Outcome of patients with recurrent medulloblastoma or central nervous system germinoma treated with low dose continuous intravenous etoposide along with dose‐intensive chemotherapy followed by autologous hematopoietic stem cell rescue

Grodman, H.; Wolfe, Lawrence C.; Kretschmar, Cynthia S.

doi:10.1002/pbc.21985

Cited by 14 publications

(11 citation statements)

References 21 publications

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“…The observation of the good response rate to metronomic [19,20] or conventional chemotherapy in this study suggests a future relapse study to contain an initial conventional chemotherapy, the utilization of all local treatment options and oral maintenance chemotherapy. Whether some specific group of patients will profit by an intensified chemotherapeutic approach, has to be further evaluated.…”

Section: Discussionmentioning

confidence: 88%

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Treatment of recurrent primitive neuroectodermal tumors (PNET) in children and adolescents with high-dose chemotherapy (HDC) and stem cell support: results of the HITREZ 97 multicentre trial

et al. 2014

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Early studies with high-dose chemotherapy for treatment of relapsed cerebral PNET had shown modest efficacy but considerable toxicity. The HIT97 national trial tested a nonrandomized but stratified relapse protocol using either intensive chemotherapy, potentially high dose, or oral chemotherapy. 72 patients (59 disseminated) whose primary treatment had been surgery (97 %), radiotherapy (88 %), and/or chemotherapy (95 %) were enrolled in the intensive chemotherapy arm at diagnosis of relapse or resistance. As a window for this study they received two courses of a 96-hour infusion with carboplatin and etoposide. A response (complete or partial remission) was documented by MRI. Responders received two more cycles of this therapy and stem cell collection, before they received HDC (carboplatin, etoposide, thiotepa) and stem cell support. All possibilities of local therapy were to be explored and applied. After two courses of chemotherapy there was a 52 % response rate (41/72 patients). The median PFS and OS for all 72 patients were 11.6 and 21.1 months. Patients with medulloblastoma had a longer PFS and OS (12.6 and 22.6 months) than those with other PNETs (3.1 and 12.3 months). Favourable prognostic features were no new signs of clinical impairment and localised disease at relapse diagnosis. For the 27 patients who received HDC the median PFS and OS were 8.4 and 20.2 months, respectively. HDC did not benefit patients with resistant cerebral PNET and was associated with profound haematological and mucosal toxicity (90-100 % grade III, IV), infections (50 % grade III and IV) and severe ototoxicity (50 % grade III, 12.5 % grade IV). Treatment related mortality was 8 %. There was low long-term survival and only 2/72 patients are in continuous remission. Adding HDC in patients who responded to the initial courses of chemotherapy did not improve survival. Patients with relapsed cerebral PNET who respond to conventional chemotherapy do not profit from further augmentation to HDC.

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Section: Discussionmentioning

confidence: 88%

“…Other authors had described a promising role of highdose chemotherapy in treating relapsed brain tumor patients [13][14][15][16][17][18][19][20][21][22][23]. The selectivity and heterogeneity of their patients and of their treatment should be considered.…”

Section: Discussionmentioning

confidence: 96%

Treatment of recurrent primitive neuroectodermal tumors (PNET) in children and adolescents with high-dose chemotherapy (HDC) and stem cell support: results of the HITREZ 97 multicentre trial

et al. 2014

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“…The prognosis remains dismal for patients who experience disease progression. The expected 2‐year overall survival (OS) after disease progression is less than 25% . Management of these patients has been a challenge as there is no standard approach to salvage therapy …”

Section: Introductionmentioning

confidence: 99%

Reirradiation of recurrent medulloblastoma: Does clinical benefit outweigh risk for toxicity?

