High-Dose Chemotherapy With Autologous Stem Cell Rescue

The role of high-dose therapy with busulfan-melphalan (BuMel) followed by stem cell rescue was investigated in the prospective randomized EURO-EWING-INTERGROUP-EE99 (NCT00020566) trial for two distinct groups:[33]The induction regimen employed in the EURO-EWING-INTERGROUP-EE99 trial included VIDE. This regimen is less dose intensive than the regimen employed in COG studies. This can be inferred from the intended dose intensity of the agents employed for the 21-week period that preceded randomization in the EURO-EWING-INTERGROUP-EE99 study (see Table 6). The lower dose intensity can also be inferred from the outcome of the EURO-EWING-INTERGROUP-EE99 study for patients in the localized disease stratum. Results from this study include the following: The observation that high-dose therapy with autologous stem cell rescue improved outcomes for patients with a poor response to initial therapy in the EURO-EWING-INTERGROUP-EE99 study must be interpreted in this context. The advantage of high-dose therapy as consolidation for patients with a poor response to initial treatment (with a less intensive regimen) cannot be extrapolated to a population of patients who received a more intensive treatment regimen as initial therapy.

The role of high-dose therapy with busulfan-melphalan (BuMel) followed by stem cell rescue was investigated in the prospective randomized EURO-EWING-INTERGROUP-EE99 (NCT00020566) trial for two distinct groups:[33]The induction regimen employed in the EURO-EWING-INTERGROUP-EE99 trial included VIDE. This regimen is less dose intensive than the regimen employed in COG studies. This can be inferred from the intended dose intensity of the agents employed for the 21-week period that preceded randomization in the EURO-EWING-INTERGROUP-EE99 study (see Table 6). The lower dose intensity can also be inferred from the outcome of the EURO-EWING-INTERGROUP-EE99 study for patients in the localized disease stratum. Results from this study include the following: The observation that high-dose therapy with autologous stem cell rescue improved outcomes for patients with a poor response to initial therapy in the EURO-EWING-INTERGROUP-EE99 study must be interpreted in this context. The advantage of high-dose therapy as consolidation for patients with a poor response to initial treatment (with a less intensive regimen) cannot be extrapolated to a population of patients who received a more intensive treatment regimen as initial therapy.

Patients who presented with isolated pulmonary metastases (R2pulm).

The role of high-dose therapy with busulfan-melphalan (BuMel) followed by stem cell rescue was investigated in the prospective randomized EURO-EWING-INTERGROUP-EE99 (NCT00020566) trial for two distinct groups:[33]The induction regimen employed in the EURO-EWING-INTERGROUP-EE99 trial included VIDE. This regimen is less dose intensive than the regimen employed in COG studies. This can be inferred from the intended dose intensity of the agents employed for the 21-week period that preceded randomization in the EURO-EWING-INTERGROUP-EE99 study (see Table 6). The lower dose intensity can also be inferred from the outcome of the EURO-EWING-INTERGROUP-EE99 study for patients in the localized disease stratum. Results from this study include the following: The observation that high-dose therapy with autologous stem cell rescue improved outcomes for patients with a poor response to initial therapy in the EURO-EWING-INTERGROUP-EE99 study must be interpreted in this context. The advantage of high-dose therapy as consolidation for patients with a poor response to initial treatment (with a less intensive regimen) cannot be extrapolated to a population of patients who received a more intensive treatment regimen as initial therapy.

Patients with localized tumors with poor response to initial chemotherapy (<90% necrosis) or with large tumors (>200 mL) (R2loc). Both study arms were compromised by the potential for selection bias for patients who were eligible for and accepted randomization, which may limit the generalizability of the results. Only 40% of eligible patients were randomized.

The role of high-dose therapy with busulfan-melphalan (BuMel) followed by stem cell rescue was investigated in the prospective randomized EURO-EWING-INTERGROUP-EE99 (NCT00020566) trial for two distinct groups:[33]The induction regimen employed in the EURO-EWING-INTERGROUP-EE99 trial included VIDE. This regimen is less dose intensive than the regimen employed in COG studies. This can be inferred from the intended dose intensity of the agents employed for the 21-week period that preceded randomization in the EURO-EWING-INTERGROUP-EE99 study (see Table 6). The lower dose intensity can also be inferred from the outcome of the EURO-EWING-INTERGROUP-EE99 study for patients in the localized disease stratum. Results from this study include the following: The observation that high-dose therapy with autologous stem cell rescue improved outcomes for patients with a poor response to initial therapy in the EURO-EWING-INTERGROUP-EE99 study must be interpreted in this context. The advantage of high-dose therapy as consolidation for patients with a poor response to initial treatment (with a less intensive regimen) cannot be extrapolated to a population of patients who received a more intensive treatment regimen as initial therapy. › Patients with localized tumors with poor response to initial chemotherapy (<90% necrosis) or with large tumors (>200 mL) (R2loc). Both study arms were compromised by the potential for selection bias for patients who were eligible for and accepted randomization, which may limit the generalizability of the results. Only 40% of eligible patients were randomized.

