Decreased delivery and acute toxicity of cranial irradiation and chemotherapy given with osmotic blood-brain barrier disruption in a rodent model: the issue of sequence.

摘要: The sequence of chemotherapy administered prior to cranial irradiation rather than the more traditional order radiation followed by is currently being evaluated. This rodent study was designed assess sequencing therapy and with osmotic blood-brain barrier disruption (BBBD). Drug delivery acute toxicity were Two clinically relevant regimens given BBBD: intraarterial methotrexate (MTX, 1 g/m2), or a combination carboplatin (200 mg/m2) i.v. etoposide mg/m2). In randomized protocol, standard model 2000 cGy as single fraction using parallel opposed portals 30 days to, concurrent (24 h prior), after these two chemotherapeutic regimens. A total 72 animals evaluated in this study. administration external beam either high molecular weight marker 14C-labeled dextran 70 (Mr 70,000), low 3H-labeled MTX 456) resulted statistically significant (P < 0.01) decrease drug when compared not receiving irradiation. Seizures observed 26% that received BBBD. It did matter whether radiotherapy MTX. seen any other group. mortality significantly = 0.03) higher control BBBD, but no radiation. decreased radiotherapy; BBBD an increased incidence seizures, there increase With regard toxicity, may have advantages over sequences utilizing