Anatomical Targeting of Anticancer Drugs to Solid Tumors Using Specific Administration Routes: Review

Abstract

Despite remarkable recent progress in developing anti-cancer agents, outcomes of patients with solid tumors remain unsatisfactory. In general, anti-cancer drugs are systemically administered through peripheral veins and delivered throughout the body. The major problem with systemic chemotherapy is insufficient uptake of intravenous (IV) drugs by targeted tumor tissue. Although dose escalation and treatment intensification have been attempted in order to increase regional concentrations of anti-tumor drugs, these approaches have produced only marginal benefits in terms of patient outcomes, while often damaging healthy organs. To overcome this problem, local administration of anti-cancer agents can yield markedly higher drug concentrations in tumor tissue with less systemic toxicity. This strategy is most commonly used for liver and brain tumors, as well as pleural or peritoneal malignancies. Although the concept is theoretically reasonable, survival benefits are still limited. This review summarizes clinical results and problems and discusses future directions of regional cancer therapy with local administration of chemotherapeutants.

Intratumoral Injection of Large Surface Area Microparticle Taxanes in Carcinomas Increases Immune Effector Cell Concentrations, Checkpoint Expression, and Synergy with Checkpoint Inhibitors: A Review of Preclinical and Clinical Studies

“…IT LSAM-PTX- and LSAM-DTX-induced tumoricidal responses are accompanied by favorable immunomodulation in the tumor and/or peripheral blood, including increased immune effector cells from both innate and adaptive systems, increased checkpoint expression, and decreased immune suppressor cells. Development of LSAM-PTX and LSAM-DTX together with advances in minimally invasive procedures for local drug delivery allow for immune priming of solid tumors virtually anywhere in the body [ 8 ] to increase response to immune checkpoint inhibitors without stacking toxicity. Long-term safety studies have not yet been performed.…”

“…Direct intratumoral (IT) treatment of solid tumors with chemotherapy has the potential to overcome many limitations of conventional intravenous (IV) administration including severe toxicities resulting from systemic distribution [ 7 , 8 ]. Locally intensive therapies for solid tumors would likely improve treatment efficacy by inducing continuous exposure of tumor cells to therapeutic drug levels over multiple tumor cell-divisions [ 9 , 10 ]).…”