title: Controlled application and scheduled removal of nanoparticle based chemotherapeutics (CARL) will reduce dose limiting adverse events in anticancer chemotherapy.
abstract: Clinical success of cancer chemotherapy is impaired by dose limiting toxicities. Nanoscale particle based drug delivery systems (DDS) like long circulating liposomes show improved toxicity profiles. Nevertheless, their unique pharmacokinetic properties lead to new dose limiting adverse events such as elevated skin toxicity. Though DDS accumulate in tumor tissue, only a very small fraction of the total dose reaches the target site. The overwhelming amount of a given dose is needed only to build up a diffusion gradient for effective accumulation at the target site. Due to the altered endothelial barrier, accumulation of DDS in tumor tissue is much faster than accumulation in other tissues, where dose limiting side effects occur. On the basis of these pharmakinetic data we hypothesize, that once accumulation in the tumor tissue is completed, rapid elimination of the DDS fraction still circulating in the plasma may diminish otherwise dose limiting toxicities. Rapid elimination of circulating DDS might be performed by extracorporeal apheresis treatment. Within this paper the principle of kinetic targeting by scheduled extracorporeal elimination of long circulating DDS is presented in detail. Benefits for patients are as well discussed as possible criticisms and future developments. In conclusion, the combination of DDS and scheduled apheresis may allow the development of new chemotherapy regiments with higher impact and/or less toxicity.
authors.affiliation: University Freiburg Medical Center, Department Clinical Chemistry, Hugstetter Street 55, D-79106 Freiburg, Germany. Gerhard.puetz@uniklinik-freiburg.de
authors.forename: Gerhard
authors.initials: G
authors.lastname: Pütz
authors.forename: Oliver
authors.initials: O
authors.lastname: Schmah
authors.forename: Jürgen
authors.initials: J
authors.lastname: Eckes
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Hug
authors.forename: Karl
authors.initials: K
authors.lastname: Winkler
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D053758:Nanoparticles; D009369:Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents