Efficacy and toxicity profile of pegylated liposomal doxorubicin (Caelyx) in patients with advanced breast cancer

Abstract

Many patients with metastatic breast cancer (MBC) have been treated previously with taxanes and/or anthracyclines, which renders reinduction of anthracyclines in the palliative setting impossible because of the high cardiotoxicity of these drugs. Pegylated liposomal doxorubicin represents a means of reinducing anthracyclines without increasing cardiotoxicity. The aim of this retrospective study was to evaluate the efficacy and toxicity of Caelyx in patients with MBC. Patients with histologically confirmed MBC were eligible for this retrospective study if they had received palliative chemotherapy with pegylated liposomal doxorubicin between 1 January 2002 and 31 December 2006 at the Department for Gynecology and Obstetrics at the University of Heidelberg (Germany). The main endpoints were time to progression, overall survival, and safety of the treatment with pegylated liposomal doxorubicin. In all, 141 patients were included in this retrospective trial. The median age of the patients was 54 years (range 24-84 years). Of the patients, 43% had received five to six previous chemotherapy regimens before pegylated liposomal doxorubicin was recommended. In 33% of patients, more than three organs were involved. The most commonly involved organs were bones, liver, and lungs; 37 patients had received three or at least six cycles of Caelyx. During the treatment with pegylated liposomal doxorubicin, left ventricular ejection function was not reduced by more than 15%. The major effects (grade 4) were hematological toxicity (anemia, leukopenia, and thrombocytopenia), hand-foot syndrome, and stomatitis. In nine patients, the dose was reduced and in three patients chemotherapy with Caelyx was stopped owing to hematological toxicity. In 20 patients, the dose was reduced and in nine patients chemotherapy was stopped owing to nonhematological toxicity. The median time to disease progression was 6.5 months; the overall median survival was 13 months after the first course of pegylated liposomal doxorubicin was initiated. This retrospective study confirmed the efficacy and good tolerability of pegylated liposomal doxorubicin in patients with MBC who had been treated previously with anthracycline. A dosage of 40 mg/m² body surface every 4 weeks is equally effective with less toxicity.

Poly(ethylene glycol)-block-poly(ε-caprolactone)– and phospholipid-based stealth nanoparticles with enhanced therapeutic efficacy on murine breast cancer by improved intracellular drug delivery

“…This surface modification reduces clearance of nanoparticles by the cells of the RES and apparently prolongs the duration of nanoparticles remaining in circulation. 5,[7][8][9] Lipid-PEGs, especially DSPE-PEG2000, have been extensively used to prepare stealth liposomes. 7,8,10,11 Although the PEG-coating brings prolonged circulation time and enhanced accumulation at the tumor site via the EPR effect, the highly hydrophilic surface is unfavorable for the internalization of liposomes by tumor cells.…”

“…5,[7][8][9] Lipid-PEGs, especially DSPE-PEG2000, have been extensively used to prepare stealth liposomes. 7,8,10,11 Although the PEG-coating brings prolonged circulation time and enhanced accumulation at the tumor site via the EPR effect, the highly hydrophilic surface is unfavorable for the internalization of liposomes by tumor cells. 3,6,10 Thus, the anticancer efficiency of stealth liposomes containing DSPE-PEG2000 both in vitro and in vivo is far from what has been expected.…”

Functionalization of Alkyne-Terminated Thermally Hydrocarbonized Porous Silicon Nanoparticles With Targeting Peptides and Antifouling Polymers: Effect on the Human Plasma Protein Adsorption

“…The obtained yield was 5.9 g (91%). 1 H NMR analysis was performed in DMSO-d 6 Figure S1). The Fourier transform infrared spectroscopy (FTIR) spectrum ( Figure S2) was performed to verify the presence of the N 3 group at the reducing end.…”

Doxorubicin‐loaded poly(ε‐caprolactone)‐Pluronic micelle for targeted therapy of esophageal cancer

“…5,6 Previous studies have indicated that doxorubicin (DOX) is very effective in breast cancer, ovarian cancer, prostate cancer, brain cancer, cervix cancer, and lung cancers. 7 However, there are still some shortcomings, including cardiac toxicity, short half-life, low solubility of aqueous solution, hindering its application. In addition, multidrug resistance (MDR) for various cancers is also an obstacle to the development of anticancer drugs.…”