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Effect of dalteparin and radiation on survival and thromboembolic events in glioblastoma multiforme: a phase II ECOG trial

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Abstract

Laboratory and clinical studies support the concept that heparins, particularly the low molecular component, may serve as an inhibitor of angiogenesis, providing anti-neoplastic effects. Further, treatment with low molecular weight heparin (LMWH) may provide prophylaxis for thromboembolic events (TEE), in glioblastoma (GBM) patients. Dalteparin (5,000 U sub-Q daily) was given with and after conventional radiotherapy to newly diagnosed GBM patients. Forty-five patients were accrued between 5/02 and 9/04; 3 were ineligible. At time of progression, patients could continue dalteparin in addition to standard regimens. Pretreatment characteristics included: median age 61 (range 26–78); ECOG Performance status: 0 = 38%, 1 = 57%, 2 = 5%; gross total resection 45%. There were no grade 3/4 bleeding or thrombocytopenic events, and no TEE occurred while on dalteparin. Median time on dalteparin was 6.3 months, median time to progression was 3.9 months; median survival was 11.9 months. There was no significant improvement in survival when compared to the RTOG GBM database (with various radiation/drug doublets including BCNU) using recursive partitioning analysis. Historically the incidence of TEE in GBM patients is ∼30%. As this study suggests dalteparin reduces the incidence of TEE, and does not have significant overlapping toxicities with most other drugs; its testing in a combined modality approach with other medications may be warranted in future trials.

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Abbreviations

ECOG:

Eastern Cooperative Oncology Group

GBM :

Glioblastoma multiforme

TEE:

Thromboembolic events

LMWH:

Low molecular weight heparin

RTOG:

Radiation Therapy Oncology Group

KPS:

Karnofsky Performance Status

RPA:

Recursive partitioning analysis

DVT:

Deep vein thrombophlebitis

MST:

Median survival time

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Acknowledgments

This study was conducted by the Eastern Cooperative Oncology Group (Robert L. Comis, M.D., Chair) and supported in part by Public Health Service Grants CA23318, CA66636, CA21115, CA21076, CA13650; RTOG U10 CA21661, CCOP U10 CA37422, and Stat U10 CA32115 grants from the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute, Kathleen Reader Memorial Research Fund. Dalteparin was supplied by Pfizer (formerly Pharmacia).

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Authors and Affiliations

  1. Department of Medicine, University of Wisconsin Cancer Center, CSC K4/5, 600 Highland Avenue, Madison, WI, 53792-616, USA

    H. Ian Robins & Minesh Mehta

  2. Dana Farber Cancer Institute, Boston, MA, USA

    Anne O’Neill

  3. M.D. Anderson Cancer Center, Houston, TX, USA

    Mark Gilbert

  4. St Francis Hospital:Oklahoma CCOP, Tulsa, OK, USA

    Mark Olsen

  5. Carle Clinic Cancer Center, Urbana, IL, USA

    Ronald Sapiente

  6. Radiation Therapy Oncology Group, Philadelphia, PA, USA

    Brian Berkey

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  1. H. Ian Robins
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  2. Anne O’Neill
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  4. Mark Olsen
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  5. Ronald Sapiente
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  7. Minesh Mehta
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Correspondence to H. Ian Robins.

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Robins, H.I., O’Neill, A., Gilbert, M. et al. Effect of dalteparin and radiation on survival and thromboembolic events in glioblastoma multiforme: a phase II ECOG trial. Cancer Chemother Pharmacol 62, 227–233 (2008). https://doi.org/10.1007/s00280-007-0596-3

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  • DOI: https://doi.org/10.1007/s00280-007-0596-3

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