Will Hemoperfusion Be Useful for Cancer Chemotherapeutic Drug Removal?

Abstract

One of the major problems in clinical cancer chemotherapy is the inability to safely administer full therapeutic doses of specific drugs in the face of dysfunction of an organ system controlling that drug's metabolism and excretion. Should efficient drug removal from blood be possible following full therapeutic doses and after tumor exposure, then theoretically, even in the presence of organ dysfunction, anticancer drug toxicity may be reduced or avoided. Preliminary experiments in our laboratory have shown that adriamycin may be efficiently removed by activated charcoal from aqueous and protein solutions and blood in vivo, and that daunorubicin is removed in vitro to the same extent. However, although methotrexate is removed efficiently in vitro and extracted 50% in vivo by charcoal hemoperfusion, its overall pharmacokinetics do not appear to be altered in comparison with the alteration in pharmacokinetics of adriamycin achieved with charcoal hemoperfusion. Computer modeling has suggested that efficient adriamycin removal is achievable, and that clinical studies are warranted. For methotrexate removal, however, previous clinical studies and our own data suggest that charcoal hemoperfusion has little utility unless a highly specific sorbent for methotrexate removal can be developed.

Hemoperfusion for the Treatment of Poisoning: Technology, Determinants of Poison Clearance, and Application in Clinical Practice

“…Coating reduces embolization of the particles and improves the biocompatibility of charcoal columns . However, coating can also reduce the in vitro clearance of several poisons, especially larger molecular weight compounds (>5000 Da) , although this has not been consistently observed in animal and human reports . In some publications, poison clearance using coated columns has even surpassed uncoated cartridges , although this could reflect other factors such as the structure of column.…”

Extracorporeal Treatment for Methotrexate Poisoning

“…Methotrexate has a low molecular weight and moderate protein binding, so it passes easily through modern dialyzers and hemofilters, which is confirmed by in vitro and animal experiments (174). Activated charcoal adsorbs methotrexate better than resins (177,183), although both are limited by cartridge saturation (176). In one porcine study, resin hemoperfusion provided a two- to three-fold greater initial clearance than hemodialysis, which was negated at 3 hours because of saturated adsorption (178).…”

“…A total of 1376 articles were identified after removal of duplicates. In the final analysis, 92 articles were included, including two in vitro experiments (174,175), four animal experiments (176)(177)(178)(179), 84 case reports and case series (24, 35,88,90,126,163,170,171,, one pharmacokinetic modeling study (256), and one observational study (160). Although several articles were designed as pharmacokinetic studies in kidney failure patients (170,190,204,225,242), many participants in these studies developed methotrexateassociated toxicity and were included in case reports.…”