Extracorporeal apheresis system - A nanoparticle drugs' elimination method to enhance the benefit of cytostatic therapy in cancer patients
Abstract
Cytostatic treatment is often negatively affected by dose-limited toxicities. Novel agents, including nanoparticle-based drug delivery systems (DDS), are becoming available to overcome this problem.
Despite achieving a lesser toxicity in exchange for more favorable pharmacokinetic profiles, the use of DDS is often associated with a particular toxicity profile. The accumulation of DDS in tumor tissue is much faster than in normal tissues where toxic events occur.
While only a small amount of DDS is delivered to the target tissue, and accumulated there, most of the administered dose remains in circulation. The removal of this fraction, which is no longer effective, is thought to reduce toxicity.
Pegylated liposomal doxorubicin (PLD) has been proven to be effective in platinum-resistant ovarian carcinoma with the reduced risk for cardiotoxicity. Once saturation in tumor tissue is achieved, prolonged circulation seems ineffective, whereas other toxicity risks (palmar-plantar erythrody sesthesia and mucositis) have been reported.
Therefore, extracorporeal elimination of circulating nanoparticles using plasma filtration would probably reduce this risk of toxicity. The elimination rate could be kinetically regulated, i.e. based on individual doxorubicin pharmacokinetic variables.
Plasma filtration can significantly influence the exposure to PLD (plasma concentration-time profile-AUC of PLD) and would be a suitable, well tolerated method enabling individualized, more effective and safer chemotherapy.