A hindsight reflection on the clinical studies of poly(l-glutamic acid)-paclitaxel.

Chemotherapy for cancer treatment is limited by the excessive toxicity to normal tissues. The design of chemodrug-loaded nanoformulations provides a unique approach to improve the treatment efficacy while minimizing toxicity. Despite the numerous publications of nanomedicine for the last several decades, however, only a small fraction of the developed nanoformulations have entered clinical trials, with even fewer being approved for clinical application. Poly(l-glutamic acid)-paclitaxel (PG-TXL) belongs to the few formulations that reached phase III clinical trials. Unfortunately, the development of PG-TXL stopped in 2016 due to the inability to show significant improvement over current standard care. This review will provide an overview of the preclinical and clinical evaluations of PG-TXL, and discuss lessons to be learned from this ordeal. The precise identification of suitable patients for clinical trial studies, deep understanding of the mechanisms of action, and an effective academic-industry partnership throughout all phases of drug development are important for the successful bench-to-bedside translation of new nanoformulations. This article is categorized under: Implantable Materials and Surgical Technologies > Nanomaterials and Implants Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Biology-Inspired Nanomaterials > Peptide-Based Structures.