Response of recurrent medulloblastoma to low-dose oral etoposide.

Ashley, David M.; Meier, Lisa; Kerby, Tracy; Zalduondo, Fernando M.; Friedman, Henry S.; Gajjar, Amar; Kun, Larry E.; Duffner, Patricia K.; Smith, Sharon H.; Longee, Darryl C.

doi:10.1200/jco.1996.14.6.1922

Cited by 125 publications

(63 citation statements)

References 9 publications

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“…This is an improvement in comparison to response rates ranging from 40 to 75% with conventional chemotherapy. [2][3][4][5][6][7][8][9] Among patients who had a second recurrence, we report an even longer median time to relapse post high-dose chemotherapy as compared to Dunkel et al (13.5 vs 7 months), with two patients surviving with stable disease. It is interesting to note that patients with metastatic disease (>M0) had a comparable median time to relapse as compared to those with no metastatic disease (16 vs 13 months).…”

Section: Discussionmentioning

confidence: 54%

“…1 Currently, there is no generally acceptable therapy for tumor recurrences. The most active chemotherapeutic agents include cisplatin or carboplatin, 2-4 lowdose oral etoposide, 5 PCV (procarbazine, CCNU, vincristine), 6 MOPP (nitrogen mustard, vincristine, procarbazine, prednisone), 7 and intraventricular and intrathecal therapy with Ara-C, methotrexate and thiotepa. 8 Despite reasonably high response rates of 40-75% with these agents, no long-term disease-free survival has been reported.…”

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confidence: 99%

“…8 Despite reasonably high response rates of 40-75% with these agents, no long-term disease-free survival has been reported. [1][2][3][4][5][6][7][8][9] Given that these agents are amenable to substantial dose-escalation, evaluation of high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) has been suggested. 9 Promising results with HDCT/ASCT prompted us to use this form of therapy for young adults with recurrent medulloblastoma, who were otherwise healthy and had no possibility of cure with conventional dose therapy.…”

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confidence: 99%

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Possible benefits of high-dose chemotherapy and autologous stem cell transplantation for adults with recurrent medulloblastoma

Zia

Chaudhry

Russell

et al. 2002

Bone Marrow Transplant

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Summary:In an attempt to improve the dismal prognosis of adults with recurrent medulloblastoma, six patients were treated with aggressive salvage therapy including highdose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT). At relapse, all patients underwent surgical debulking followed by HDCT/ASCT and then radiotherapy when possible. The treatment plan included two cycles of HDCT/ASCT; first with cyclophosphamide, etoposide and carboplatin (CECb) and then 2 months later with cyclophosphamide and thiotepa (CT). Three of the six patients received the planned therapy. One patient experienced severe toxicity requiring life-sustaining therapy. This patient developed multi-organ dysfunction including multiple enhancing lesions in both cerebral hemispheres that slowly resolved over several months. Two other patients did not mobilize sufficient stem cells for two ASCT procedures. They received one ASCT conditioned with cyclophosphamide, thiotepa and carboplatin (CTCb). Three of six patients had a complete response (CR); the other three had a partial response (PR). Following the first ASCT, median duration of response was 13.5 months (range 9-29 months) and median survival was 21.5 months (range 12-42 months). There was no treatment-related mortality. We conclude that HDCT/ASCT with CECb-CT or CTCb is active against recurrent medulloblastoma in adults and may be associated with prolonged remissions. Multiple enhancing cerebral lesions on brain MRI early post-HDCT/ASCT may be a consequence of the treatment rather than metastatic disease.

