Kinetic Targeting of pegylated liposomal Doxorubicin: a new Approach to Reduce Toxicity during Chemotherapy (CARL-trial)

• Published in: BMC cancer Vol. 11; no. 1; p. 337
• Main Authors: Eckes, Jürgen, Schmah, Oliver, Siebers, Jan W, Groh, Ursula, Zschiedrich, Stefan, Rautenberg, Beate, Hasenburg, Annette, Jansen, Martin, Hug, Martin J, Winkler, Karl, Pütz, Gerhard
• Format: Journal Article
• Language: English
• Published: London BioMed Central 04.08.2011; BioMed Central Ltd; BMC
• Subjects: Adult; Aged; Antibiotics, Antineoplastic - administration & dosage; Antibiotics, Antineoplastic - adverse effects; Antibiotics, Antineoplastic - isolation & purification; Area Under Curve; Biomedical and Life Sciences; Biomedicine; Breast cancer; Breast Neoplasms - blood; Breast Neoplasms - drug therapy; Breast Neoplasms - therapy; Cancer Research; Cancer therapies; Chemotherapy; Clinical oncology; Complications and side effects; Dosage and administration; Doxorubicin; Doxorubicin - administration & dosage; Doxorubicin - adverse effects; Doxorubicin - analogs & derivatives; Doxorubicin - isolation & purification; Doxorubicin - pharmacokinetics; Drug delivery systems; Drug-Related Side Effects and Adverse Reactions - prevention & control; Drugs; Female; Health aspects; Health Promotion and Disease Prevention; Humans; Medicine/Public Health; Middle Aged; Molecular weight; Nanoparticles; Nanoparticles - administration & dosage; Oncology; Ovarian Neoplasms - blood; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - therapy; Plasma; Plasmapheresis; Plasmapheresis - methods; Polyethylene Glycols - administration & dosage; Polyethylene Glycols - adverse effects; Polyethylene Glycols - isolation & purification; Polyethylene Glycols - pharmacokinetics; Quality of Life; Research Article; Skin; Surgical Oncology; Surveys and Questionnaires; Tomography; Toxicity; Tumors; Germany; Pegylated Liposomal Doxorubicin; Doxorubicin; Drug Delivery System; Trastuzumab; Vinorelbine
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/1471-2407-11-337

Background 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. Methods For the CARL-trial ( C ontrolled A pplication and R emoval of L iposomal chemotherapeutics), pegylated liposomal doxorubicin (PLD) was used as chemotherapeutic agent and double filtration plasmapheresis (DFPP) was performed for extracorporeal elimination of liposomes. PLD was given as 40 mg/m 2 every 3 weeks in combination with vinorelbine 2 × 25 mg/m 2 (neoadjuvant treatment of breast cancer, 12 patients), or as 40 mg/m 2 every 4 weeks (recurrent ovarian cancer, 3 patients). Primary endpoints were the efficiency and safety profile of DFPP, and secondary endpoints were side effects and tumor response. Results 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. Conclusion 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. Trial registration DRKS00000163