Association of total dose intensity of chemotherapy in primary central nervous system lymphoma (Human non-acquired immunodeficiency syndrome) and survival

OBJECTIVE: The importance of enhanced drug delivery in patients with centra l nervous system (CNS) malignancies has not yet been demonstrated conclusiv ely. Intra-arterial chemotherapy in combination with osmotic blood-brain ba rrier disruption (BBBD) increases drug delivery to tumor by 2- to 5-fold an d to surrounding brain tissue by 10- to 100-fold as compared with intraveno us administration of chemotherapy. Primary CNS lymphoma (PCNSL) is an excel lent model for studying dose intensity because PCNSL is a highly infiltrati ve, chemosensitive, primary CNS malignancy in which the integrity of the bl ood-brain barrier is highly variable. METHODS: Survival time was assessed in 74 non-acquired immunodeficiency syn drome patients with PCNSL who underwent a total of 1047 BBBD procedures. To tal dose intensity is estimated by using the number of intraarterial infusi ons or a cumulative degree of BBBD score. RESULTS: Using proportional hazards multivariabie analyses to adjust for ba seline characteristics, survival was significantly associated with the tota l intensity of BBBD (P < 0.05). Additional statistical analyses demonstrate that survival bias does not fully explain these associations. Even when on ly 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, s urvival time is highly associated with total drug dose delivered, even in a nalyses designed to control for potential survival biases. These results pr obably constitute the strongest evidence to date of the importance of total dose intensity in treating CNS malignancies.