Wetmore

Herington

Lin

et al. 2014

Cancer

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Purpose Patients with recurrent medulloblastoma (MB) have a dismal prognosis. There has been a reluctance to use radiation in the salvage therapy regimens for these patients because of concerns about toxicity and unknown efficacy. Comparing survival outcomes and toxicities in relapsed patients treated with and without radiation may help define its role. Methods and Materials A retrospective review was conducted that included 38 patients with recurrent MB treated with similar risk-adapted therapy at initial diagnosis; re-irradiation was a component of salvage therapy in 14. Overall survival (OS) and toxicity were evaluated according to the use of radiation, prior risk stratification and other factors. Results For relapsed standard risk patients, the use of additional irradiation resulted in a statistically significant improvement in OS from initial diagnosis (p=0.036) where 5- and 10-year OS rates were 55% ± 14% vs. 33% ± 16% and 46% ± 14% vs. 0%, respectively for re-irradiated patients vs. others. A similar improvement was observed in high risk (p=0.003) patients. There was an association between the use of additional irradiation and an increased rate of necrosis as determined by neuroimaging (p=0.0468). Conclusion The use of irradiation as a component of salvage therapy for relapsed MB may prolong survival. The benefit appears to be greatest for relapsed standard risk patients.

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“…Two-year survival rates for relapsed medulloblastoma were reported to be below 20% (8). Recently, sequential cycles of dose-intensive chemotherapy or tandem transplantation have been tried in the treatment of chemo-sensitive high-risk or recurrent brain tumors, including recurrent medulloblastoma (9-11).…”

Section: Discussionmentioning

confidence: 99%

“…The survival rate was reported as a broad range, 5-54%, by studies done in various different situations with regard to pre-transplant conventional chemotherapy, conditioning regimens, disease status prior to HDCT, and adjuvant therapy. Some studies did not separate recurrent medulloblastoma from high-risk medulloblastoma or other brain tumors types in their study group (8, 12). Grururangan et al (13) reported a 3-yr overall survival rate of 14% in recurrent medulloblastoma patients who underwent HDCT/ASCT and received no irradiation before relapse, while no survival was found in those who underwent HDCT/ASCT receiving irradiation before relapse and in those who did not undergo HDCT/ASCT and received only standard SC.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of High-dose Chemotherapy and Autologous Stem Cell Transplantation in Patients with Relapsed Medulloblastoma: A Report on The Korean Society for Pediatric Neuro-Oncology (KSPNO)-S-053 Study

et al. 2010

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The efficacy and toxicity of high-dose chemotherapy and autologous stem cell transplantation (HDCT/ASCT) were investigated for improving the outcomes of patients with relapsed medulloblastoma. A total of 15 patients with relapsed medulloblastoma were enrolled in the KSPNO-S-053 study from May 2005 to May 2007. All patients received approximately 4 cycles of salvage chemotherapy after relapse. Thirteen underwent HDCT/ASCT; CTE and CM regimen were employed for the first HDCT (HDCT1) and second HDCT (HDCT2), respectively, and 7 underwent HDCT2. One transplant related mortality (TRM) due to veno-occlusive disease (VOD) occurred during HDCT1 but HDCT2 was tolerable with no further TRM. The 3-yr overall survival probability and event-free survival rates ±95% confidence intervals (CI) were 33.3±12.2% and 26.7% ±11.4%, respectively. When analysis was confined to only patients who had a complete response (CR) or partial response (PR) prior to HDCT, the probability of 3-yr overall survival rates ±95% CI was 40.0±15.5%. No patients with stable disease (SD) or progressive disease (PD) survived. Survival rates from protocol KSPNO-S-053 are encouraging and show that tumor status prior to HDCT/ASCT is an important factor to consider for improving survival rates of patients with relapsed medulloblastoma.

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Outcome of patients with recurrent medulloblastoma or central nervous system germinoma treated with low dose continuous intravenous etoposide along with dose‐intensive chemotherapy followed by autologous hematopoietic stem cell rescue

Cited by 14 publications

References 21 publications

Treatment of recurrent primitive neuroectodermal tumors (PNET) in children and adolescents with high-dose chemotherapy (HDC) and stem cell support: results of the HITREZ 97 multicentre trial

Treatment of recurrent primitive neuroectodermal tumors (PNET) in children and adolescents with high-dose chemotherapy (HDC) and stem cell support: results of the HITREZ 97 multicentre trial

Reirradiation of recurrent medulloblastoma: Does clinical benefit outweigh risk for toxicity?

Efficacy of High-dose Chemotherapy and Autologous Stem Cell Transplantation in Patients with Relapsed Medulloblastoma: A Report on The Korean Society for Pediatric Neuro-Oncology (KSPNO)-S-053 Study

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