Vincristine pharmacokinetics and response to vincristine monotherapy in an up-front window study of the Dutch Childhood Leukaemia Study Group (DCLSG)

TRAIL/Apo-2L has shown promise as an anti-glioma drug, based on investigations of TRAIL sensitivity in established glioma cell lines, but it is not known how accurately TRAIL signalling pathways of glioma cells in vivo are reproduced in these cell lines in vitro. To replicate as closely as possible the in vivo behaviour of malignant glioma cells, 17 early passage glioma cell lines and 5 freshly resected gliomas were exposed to TRAIL-based agents and/or chemotherapeutic drugs. Normal human hepatocytes and astrocytes and established glioma cell lines were also tested. Cross-linked TRAIL, but not soluble TRAIL, killed both normal cell types and cells from three tumours. Cells from only one glioma were killed by soluble TRAIL, although only inefficiently. High concentrations of cisplatin were lethal to glioma cells, hepatocytes and astrocytes. Isolated combinations of TRAIL and chemotherapy drugs were more toxic to particular gliomas than normal cells, but no combination was generally selective for glioma cells. This study highlights the widespread resistance of glioma cells to TRAIL-based agents, but suggests that a minority of high-grade glioma patients may benefit from particular combinations of TRAIL and chemotherapy drugs. In vitro sensitivity assays may help identify effective drug combinations for individual glioma patients.

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“…Peak plasma concentration was 40.5 ng ml À1 but rapidly decreased to 5 ng ml À1 (Groninger et al, 2005) Procarbazine 540 ng ml À1 54 ng ml À1…”

Section: P53 Genotypingmentioning

confidence: 99%

In vitro sensitivity testing of minimally passaged and uncultured gliomas with TRAIL and/or chemotherapy drugs

et al. 2008

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“…2. The vincristine plasma concentrations versus time curve shows the characteristic biphasic elimination of this drug [11,12] with a fast initial distribution rate followed by a very slow elimination process (Fig. 3).…”

Section: Methods Applicationmentioning

confidence: 98%

Validation of an electrospray ionization LC/MS/MS method for quantitative analysis of vincristine in human plasma samples

Guilhaumou

Solas

Rome

et al. 2010

Journal of Chromatography B

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“…23 Results of the pharmacokinetic and dynamic studies of vincristine and PEG-asparaginase given upfront before start of the combination chemotherapy are published elsewhere. 14,15,16 Treatment results according to presenting features Tables 3-6 show the outcomes per study according to the NCI criteria. 20 In the BFM-based protocols ALL-7 and ALL-8, a poor outcome is related to NCI HR criteria, male gender (only ALL-8 study), T-lineage ALL and a high WBC.…”

Section: Tablementioning

confidence: 99%

“…NHR patients had an initial WBC count o50 Â 10 9 /l, no mediastinal mass, no initial CNS involvement, no testicular disease, no T-cell immunophenotype (from March 1998), absence of t(9;22) or BCR-ABL rearrangement and absence of 11q23 abnormalities with mixed lineage leukemia rearrangement. Part of the patients were included in research projects that studied pharmacokinetics andFdynamics of one additional dose of vincristine 14 or PEG-asparaginase before start of therapy. 15,16 The treatment protocol for NHR patients was identical to the ALL-6.…”

Section: Patients and Treatmentmentioning

confidence: 99%

Long-term results of Dutch Childhood Oncology Group studies for children with acute lymphoblastic leukemia from 1984 to 2004

et al. 2009

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The Dutch Childhood Oncology Group (DCOG) has used two treatment strategies for children with acute lymphoblastic leukemia (ALL) based on Pinkel's St Jude Total Therapy or the Berlin-Frankfurt-Mü nster (BFM) backbone. In four successive protocols, 1734 children were treated. Studies ALL-6 and ALL-9 followed the Total Therapy approach; cranial irradiation was replaced by medium-dose methotrexate infusions and prolonged triple intrathecal therapy; dexamethasone was used instead of prednisone. Studies ALL-7 and ALL-8 had a BFM backbone, including more intensive remission induction, early reinduction and maintenance therapy without vincristine and prednisone pulses. The 5-year event-free survival and overall survival increased from 65.4 to 80.6% (Po0.001) and from 78.7 to 86.4% (P ¼ 0.07) in ALL-7 and ALL-9, respectively. In ALL-7 and ALL-8 National Cancer Institute (NCI) high-risk criteria, male gender, T-lineage ALL and high white blood cells (WBCs) predict poor outcome. In ALL-9 NCI criteria, gender, WBC 4100 Â 109/l, and T-lineage ALL have prognostic impact. We conclude that the chemotherapy-only approach in children with ALL in Total Therapy-based strategies and BFM-backbone treatment does not jeopardize survival and preserves cognitive functioning. This experience is implemented in the current DCOG-ALL-10 study using a BFM backbone and minimal residual disease-based stratification.

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Vincristine pharmacokinetics and response to vincristine monotherapy in an up-front window study of the Dutch Childhood Leukaemia Study Group (DCLSG)

Cited by 29 publications

References 19 publications

In vitro sensitivity testing of minimally passaged and uncultured gliomas with TRAIL and/or chemotherapy drugs

In vitro sensitivity testing of minimally passaged and uncultured gliomas with TRAIL and/or chemotherapy drugs

Validation of an electrospray ionization LC/MS/MS method for quantitative analysis of vincristine in human plasma samples

Long-term results of Dutch Childhood Oncology Group studies for children with acute lymphoblastic leukemia from 1984 to 2004

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