HPMA-based polymer therapeutics improve the efficacy of surgery, of radiotherapy and of chemotherapy combinations.

To assist intravenously administered anticancer agents in achieving proper circulation times and tumor concentrations, and to thereby improve the balance between their efficacy and their toxicity, a large number of drug delivery systems have been designed and evaluated over the years. Clinically relevant examples of such nanometer-sized carrier materials are liposomes, polymers, micelles and antibodies. In the vast majority of cases, however, and especially in patients, nanomedicine formulations are only able to attenuate the toxicity of the conjugated or entrapped chemotherapeutic drug, and they generally fail to improve the efficacy of the intervention. To overcome this shortcoming, and to broaden the clinical applicability of tumor-targeted nanomedicines, in the past 5 years we have developed several concepts for using N-(2-hydroxypropyl)methacrylamide (HPMA)-based polymer therapeutics to enhance the efficacy of combined modality anticancer therapy. Regarding surgery, HPMA copolymers were shown to be able to improve the retention of intratumorally administered chemotherapeutic agents at the pathological site, and to thereby increase their therapeutic index. Regarding radiotherapy, a synergistic interaction was observed, with radiotherapy improving the tumor accumulation of the copolymers, and with copolymers improving both the efficacy and the tolerability of radiochemotherapy. Futhermore, regarding chemotherapy combinations, we have for the first time provided in vivo evidence showing that passively tumor-targeted polymeric drug carriers can be used to deliver two different drugs to tumors simultaneously. Based on these findings, and on the fact that the concepts developed are considered to be broadly applicable, we conclude that nanomedicine formulations are highly suitable systems for improving the efficacy of combined modality anticancer therapy.