAIA , 76 SR patients were assigned to VACA , 240 HR were assigned to VAIA , and 252 HR patients were assigned to EVAIA . The median follow-up was 8.5 years . In the SR group , the hazard ratios ( VACA v VAIA ) for EFS and OS were 0.91 ( 95 % CI , 0.55 to 1.53 ) and 1.08 ( 95 % CI , 0.58 to 2.03 ) , respectively . There was a higher incidence of hematologic toxicities in the VACA arm . In the HR group , the EFS and OS hazard ratios ( EVAIA v VAIA ) indicated a 17 % reduction in the risk of an event ( 95 % CI , -35 % to 5 % ; P = .12 ) and 15 % reduction in dying ( 95 % CI , -34 % to 10 % ) , respectively . The effect seemed greater among patients without metastases ( hazard ratio = 0.79 ; P = .16 ) than among those with metastases ( hazard ratio = 0.96 ; P = .84 ) . CONCLUSION Cyclophosphamide seemed to have a similar effect on EFS and OS as ifosfamide in SR patients but was associated with increased toxicity . In HR patients , the addition of etoposide seemed to be beneficial .
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Intervention_Pharmacological
cyclophosphamide
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Intervention_Pharmacological
ifosfamide
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Intervention_Pharmacological
etoposide
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Intervention_Pharmacological
cyclophosphamide
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Intervention_Pharmacological
ifosfamide
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Intervention_Pharmacological
etoposide
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Intervention_Pharmacological
vincristine , dactinomycin , ifosfamide , and doxorubicin ( VAIA ) induction therapy
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Intervention_Pharmacological
VAIA or vincristine , dactinomycin , cyclophosphamide , and doxorubicin
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Intervention_Pharmacological
VAIA
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Intervention_Pharmacological
VAIA
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Intervention_Pharmacological
etoposide ( EVAIA )
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Intervention_Pharmacological
VAIA
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Intervention_Pharmacological
VACA
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Intervention_Pharmacological
VAIA
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Intervention_Pharmacological
EVAIA
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Outcome_Mortality
survival
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Outcome_Mortality
event-free survival ( EFS
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Outcome_Mortality
overall survival ( OS ) .
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Outcome_Physical
hazard ratios
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Outcome_Physical
hematologic toxicities
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Outcome_Physical
EFS and OS hazard ratios
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Outcome_Physical
EFS and OS
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Outcome_Physical
toxicity