For R2pulm patients, there was no statistically significant difference in EFS or OS between the treatment groups.[34]

The role of high-dose therapy with busulfan-melphalan (BuMel) followed by stem cell rescue was investigated in the prospective randomized EURO-EWING-INTERGROUP-EE99 (NCT00020566) trial for two distinct groups:[33]The induction regimen employed in the EURO-EWING-INTERGROUP-EE99 trial included VIDE. This regimen is less dose intensive than the regimen employed in COG studies. This can be inferred from the intended dose intensity of the agents employed for the 21-week period that preceded randomization in the EURO-EWING-INTERGROUP-EE99 study (see Table 6). The lower dose intensity can also be inferred from the outcome of the EURO-EWING-INTERGROUP-EE99 study for patients in the localized disease stratum. Results from this study include the following: The observation that high-dose therapy with autologous stem cell rescue improved outcomes for patients with a poor response to initial therapy in the EURO-EWING-INTERGROUP-EE99 study must be interpreted in this context. The advantage of high-dose therapy as consolidation for patients with a poor response to initial treatment (with a less intensive regimen) cannot be extrapolated to a population of patients who received a more intensive treatment regimen as initial therapy. › Patients with localized tumors with poor response to initial chemotherapy (<90% necrosis) or with large tumors (>200 mL) (R2loc). Both study arms were compromised by the potential for selection bias for patients who were eligible for and accepted randomization, which may limit the generalizability of the results. Only 40% of eligible patients were randomized. › For R2pulm patients, there was no statistically significant difference in EFS or OS between the treatment groups.[34]

The EFS rates at 3 years were 50.6% for patients who received vincristine, dactinomycin, and ifosfamide (VAI) plus whole-lung irradiation versus 56.6% for patients who received BuMel.

The role of high-dose therapy with busulfan-melphalan (BuMel) followed by stem cell rescue was investigated in the prospective randomized EURO-EWING-INTERGROUP-EE99 (NCT00020566) trial for two distinct groups:[33]The induction regimen employed in the EURO-EWING-INTERGROUP-EE99 trial included VIDE. This regimen is less dose intensive than the regimen employed in COG studies. This can be inferred from the intended dose intensity of the agents employed for the 21-week period that preceded randomization in the EURO-EWING-INTERGROUP-EE99 study (see Table 6). The lower dose intensity can also be inferred from the outcome of the EURO-EWING-INTERGROUP-EE99 study for patients in the localized disease stratum. Results from this study include the following: The observation that high-dose therapy with autologous stem cell rescue improved outcomes for patients with a poor response to initial therapy in the EURO-EWING-INTERGROUP-EE99 study must be interpreted in this context. The advantage of high-dose therapy as consolidation for patients with a poor response to initial treatment (with a less intensive regimen) cannot be extrapolated to a population of patients who received a more intensive treatment regimen as initial therapy. › Patients with localized tumors with poor response to initial chemotherapy (<90% necrosis) or with large tumors (>200 mL) (R2loc). Both study arms were compromised by the potential for selection bias for patients who were eligible for and accepted randomization, which may limit the generalizability of the results. Only 40% of eligible patients were randomized. › For R2pulm patients, there was no statistically significant difference in EFS or OS between the treatment groups.[34]

The EFS rates at 8 years were 43.1% for patients who received VAI plus whole-lung irradiation versus 52.9% for patients who received BuMel.

