Effectiveness of ifosfamide (IFO) alone and in combination with cisplatinum (DDP) in patients with recurrent ewing's sarcoma

Göbel, Verena; Jürgens, Heribert; Etspüler, G.; Exner, Ulrich; Kühl, Joachim; Ritter, J; Winkler, Kurt; Göbel, U.

doi:10.1007/bf02579891

Cited by 3 publications

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“…Prolonged disease-free survival is achieved in the majority of patients with localized ES after treatment with multiagent chemotherapy and primary tumor control. [1][2][3][4] Larger initial tumor volume is a well-defined adverse prognostic factor, [5][6][7][8] the predictive power of which is over-ridden by the extent of histologically determined chemotherapy-induced necrosis assessed in resected primary tumors. 4,[8][9][10][11] These observations can be used to define subgroups of patients with localized ES in whom treatment interventions to improve survival may be examined.…”

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confidence: 99%

High-Dose Chemotherapy and Blood Autologous Stem-Cell Rescue Compared With Standard Chemotherapy in Localized High-Risk Ewing Sarcoma: Results of Euro-E.W.I.N.G.99 and Ewing-2008

Whelan

Deley

Dirksen

et al. 2018

JCO

122

102

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Purpose For over 30 years, the place of consolidation high-dose chemotherapy in Ewing sarcoma (ES) has been controversial. A randomized study was conducted to determine whether consolidation high-dose chemotherapy improved survival in patients with localized ES at high risk for relapse. Methods Randomization between busulfan and melphalan (BuMel) or standard chemotherapy (vincristine, dactinomycin, and ifosfamide [VAI], seven courses) was offered to patients if they were younger than 50 years of age with poor histologic response (≥ 10% viable cells) after receiving vincristine, ifosfamide, doxorubicin, and etoposide (six courses); or had a tumor volume at diagnosis ≥ 200 mL if unresected, or initially resected, or resected after radiotherapy. A 15% improvement in 3-year event-free survival (EFS) was sought (hazard ratio [HR], 0.60). Results Between 2000 and 2015, 240 patients classified as high risk (median age, 17.1 years) were randomly assigned to VAI (n = 118) or BuMel (n = 122). Seventy-eight percent entered the trial because of poor histologic response after chemotherapy alone. Median follow-up was 7.8 years. In an intent-to-treat analysis, the risk of event was significantly decreased by BuMel compared with VAI: HR, 0.64 (95% CI, 0.43 to 0.95; P = .026); 3- and 8-year EFS were, respectively, 69.0% (95% CI, 60.2% to 76.6%) versus 56.7% (95% CI, 47.6% to 65.4%) and 60.7% (95% CI, 51.1% to 69.6%) versus 47.1% (95% CI, 37.7% to 56.8%). Overall survival (OS) also favored BuMel: HR, 0.63 (95% CI, 0.41 to 0.95; P = .028); 3- and 8-year OS were, respectively, 78.0% (95% CI, 69.6% to 84.5%) versus 72.2% (95% CI, 63.3% to 79.6%) and 64.5% (95% CI, 54.4% to 73.5%) versus 55.6% (95% CI, 45.8% to 65.1%). Results were consistent in the sensitivity analysis. Two patients died as a result of BuMel-related toxicity, one after standard chemotherapy. Significantly more BuMel patients experienced severe acute toxicities from this course of chemotherapy compared with multiple VAI courses. Conclusion BuMel improved EFS and OS when given after vincristine, ifosfamide, doxorubicin, and etoposide induction in localized ES with predefined high-risk factors. For this group of patients, BuMel may be an important addition to the standard of care.

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confidence: 99%

High-Dose Chemotherapy and Blood Autologous Stem-Cell Rescue Compared With Standard Chemotherapy in Localized High-Risk Ewing Sarcoma: Results of Euro-E.W.I.N.G.99 and Ewing-2008

Whelan

Deley

Dirksen

et al. 2018

JCO

122

102

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“…In addition, male gender and increasing tumour volume were identified as possible indicators of poor outcome. Treatment strategies including doxorubicin (Nesbit et al, 1981), vincristine, doxorubicin, cyclophosphamide and actinomycin-D (Rosen et al, 1974) and ifosfamide (Demeocq et al, 1984;Bramwell et al, 1985;Gobel et al, 1986;Magrath et al, 1986) were suggested as regimens that could result in a higher response rate for patients with Ewing's tumour.…”

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Establishing long-term survival and cure in young patients with Ewing's sarcoma

et al. 2004

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This paper investigates the potential for long-term survivorship for young patients diagnosed with Ewing's sarcoma. Data are examined from two successive UKCCSG Ewing's Tumour studies (ET-1 and ET-2). Patients have been followed for up to 20 years. These studies had suggested that better 5-year survival with ET-2 over the earlier ET-1 was achieved by replacing cyclophosphamide by ifosfamide and increasing the dose of doxorubicin in a four-drug chemotherapy regimen. The updated hazard ratio, stratified for metastatic status at diagnosis, of 0.39 (95% confidence interval 0.12 -0.61) confirmed the advantage of the ET-2 regimen in terms of overall survival. Cure models, based on the Weibull distribution, suggested that factors for long-term survival in addition to presence of metastases were age, primary site of tumour and study. Modelling identified the proportion cured with the ET-2 protocol as best at 70% in those who are under 10 years with a nonpelvic primary site and without metastatic disease. This contrasts to only 13% cure in those with the corresponding adverse prognostic indicators. Additionally, the risk of death remains greatest but relatively constant over the first 2 years postdiagnosis, and then declines to a lower but constant value for the next 3 years before reaching the 'cure plateau' at about 5 years. This investigation suggests that 'cure' is possible for patients with Ewing's sarcoma. This is established at approximately 5 years post diagnosis and the proportion cured depends on the presence of metastases, pelvic site and age at diagnosis.

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The German Pediatric Oncology (GPO) Cooperative Study on Ewing’s Sarcoma

Winkler

Juêrgens

1988

Recent Concepts in Sarcoma Treatment

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Effectiveness of ifosfamide (IFO) alone and in combination with cisplatinum (DDP) in patients with recurrent ewing's sarcoma

Cited by 3 publications

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High-Dose Chemotherapy and Blood Autologous Stem-Cell Rescue Compared With Standard Chemotherapy in Localized High-Risk Ewing Sarcoma: Results of Euro-E.W.I.N.G.99 and Ewing-2008

High-Dose Chemotherapy and Blood Autologous Stem-Cell Rescue Compared With Standard Chemotherapy in Localized High-Risk Ewing Sarcoma: Results of Euro-E.W.I.N.G.99 and Ewing-2008

Establishing long-term survival and cure in young patients with Ewing's sarcoma

The German Pediatric Oncology (GPO) Cooperative Study on Ewing’s Sarcoma

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