Based on the previously described roles of doxorubicin in immunogenic cell death, both doxorubicin and liposomal doxorubicin (Doxil) were evaluated for their ability to boost the antitumor response of different cancer immunotherapies including checkpoint blockers (anti-PD-L1, PD-1, and CTLA-4 mAbs) and TNF receptor agonists (OX40 and GITR ligand fusion proteins) in syngeneic mouse models. In a ...

In preclinical studies, a doxorubicin liposome formulation containing polyethylene-glycol (Doxil) shows a long circulation time in plasma, enhanced accumulation in murine tumors, and a superior therapeutic activity over free (unencapsulated) doxorubicin (DOX). The purpose of this study was to characterize the pharmacokinetics of Doxil in cancer patients in comparison with free DOX and examine i...

PURPOSE Doxorubicin chemomyectomy presently represents the only permanent, nonsurgical treatment for blepharospasm and hemifacial spasm. The major deterrent to an otherwise extremely effective treatment protocol is the development in patients of localized inflammation, discomfort, and skin injury over the injection site. As a potential alternative therapy, Doxil (Sequus, Menlo Park, CA), a lipo...

BACKGROUND We have previously demonstrated that vincristine, liposomal doxorubicin and dexamethasone (VAD-doxil) is equally effective with VAD-bolus yielding objective response rates of 61% as first-line treatment in multiple myeloma (MM). In a phase II study, the addition of thalidomide to VAD-doxil (TVAD-doxil) proved feasible and increased response rate to 74%. The aim of the present multice...

PURPOSE Our first objective was to evaluate the feasibility of administering a combination of Doxil, a pegylated liposome formulation of doxorubicin, and cisplatin and to determine the maximum tolerated dose of the combination. A secondary objective was to examine Doxil peak and 7-day postinjection plasma levels at the various dose levels tested. METHODS Patients with advanced solid tumors we...

Combining radiofrequency (RF) ablation with i.v. liposomal doxorubicin (Doxil) increases intratumoral doxorubicin accumulation and tumor destruction. The purpose of this study was to characterize and better define the specific parameters of such treatment in an animal tumor model. Four hundred R3230 mammary adenocarcinoma nodules were implanted in 250 Fischer rats. First, paired tumors received...

Pharmacokinetic and organ distribution studies of liposomal drugs in humans are a challenge. A direct labeling method using (99m)Tc-N,N-bis(2-mercaptoethyl)-N',N'-diethyl-ethylenediamine (BMEDA) complex to label the commercially available pegylated liposomal doxorubicin, Doxil, has been introduced. Biodistributions of (99m)Tc-Doxil in normal rats were performed to evaluate the feasibility of us...

PURPOSE To determine the maximum tolerated dose and pharmacokinetics of Doxil in children with recurrent or refractory solid tumors. Doxil is pegylated doxorubicin. EXPERIMENTAL DESIGN Eligible patients were children with refractory tumors who had received cumulative anthracycline doses <300 mg/m(2). Cohorts of at least three patients each received escalating doses of Doxil starting at 40 mg/...

PURPOSE To test the safety and effectiveness of Doxil chemomyectomy in monkey eyelids using treatment schedules and doses similar to those proposed for the human blepharospasm patients in Phase I and II trials. METHODS Bupivacaine/hyaluronidase and Doxil were injected sequentially into the eyelids of five Cynomolgus monkeys. Eyelids received 1, 2, or 3 sets of injections. The monkeys were eut...

A central treatment resistance mechanism in solid tumors is the maintenance of epithelial junctions between malignant cells that prevent drug penetration into the tumor. We have developed a small recombinant protein (JO-1) that triggers the transient opening of intercellular junctions and thus increases the efficacy of monoclonal antibodies and chemotherapeutic drugs without causing toxicity in...