The role of high-dose therapy with busulfan-melphalan (BuMel) followed by stem cell rescue was investigated in the prospective randomized EURO-EWING-INTERGROUP-EE99 (NCT00020566) trial for two distinct groups:[33]The induction regimen employed in the EURO-EWING-INTERGROUP-EE99 trial included VIDE. This regimen is less dose intensive than the regimen employed in COG studies. This can be inferred from the intended dose intensity of the agents employed for the 21-week period that preceded randomization in the EURO-EWING-INTERGROUP-EE99 study (see Table 6). The lower dose intensity can also be inferred from the outcome of the EURO-EWING-INTERGROUP-EE99 study for patients in the localized disease stratum. Results from this study include the following: The observation that high-dose therapy with autologous stem cell rescue improved outcomes for patients with a poor response to initial therapy in the EURO-EWING-INTERGROUP-EE99 study must be interpreted in this context. The advantage of high-dose therapy as consolidation for patients with a poor response to initial treatment (with a less intensive regimen) cannot be extrapolated to a population of patients who received a more intensive treatment regimen as initial therapy. › Patients with localized tumors with poor response to initial chemotherapy (<90% necrosis) or with large tumors (>200 mL) (R2loc). Both study arms were compromised by the potential for selection bias for patients who were eligible for and accepted randomization, which may limit the generalizability of the results. Only 40% of eligible patients were randomized. › For R2pulm patients, there was no statistically significant difference in EFS or OS between the treatment groups.[34]

The OS rates at 3 years were 68.0% for patients who received VAI plus whole-lung irradiation versus 68.2% for patients who received BuMel.

The role of high-dose therapy with busulfan-melphalan (BuMel) followed by stem cell rescue was investigated in the prospective randomized EURO-EWING-INTERGROUP-EE99 (NCT00020566) trial for two distinct groups:[33]The induction regimen employed in the EURO-EWING-INTERGROUP-EE99 trial included VIDE. This regimen is less dose intensive than the regimen employed in COG studies. This can be inferred from the intended dose intensity of the agents employed for the 21-week period that preceded randomization in the EURO-EWING-INTERGROUP-EE99 study (see Table 6). The lower dose intensity can also be inferred from the outcome of the EURO-EWING-INTERGROUP-EE99 study for patients in the localized disease stratum. Results from this study include the following: The observation that high-dose therapy with autologous stem cell rescue improved outcomes for patients with a poor response to initial therapy in the EURO-EWING-INTERGROUP-EE99 study must be interpreted in this context. The advantage of high-dose therapy as consolidation for patients with a poor response to initial treatment (with a less intensive regimen) cannot be extrapolated to a population of patients who received a more intensive treatment regimen as initial therapy. › Patients with localized tumors with poor response to initial chemotherapy (<90% necrosis) or with large tumors (>200 mL) (R2loc). Both study arms were compromised by the potential for selection bias for patients who were eligible for and accepted randomization, which may limit the generalizability of the results. Only 40% of eligible patients were randomized. › For R2pulm patients, there was no statistically significant difference in EFS or OS between the treatment groups.[34]

The OS rates at 8 years were 54.2% for patients who received VAI plus whole-lung irradiation versus 55.3% for patients who received BuMel.

The role of high-dose therapy with busulfan-melphalan (BuMel) followed by stem cell rescue was investigated in the prospective randomized EURO-EWING-INTERGROUP-EE99 (NCT00020566) trial for two distinct groups:[33]The induction regimen employed in the EURO-EWING-INTERGROUP-EE99 trial included VIDE. This regimen is less dose intensive than the regimen employed in COG studies. This can be inferred from the intended dose intensity of the agents employed for the 21-week period that preceded randomization in the EURO-EWING-INTERGROUP-EE99 study (see Table 6). The lower dose intensity can also be inferred from the outcome of the EURO-EWING-INTERGROUP-EE99 study for patients in the localized disease stratum. Results from this study include the following: The observation that high-dose therapy with autologous stem cell rescue improved outcomes for patients with a poor response to initial therapy in the EURO-EWING-INTERGROUP-EE99 study must be interpreted in this context. The advantage of high-dose therapy as consolidation for patients with a poor response to initial treatment (with a less intensive regimen) cannot be extrapolated to a population of patients who received a more intensive treatment regimen as initial therapy. › Patients with localized tumors with poor response to initial chemotherapy (<90% necrosis) or with large tumors (>200 mL) (R2loc). Both study arms were compromised by the potential for selection bias for patients who were eligible for and accepted randomization, which may limit the generalizability of the results. Only 40% of eligible patients were randomized.

