Association of total dose intensity of chemotherapy in primary central nervous system lymphoma (human Non-Acquired Immunodeficiency Syndrome) and survival

Dale Kraemer, David Fortin, Nancy Doolittle, Edward Neuwelt

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54 Citations (Scopus)

Abstract

OBJECTIVE: The importance of enhanced drug delivery in patients with central nervous system (CNS) malignancies has not yet been demonstrated conclusively. Intra-arterial chemotherapy in combination with osmotic blood-brain barrier disruption (BBBD) increases drug delivery to tumor by 2- to 5-fold and to surrounding brain tissue by 10- to 100-fold as compared with intravenous administration of chemotherapy. Primary CNS lymphoma (PCNSL) is an excellent model for studying dose intensity because PCNSL is a highly infiltrative, chemosensitive, primary CNS malignancy in which the integrity of the blood-brain barrier is highly variable. METHODS: Survival time was assessed in 74 non-acquired immunodeficiency syndrome patients with PCNSL who underwent a total of 1047 BBBD procedures. Total dose intensity is estimated by using the number of intra-arterial infusions or a cumulative degree of BBBD score. RESULTS: Using proportional hazards multivariable analyses to adjust for baseline characteristics, survival was significantly associated with the total intensity of BBBD (P <0.05). Additional statistical analyses demonstrate that survival bias does not fully explain these associations. Even when only patients who attained a complete response are considered, increased dose intensity resulted in increased survival. CONCLUSION: In patients with PCNSL, a chemotherapy-responsive tumor type, survival time is highly associated with total drug dose delivered, even in analyses designed to control for potential survival biases. These results probably constitute the strongest evidence to date of the importance of total dose intensity in treating CNS malignancies.

Original languageEnglish (US)
Pages (from-to)1033-1041
Number of pages9
JournalNeurosurgery
Volume48
Issue number5
StatePublished - 2001

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Blood-Brain Barrier
Lymphoma
Central Nervous System
Drug Therapy
Survival
Neoplasms
Pharmaceutical Preparations
Intra Arterial Infusions
Survival Analysis
Combination Drug Therapy
Intravenous Administration
Brain

Keywords

  • Blood-brain barrier
  • Central nervous system lymphoma
  • Chemotherapy
  • Dose intensity

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery

Cite this

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abstract = "OBJECTIVE: The importance of enhanced drug delivery in patients with central nervous system (CNS) malignancies has not yet been demonstrated conclusively. Intra-arterial chemotherapy in combination with osmotic blood-brain barrier disruption (BBBD) increases drug delivery to tumor by 2- to 5-fold and to surrounding brain tissue by 10- to 100-fold as compared with intravenous administration of chemotherapy. Primary CNS lymphoma (PCNSL) is an excellent model for studying dose intensity because PCNSL is a highly infiltrative, chemosensitive, primary CNS malignancy in which the integrity of the blood-brain barrier is highly variable. METHODS: Survival time was assessed in 74 non-acquired immunodeficiency syndrome patients with PCNSL who underwent a total of 1047 BBBD procedures. Total dose intensity is estimated by using the number of intra-arterial infusions or a cumulative degree of BBBD score. RESULTS: Using proportional hazards multivariable analyses to adjust for baseline characteristics, survival was significantly associated with the total intensity of BBBD (P <0.05). Additional statistical analyses demonstrate that survival bias does not fully explain these associations. Even when only patients who attained a complete response are considered, increased dose intensity resulted in increased survival. CONCLUSION: In patients with PCNSL, a chemotherapy-responsive tumor type, survival time is highly associated with total drug dose delivered, even in analyses designed to control for potential survival biases. These results probably constitute the strongest evidence to date of the importance of total dose intensity in treating CNS malignancies.",
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T1 - Association of total dose intensity of chemotherapy in primary central nervous system lymphoma (human Non-Acquired Immunodeficiency Syndrome) and survival

AU - Kraemer, Dale

AU - Fortin, David

AU - Doolittle, Nancy

AU - Neuwelt, Edward

PY - 2001

Y1 - 2001

N2 - OBJECTIVE: The importance of enhanced drug delivery in patients with central nervous system (CNS) malignancies has not yet been demonstrated conclusively. Intra-arterial chemotherapy in combination with osmotic blood-brain barrier disruption (BBBD) increases drug delivery to tumor by 2- to 5-fold and to surrounding brain tissue by 10- to 100-fold as compared with intravenous administration of chemotherapy. Primary CNS lymphoma (PCNSL) is an excellent model for studying dose intensity because PCNSL is a highly infiltrative, chemosensitive, primary CNS malignancy in which the integrity of the blood-brain barrier is highly variable. METHODS: Survival time was assessed in 74 non-acquired immunodeficiency syndrome patients with PCNSL who underwent a total of 1047 BBBD procedures. Total dose intensity is estimated by using the number of intra-arterial infusions or a cumulative degree of BBBD score. RESULTS: Using proportional hazards multivariable analyses to adjust for baseline characteristics, survival was significantly associated with the total intensity of BBBD (P <0.05). Additional statistical analyses demonstrate that survival bias does not fully explain these associations. Even when only patients who attained a complete response are considered, increased dose intensity resulted in increased survival. CONCLUSION: In patients with PCNSL, a chemotherapy-responsive tumor type, survival time is highly associated with total drug dose delivered, even in analyses designed to control for potential survival biases. These results probably constitute the strongest evidence to date of the importance of total dose intensity in treating CNS malignancies.

AB - OBJECTIVE: The importance of enhanced drug delivery in patients with central nervous system (CNS) malignancies has not yet been demonstrated conclusively. Intra-arterial chemotherapy in combination with osmotic blood-brain barrier disruption (BBBD) increases drug delivery to tumor by 2- to 5-fold and to surrounding brain tissue by 10- to 100-fold as compared with intravenous administration of chemotherapy. Primary CNS lymphoma (PCNSL) is an excellent model for studying dose intensity because PCNSL is a highly infiltrative, chemosensitive, primary CNS malignancy in which the integrity of the blood-brain barrier is highly variable. METHODS: Survival time was assessed in 74 non-acquired immunodeficiency syndrome patients with PCNSL who underwent a total of 1047 BBBD procedures. Total dose intensity is estimated by using the number of intra-arterial infusions or a cumulative degree of BBBD score. RESULTS: Using proportional hazards multivariable analyses to adjust for baseline characteristics, survival was significantly associated with the total intensity of BBBD (P <0.05). Additional statistical analyses demonstrate that survival bias does not fully explain these associations. Even when only patients who attained a complete response are considered, increased dose intensity resulted in increased survival. CONCLUSION: In patients with PCNSL, a chemotherapy-responsive tumor type, survival time is highly associated with total drug dose delivered, even in analyses designed to control for potential survival biases. These results probably constitute the strongest evidence to date of the importance of total dose intensity in treating CNS malignancies.

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