Kinetic Targeting of pegylated liposomal Doxorubicin: a new Approach to Reduce Toxicity during Chemotherapy (CARL-trial)
1 Medical Practice, Altdorfstr. 10, Emmendingen, Germany
2 Dept. Hematology & Oncology; University Medical Center Freiburg, Hugstetter Str. 55, Freiburg, Germany
3 Dept. Gynecology, St. Josephs Hospital Offenburg, Offenburg, Germany
4 Dept. Nephrology; University Medical Center Freiburg, Hugstetter Str. 55, Freiburg, Germany
5 Dept. of Gynecology and Obstetrics, University Medical Center Freiburg, Hugstetter Str. 55, Freiburg, Germany
6 Pharmacy; University Medical Center Freiburg, Hugstetter Str. 55, Freiburg, Germany
7 Dept. Clinical Chemistry; University Medical Center Freiburg, Hugstetter Str. 55, Freiburg, Germany
BMC Cancer 2011, 11:337 doi:10.1186/1471-2407-11-337Published: 4 August 2011
The therapeutic success of chemotherapeutic agents is often limited by severe adverse effects. To reduce toxicity of these drugs, nanoscale particle-based drug delivery systems (DDS) are used. DDS accumulate to some extent in tumor tissues, but only a very small portion of a given dose reaches this target. Accumulation of DDS in tumor tissues is supposed to be much faster than in certain other tissues in which side effects occur ("Kinetic Targeting"). Once saturation in tumor tissue is achieved, most of the administered DDS still circulate in the plasma. The extracorporeal elimination of these circulating nanoparticles would probably reduce toxicity.
For the CARL-trial (
DFPP eliminated ~62% of circulating PLD, corresponding to ~45% of the total dose (n = 57 cycles). AUC of doxorubicin was reduced by 50%. No leakage of doxorubicin was detected during elimination, and no relevant DFPP-related side effects occurred. Reduction in tumor size > 30% occurred in 10/12 (neoadjuvant) and in 1/3 patients (recurrent). Only five grade 2 events and one grade 3 event (mucositis, neutropenia or leucopenia) and a single palmar-plantar erythrodysesthesia grade 2 were reported.
Extracorporeal elimination of PLD by DFPP is safe and efficient. CARL can diminish the main dose-limiting side effects of PLD, and probably many different DDS alike.