Combination Drug Delivery Approaches in Metastatic Breast Cancer

Abstract

Disseminated metastatic breast cancer needs aggressive treatment due to its reduced response to anticancer treatment and hence low survival and quality of life. Although in theory a combination drug therapy has advantages over single-agent therapy, no appreciable survival enhancement is generally reported whereas increased toxicity is frequently seen in combination treatment especially in chemotherapy. Currently used combination treatments in metastatic breast cancer will be discussed with their challenges leading to the introduction of novel combination anticancer drug delivery systems that aim to overcome these challenges. Widely studied drug delivery systems such as liposomes, dendrimers, polymeric nanoparticles, and water-soluble polymers can concurrently carry multiple anticancer drugs in one platform. These carriers can provide improved target specificity achieved by passive and/or active targeting mechanisms.

Evaluation of Docetaxel vs. Tamoxifen in Combined Therapies Based on Overall Survival Rate (OSR) Endpoint among Female Breast Cancer Patients

“…Neutropenia was found to be the leading toxicity with combined therapies of Docetaxel. Similar safety analysis such as one presented by Lee and Nan [12] confirmed that severe hematological toxicity such as neutropenia was common with Docetaxel combined regimens among breast cancer patients.…”

“Combo” nanomedicine: Co-delivery of multi-modal therapeutics for efficient, targeted, and safe cancer therapy

“…Confirming and understanding a truly synergistic therapy regimen requires in-depth evaluation of the cancer-driven pathways and their individual components. Ratios of therapeutic agents must be optimized based upon quantitated synergy with each other [145]. Three different drug combinations taken from various drug classes (irinotecan/floxuridine, cytarabine/daunorubicin, and cisplatin/daunorubicin) were evaluated for ratio-dependent synergy.…”

Drug delivery approaches for breast cancer

“…Numerous polymer-drug conjugates, such as poly(d,l-lactide-coglycolide) (PLGA), PEG, dextran, and N-(2-hydroxypropyl) methacrylamide (HPMA), have been tested in drug delivery research. 24 Chemotherapeutic drugs like paclitaxel, doxorubicin, camptothecins, and platinates have been clinically tested in drug conjugates for multiple cancers. It has been shown that polymeric NPs have a higher loading capacity for poorly water-soluble drugs, more stability, and more physicochemical properties (solubility, stability) compared to liposomes.…”

“…Their study on targeting HER-2 receptors via extracellular (via TRZ binding) and intracellular (via PKI-166 binding) kinase domains suggested the synergistic effect from a drug conjugate delivery system for anticancer activity. 24 Therefore, a novel drug delivery system using a polymer with different mechanisms of action can bring forth a promising targeted therapy to overcome the limitations of the individual drug.…”