ProLindac (AP5346): a review of the development of an HPMA DACH platinum Polymer Therapeutic.

Abstract

ProLindac (AP5346) is DACH (diaminocyclohexane) platinum polymer prodrug currently in phase II clinical development. It uses a 25 kDa polymer delivery vehicle based on hydroxypropylmethacrylamide (HPMA) to target the active form of the approved drug oxaliplatin to tumors. The pH-sensitive linker that binds platinum to the polymer releases platinum more rapidly in low pH environments, as found typically in many tumors. This review summarizes the development of ProLindac to date, including preclinical efficacy studies, the phase I monotherapy clinical study in patients with solid tumors, and the phase I/II monotherapy study in patients with recurrent ovarian cancer. Both preclinical and clinical study data indicate that ProLindac exhibits efficacy at least equal to, and likely superior to oxaliplatin, while demonstrating excellent tolerability. Additional clinical studies of ProLindac used in combination with other chemotherapeutic agents are planned.

• Authors: David P Nowotnik, Esteban Cvitkovic
• Journal: Advanced drug delivery reviews (Adv Drug Deliv Rev) Vol. 61 Issue 13 Pg. 1214-9 (Nov 12 2009) ISSN: 1872-8294 [Electronic] Netherlands
• PMID: 19671439 (Publication Type: Comparative Study, Journal Article, Review)

Chemical References

• Antineoplastic Agents
• Organoplatinum Compounds
• ProLindac
• Oxaliplatin

Topics

• Animals
• Antineoplastic Agents (adverse effects, pharmacology)
• Clinical Trials, Phase I as Topic
• Clinical Trials, Phase II as Topic
• Drug Delivery Systems
• Drug Design
• Humans
• Hydrogen-Ion Concentration
• Neoplasms (drug therapy, physiopathology)
• Organoplatinum Compounds (adverse effects, pharmacology)
• Oxaliplatin