Among R2loc patients, the 3-year EFS rate was superior with BuMel compared with continued chemotherapy (66.9% vs. 53.1%; P = .019). The 3-year OS rate was 78.0% with BuMel and 72.2% with continued chemotherapy (P = .028).[33]

The role of high-dose therapy with busulfan-melphalan (BuMel) followed by stem cell rescue was investigated in the prospective randomized EURO-EWING-INTERGROUP-EE99 (NCT00020566) trial for two distinct groups:[33]The induction regimen employed in the EURO-EWING-INTERGROUP-EE99 trial included VIDE. This regimen is less dose intensive than the regimen employed in COG studies. This can be inferred from the intended dose intensity of the agents employed for the 21-week period that preceded randomization in the EURO-EWING-INTERGROUP-EE99 study (see Table 6). The lower dose intensity can also be inferred from the outcome of the EURO-EWING-INTERGROUP-EE99 study for patients in the localized disease stratum. Results from this study include the following: The observation that high-dose therapy with autologous stem cell rescue improved outcomes for patients with a poor response to initial therapy in the EURO-EWING-INTERGROUP-EE99 study must be interpreted in this context. The advantage of high-dose therapy as consolidation for patients with a poor response to initial treatment (with a less intensive regimen) cannot be extrapolated to a population of patients who received a more intensive treatment regimen as initial therapy.

Patients assigned to the most favorable risk stratum, R1, were patients with small primary tumors, less than 200 mL in volume. In addition, patients who had poor response to the initial six cycles of therapy with VIDE, as assessed by pathology or radiology, were removed from the R1 stratum and assigned to the R2 stratum. As a result, the R1 stratum includes only patients with small primary tumors and favorable response to initial therapy.[35]

The role of high-dose therapy with busulfan-melphalan (BuMel) followed by stem cell rescue was investigated in the prospective randomized EURO-EWING-INTERGROUP-EE99 (NCT00020566) trial for two distinct groups:[33]The induction regimen employed in the EURO-EWING-INTERGROUP-EE99 trial included VIDE. This regimen is less dose intensive than the regimen employed in COG studies. This can be inferred from the intended dose intensity of the agents employed for the 21-week period that preceded randomization in the EURO-EWING-INTERGROUP-EE99 study (see Table 6). The lower dose intensity can also be inferred from the outcome of the EURO-EWING-INTERGROUP-EE99 study for patients in the localized disease stratum. Results from this study include the following: The observation that high-dose therapy with autologous stem cell rescue improved outcomes for patients with a poor response to initial therapy in the EURO-EWING-INTERGROUP-EE99 study must be interpreted in this context. The advantage of high-dose therapy as consolidation for patients with a poor response to initial treatment (with a less intensive regimen) cannot be extrapolated to a population of patients who received a more intensive treatment regimen as initial therapy. › Patients assigned to the most favorable risk stratum, R1, were patients with small primary tumors, less than 200 mL in volume. In addition, patients who had poor response to the initial six cycles of therapy with VIDE, as assessed by pathology or radiology, were removed from the R1 stratum and assigned to the R2 stratum. As a result, the R1 stratum includes only patients with small primary tumors and favorable response to initial therapy.[35]

The probability for EFS at 3 years for this favorable group was 76%, and the OS rate at 3 years was 85%.

The role of high-dose therapy with busulfan-melphalan (BuMel) followed by stem cell rescue was investigated in the prospective randomized EURO-EWING-INTERGROUP-EE99 (NCT00020566) trial for two distinct groups:[33]The induction regimen employed in the EURO-EWING-INTERGROUP-EE99 trial included VIDE. This regimen is less dose intensive than the regimen employed in COG studies. This can be inferred from the intended dose intensity of the agents employed for the 21-week period that preceded randomization in the EURO-EWING-INTERGROUP-EE99 study (see Table 6). The lower dose intensity can also be inferred from the outcome of the EURO-EWING-INTERGROUP-EE99 study for patients in the localized disease stratum. Results from this study include the following: The observation that high-dose therapy with autologous stem cell rescue improved outcomes for patients with a poor response to initial therapy in the EURO-EWING-INTERGROUP-EE99 study must be interpreted in this context. The advantage of high-dose therapy as consolidation for patients with a poor response to initial treatment (with a less intensive regimen) cannot be extrapolated to a population of patients who received a more intensive treatment regimen as initial therapy.

For all patients with localized Ewing sarcoma, including patients with large primary tumors and patients with poor response to initial therapy treated on the COG-AEWS1031 (NCT01231906) trial, the 5-year probability for EFS was 73%, and the 5-year OS rate was 88%.[10]