Chemotherapeutic dose intensification for treatment of malignant brain tumors: Recent developments and future directions

Abstract

Despite a large amount of research on malignant brain tumors over the past 70 years, the prognosis for most tumor types is poor. One current focus of research is increasing dose intensity of chemotherapeutic agents. Various ways to increase dose intensity include high-dose chemotherapy followed by stem cell rescue (eg, bone marrow transplant), blood-brain barrier disruption or use of RMP7 to increase transvascular drug delivery, local delivery of chemotherapeutic agents (convection enhancement or clysis, antibody conjugates, and biodegradable polymers), chemoprotective agents, and tumor sensitizers. Improved identification of patients likely to respond to a given regimen may also increase the effectiveness of chemotherapy. We also discuss approaches to improve the design of nonrandomized trials by identifying and controlling potential confounding variables. This will improve the quality of individual studies and perhaps the comparability across studies.

Enhanced chemotherapy delivery by intraarterial infusion and blood‐brain barrier disruption in the treatment of cerebral metastasis

“…It involves the IA infusion of chemotherapy with or without prior administration of a hypertonic solution to produce a transient increase in permeabilization of the barrier in a given cerebrovascular distribution. 15,16 The so-called IA chemotherapy infusion refers to the regional delivery of chemotherapy to the CNS, which produces a significant increase in plasma peak concentration and in the area under the curve related to the first pass effect. 13 This translates in a significant increase in intra-tumoral chemotherapy concentration by a 3-5.5-fold factor, as most of these lesions are highly vascularized.…”

“…13,14 This strategy can also be augmented by manipulating the BBB permeability through different means. 15,16 To date, there is no consensus on the role of these approaches in the treatment of brain metastases. We hereby relate our experience with the IA administration of chemotherapy in cerebral metastatic disease, with and without osmotic blood-brain barrier disruption (BBBD).…”

Blood—brain barrier permeability in healthy rats and rats with experimental C6 glioma after fractionated radiotherapy of the brain

“…Было показа-но увеличение проницаемости при ежедневном фракционировании в 3 Гр и по достижению суммар-ной дозы в 30 Гр, в области головного мозга, погра-ничных с полем облучения, причем степень увели-чения была прямо пропорциональна дозе ионизиру-ющего излучения [10]. Для уменьшения долгосроч-ной токсичности предпочтительнее фракциониро-вание с разовой ежедневной дозой 2 Гр [27]. В дру-гом исследовании [12] показано, что фракционная доза 2 Гр для изменения проницаемости ГЭБ может оптимизировать эффект химиотерапии.…”

“…ОРИГИНАЛЬНЫЕ СТАТЬИ лекарственных средств на фоне радиотерапии мы опирались на полученные результаты радиотерапии в дозозависимом эксперименте: чем выше доза ра-зовой фракции, тем очевиден противоопухолевый эффект [27]. При 6-дневном облучении разовой до-зой в 6 Гр объем глиомы не увеличивался с начала радиотерапии, но по завершению эксперимента крысы в течение 2-3 дней погибали от побочных эффектов.…”

“…рис. 7) [27]. При этом однократное введение ан-тител в дозе 1 мг увеличивало продолжительность жизни животных до 56 дней.…”