Background: Site-specific delivery of anti-cancer therapeutics is paramount for both reducing
nonspecific toxicities and increasing efficacy of chemotherapeutic agents. Due to their small
molecular size and nonspecific mechanisms of action, most conventional chemotherapies result
in significant toxicities that limit the effectiveness of treatment and reduce the overall
quality of life for cancer patients. Encapsulation of these toxic agents inside lipid-based
carrier systems (so-called liposomes) results in passive targeting of the compounds to solid
tumors. The preferential delivery of liposomal drugs to solid tumors is mostly due to altered
barrier-properties of tumor-associated vessels. This results in both an improved delivery and
at the same time a significantly milder toxicity profile. Recently, the specificity of
delivery was further increased by attaching monoclonal antibodies or antibody fragments to
the surface of liposomes (=immunoliposomes, antibody-linked nanoparticles). Antibody-coated
immunoliposomes attach more selectively to antigens expressed on the target cells and they
are internalized more efficiently. Furthermore, there is evidence that drug resistance, a
major challenge in cancer treatment, may be overcome by such delivery systems. A logical and
accessible target, such as EGFR, is overexpressed on a variety of primary human cancer cells
and it is involved in signaling pathways that contribute both to tumor initiation and tumor
progression. Recently, the investigators have tested immunoliposomes against the epidermal
growth factor receptor (EGFR) in a preclinical setting. Based on the preclinical results we
have initiated this phase I clinical trial.
Study hypothesis: The investigators hypothesize that anti-EGFR-immunoliposomes selectively
deliver cytotoxic compounds to EGFR-overexpressing tumors cells. Specific delivery is
supposed to increase efficacy while reducing side-effects of the compound. The primary
objective of this phase 1 trial is the determination of the maximum tolerated dose (MTD) for
future phase 2 trials of this nanoparticle.