Pilot study of high-dose thiotepa and etoposide with autologous bone marrow rescue in children and young adults with recurrent CNS tumors. The Children's Cancer Group.

Finlay, Jonathan L.; Goldman, Stewart; Wong, M. C.; Cairo, Mitchell S.; Garvin, James H.; August, Charles S.; Cohen, Bruce H.; Stanley, Philip; Zimmerman, Robert A.; Bostrom, Bruce; Geyer, J. Russell; Harris, Richard E.; Sanders, Jean E.; Yates, Allan J.; Boyett, James M.; Packer, Roger J.

doi:10.1200/jco.1996.14.9.2495

Cited by 191 publications

(118 citation statements)

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“…However, despite a high response rate, responses at time of relapse are often transient. This has led to the assessment of high-dose therapy for responding patients using various regimens (Kalifa et al, 1992;Finlay et al, 1996;Mahoney et al, 1996). The most promising results concern high-dose chemotherapy in relapsing infants previously non-irradiated (Dupuis-Girod et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

“…The most promising results concern high-dose chemotherapy in relapsing infants previously non-irradiated (Dupuis-Girod et al, 1996). Encouraging preliminary survival data have been reported by Finlay (1996) with the use of high-dose chemotherapy in patients with recurrent medulloblastoma. In this experience, children with minimal tumour burden are the ones who benefit from myeloablative strategies.…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

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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“…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. [10][11][12][13][14][15] Here, we report the outcomes of six adults who underwent HDCT (cyclophosphamide, carboplatin, thiotepa, etoposide) with ASCT for medulloblastoma relapse. Table 1 lists the clinical profile of patients 1-6.…”

mentioning

confidence: 99%

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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“…11 Etoposide has exhibited a good level of penetration into brain parenchyma as well, 12 and both of these agents have demonstrated good activity against recurrent brain tumors at conventional doses. [13][14][15] Finlay et al 20 treated 45 patients with high doses of etoposide (1500 mg/m 2 ) and thiotepa (900 mg/m 2 ) followed by autologous stem cell rescue; those investigators obtained a 23% CR ϩ PR rate in heavily pretreated patients and a 16% toxicity-related death rate. Bouffet et al 21 treated 22 patients with recurrent or newly diagnosed high-grade glioma and reported a 29% response rate (1 CR and 3 PRs) along with an OS rate no better than what had been achieved using conventional treatment.…”

Section: Discussionmentioning

confidence: 99%

High‐dose thiotepa and etoposide in children with poor‐prognosis brain tumors

Biasin¹,

Mastrodicasa²,

Sandri³

et al. 2004

Cancer

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BACKGROUNDOutcome data were analyzed for 27 patients who were affected with recurrent or newly diagnosed high‐risk brain tumors and who underwent high‐dose chemotherapy with triethylenethiophosphoramide (thiotepa) and etoposide in addition to autologous stem cell transplantation between May 1992 and September 2002.METHODSFifteen males and 12 females (median age, 11 years) were included in the study. Twelve patients had newly diagnosed high‐risk brain tumors, and 15 patients had recurrent brain tumors. The conditioning regimen consisted of thiotepa 900 mg/m2 and etoposide 1500 mg/m2 over 3 days starting on Day −5. Stem cell rescue was performed using bone marrow (BM) in 8 patients, peripheral blood stem cells (PBSCs) in 18 patients, and BM and PBSCs in 1 patient.RESULTSFor the BM group, neutrophil (PMN) engraftment was achieved on Day +14 (median value), whereas platelet (PLT) engraftment was achieved on Day +68 (median value). One patient did not achieve PLT engraftment. For the PBSC group, the PMN engraftment was achieved on Day +10.0 (median value), and the PLT engraftment was achieved on Day +15.5 (median value). Transplantation‐related toxicity (evaluated using the Bearman score) included Grade 2–3 mucositis in 16 patients, Grade 1 kidney toxicity in 6 patients, Grade 1 liver toxicity in 6 patients, and Grade 2 liver toxicity in 1 patient. Transplantation‐related mortality was observed in 1 patient (3.6%), who died of Candida pneumonia. The 3‐year overall survival (OS) rate was 44.6%, and the 3‐year event‐free survival (EFS) rate was 31%. There was a statistically significant difference in OS and EFS rates for patients who underwent ASCT and achieved complete remission compared with patients who had measurable disease.CONCLUSIONSThe results of the current study suggest that high‐dose chemotherapy followed by ASCT may be beneficial for patients who achieve complete remission before ASCT, whereas for other patients, new strategies are required. Cancer 2004. © 2004 American Cancer Society.

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Pilot study of high-dose thiotepa and etoposide with autologous bone marrow rescue in children and young adults with recurrent CNS tumors. The Children's Cancer Group.

Abstract: The combination of high-dose thiotepa and etoposide has activity against a variety of recurrent childhood brain tumors. These results merit further evaluation in children and young adults with both recurrent and newly diagnosed high-grade brain tumors.

Cited by 191 publications

References 15 publications

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

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

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

High‐dose thiotepa and etoposide in children with poor‐prognosis brain tumors

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