The toxicity of chemotherapeutic agents, resulting from their low pharmacological index, introduces considerable discomfort and risk to cancer patients. Among several strategies to reduce the toxicity of chemotherapeutic agents, targeted drug delivery is the most promising one. Areas covered: Liposomes, micelles, albumin-based, polymeric, dendritic and lipid core nanoparticles have been used as carriers to concentrate anticancer drugs in neoplastic tissues, and clinical studies of those preparations are reviewed. In most clinical studies, drug delivery systems reduced drug toxicity. Lipid core nanoparticles (LDE) that bind to cell lipoprotein receptors have the ability to concentrate in neoplastic tissues and were the first artificial non-liposomal system shown in in vivo studies to possess targeting properties. The toxicity reduction achieved by LDE as vehicle of carmustine, etoposide and paclitaxel was singularly strong. Expert opinion: The reduced toxicity offered by drug delivery systems has expanded treatment population that may benefit from chemotherapy including feeble, overtreated and elderly patients that would otherwise be offered palliative therapy. Drug delivery systems may either prolong the duration of treatments or allow increases in drug dose.

Ovarian cancer is often diagnosed at advanced stages, when poorly responsive to standard treatment. First-line treatment consists in schemes including cytoreductive surgery followed by adjuvant chemotherapy schemes with platinum and taxane derivatives. Second-line regimens are based on gemcitabine and liposomal doxorubicin. Third line is often not worthwhile because of the high toxicity with poor response to treatment. Previously, we showed that paclitaxel (PTX) carried in non-protein lipid core nanoparticles (LDE) resembling the chemical structure of LDL has remarkably reduced toxicity. Here, the hypothesis was tested whether PTX-LDE could safely benefit patients in third-line treatment setting. Fourteen women unresponsive to second-line chemotherapy for ovarian cancer, aged 61 ± 10 years, clinical stage IV and TqNqM1, were included. PTX-LDE was administered at 175 mg/m, 3/3 week dose. Patients were submitted to clinical examinations before each chemotherapy cycle. Serum biochemistry and imaging examinations to monitor disease progression were performed. In total, 74 cycles of chemotherapy were done and, in all cycles, clinical or laboratorial toxicities were not observed. Median progression-free survival (PFS) was 3.0 months (95% CI 2.0-3.9). In four patients, PFS was >6 months and in 2 > 1 year. The unpreceded, striking absence of toxicity and consistently long PFS, compared to previous results, indicate that at least 4 among 14 patients had tumor arrest by the treatment and clear benefit of PTX-LDE at third-line setting. The absence of observable toxicity allows dose escalating to improve response to treatment, as perspective to be tested in the ensuing studies.

No abstract