Convection-enhanced Delivery for the Treatment of Brain Tumors
As for the near future, we propose the following developmental steps for making CED an effective way of delivering antineoplastic drugs, and recombinant cytotoxins in particular, to brain tumors. Patients' tumors should be prescreened for the target the drug is engineered against, unless the infusate is a combination of drugs that makes all patients likely responders. Moreover, there is a need for more optimal catheters and more precise stereotactic placement directly into the tumor parenchyma and into the surrounding tumor-infiltrated brain. There are likely to be roles for multiport/multicannula or hollow-fiber catheters, which would provide more uniform distribution to larger effective volumes and antireflux protection at the same time. Balloon-tipped catheters await more experimental verification when tumors are resected. Perhaps most importantly, imaging must accompany CED in order to prove an effective distribution of drugs within tumors and tumor-infiltrated brain in each individual patient. The use of computerized algorithms may be helpful for catheter placement, but cannot and will not predict leakage and a subsequent futility of CED in every case. More attention should be paid to the development of pharmacologic formulations of drugs and carriers in preclinical models. Repetition with more than one cycle of CED is also suggested as it is difficult to expect optimal therapeutic results from a single application. These aggressive strategies may initially limit the number of centers capable of performing optimized CED; however, the benefit to patients is likely to be sufficiently high to justify this limitation.
Expert Commentary
As for the near future, we propose the following developmental steps for making CED an effective way of delivering antineoplastic drugs, and recombinant cytotoxins in particular, to brain tumors. Patients' tumors should be prescreened for the target the drug is engineered against, unless the infusate is a combination of drugs that makes all patients likely responders. Moreover, there is a need for more optimal catheters and more precise stereotactic placement directly into the tumor parenchyma and into the surrounding tumor-infiltrated brain. There are likely to be roles for multiport/multicannula or hollow-fiber catheters, which would provide more uniform distribution to larger effective volumes and antireflux protection at the same time. Balloon-tipped catheters await more experimental verification when tumors are resected. Perhaps most importantly, imaging must accompany CED in order to prove an effective distribution of drugs within tumors and tumor-infiltrated brain in each individual patient. The use of computerized algorithms may be helpful for catheter placement, but cannot and will not predict leakage and a subsequent futility of CED in every case. More attention should be paid to the development of pharmacologic formulations of drugs and carriers in preclinical models. Repetition with more than one cycle of CED is also suggested as it is difficult to expect optimal therapeutic results from a single application. These aggressive strategies may initially limit the number of centers capable of performing optimized CED; however, the benefit to patients is likely to be sufficiently high to justify this limitation.
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