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Section: Discussionmentioning

confidence: 54%

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confidence: 99%

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confidence: 99%

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Possible benefits of high-dose chemotherapy and autologous stem cell transplantation for adults with recurrent medulloblastoma

Zia

Chaudhry

Russell

et al. 2002

Bone Marrow Transplant

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“…Recurrent medulloblastoma has a dismal prognosis (18)(19)(20)(21)(22)(23)(24). Therefore, the distinction between radiographic changes related to normal tissue damage by chemoradiotherapy and true disease progression affects the patient's subsequent treatment and prognosis.…”

Section: Resultsmentioning

confidence: 99%

Changes Mimicking New Leptomeningeal Disease After Intensity-Modulated Radiotherapy for Medulloblastoma

Muscal

Jones

Paulino

et al. 2009

International Journal of Radiation Oncology*Biology*Physics

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Purpose-Acute and late changes in magnetic resonance imaging of the pediatric brain have been described after radiotherapy (RT). We report the post-RT neuroimaging changes in the posterior fossa after intensity-modulated RT (IMRT) in children with medulloblastoma and contrast them with those of leptomeningeal disease.Methods and Materials-We performed a retrospective review of 53 consecutive children with medulloblastoma who were treated with craniospinal RT followed by IMRT to the posterior fossa and chemotherapy between 1997 and 2006.Results-After IMRT to the posterior fossa, 8 (15%) of 53 patients developed increased fluidattenuated inversion-recovery signal changes in the brainstem or cerebellum and patchy, multifocal, nodular contrast enhancement at a median of 6 months. The enhancement superficially resembled leptomeningeal disease. However, the enhancement resolved without intervention at a median of 6 months later. The accompanying fluid-attenuated inversion-recovery signal changes occasionally preceded the enhancement, were often parenchymal in location, and resolved or persisted to a lesser degree. All 8 patients with transient magnetic resonance imaging changes in the posterior fossa were alive at last follow-up. In contrast, leptomeningeal disease occurred in 8 (15%) of our 53 patients at a median of 19.5 months after IMRT completion. Of these 8 patients, 7 demonstrated initial nodular enhancement outside the conformal field, and 7 patients died.Conclusion-Magnetic resonance imaging changes can occur in the posterior fossa of children treated with IMRT for medulloblastoma. In our experience, these transient changes occur at a characteristic time and location after RT, allowing them to be distinguished from leptomeningeal disease.

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“…High-dose chemotherapy still remains an experimental procedure that has yet to be shown to have any benefit over conventional chemotherapy in relapsing patients. Scheduling that exposes tumour to more sustained levels of chemotherapy might be of benefit (Ashley et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Improving survival in recurrent medulloblastoma: earlier detection, better treatment or still an impasse?

Bouffet

Doz²,

Demaille³

et al. 1998

Br J Cancer

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Summary Early detection of relapse has been advocated to improve survival in children with recurrent medulloblastoma. However, the prognostic factors and the longer term outcome of these patients remains unclear. Pattern of recurrences were analysed in three consecutive protocols of the Societe Frangaise d'Oncologie Pediatrique . A uniform surveillance programme including repeated lumbar puncture combined with computerized tomography (CT) or magnetic resonance imaging (MRI) scan was applied for all registered patients. Forty-six out of 116 patients had progressive or recurrent disease. The median time from diagnosis to recurrence was 10.5 months and 76% relapses occurred during the first 2 years. Seventeen patients had asymptomatic relapses that were detected by the surveillance protocol. Forty-one patients were treated at time of progression. Twenty-three responded to salvage therapy and 11 achieved a second complete remission. The median survival time after progression was 5 months (<1-41 months), and only two patients remained alive at time of followup. Length of survival is primarily related to some specific patterns of relapse (time from diagnosis to recurrence, circumstances of relapse, extent of relapse) and to the response to salvage therapy. No evidence of long-term benefit appeared from any form of treatment.

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Response of recurrent medulloblastoma to low-dose oral etoposide.

Abstract: This report demonstrates the activity of oral VP-16 in the treatment of a small cohort of pretreated patients with recurrent medulloblastoma. This form of administration of oral VP-16 was well tolerated and produced modest toxicity.

Cited by 125 publications

References 9 publications

Possible benefits of high-dose chemotherapy and autologous stem cell transplantation for adults with recurrent medulloblastoma

Possible benefits of high-dose chemotherapy and autologous stem cell transplantation for adults with recurrent medulloblastoma

Changes Mimicking New Leptomeningeal Disease After Intensity-Modulated Radiotherapy for Medulloblastoma

Improving survival in recurrent medulloblastoma: earlier detection, better treatment or still an impasse?

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