Picoplatin pharmacokinetics and chemotherapy of non-small cell lung cancer.

Abstract

INTRODUCTION:

Picoplatin was developed as platinum coordination complex to overcome development of resistance, through conjugation to thioles, by the introduction of a methyl-pyridine moiety into the cisplatin parent structure. Pharmacokinetic parameters of the drug, after intravenous and oral application, were studied in solid tumors and clinical Phase I - III trials performed, in particular in NSCLC and small cell lung cancer (SCLC). Results showed low clinical activity of picoplatin.

AREAS COVERED:

This article presents an overview of the pharmacokinetic assessments of picoplatin in lung cancer. Specifically, the authors address the relationship between disposition and clinical activity of the drug.

EXPERT OPINION:

Picoplatin failed to overcome resistance to platinum compounds in lung cancer to achieve significant improved survival of most patients. Even highest doses of the drug reaching 150 m/m² given intravenously every 3 weeks were not sufficient to achieve better response than existing chemotherapeutics and the oral bioavailability of a dose of 200 - 400 mg corresponded only to 80 mg/m² iv. Picoplatin therefore seem to be quite ineffective. Picoplatin is expected to overcome tumor resistance in cases which overexpress thiol-conjugating pathways; however, this was not proved in clinical trials. To conclude, this blocked platinum complex is not able to reverse cisplatin resistance to a significant extent in vivo and its mechanisms and kinetics and of DNA damage failed to produce significant clinical results compared to second-line standard therapy for lung cancer.

• Authors: Gerhard Hamilton, Ulrike Olszewski
• Journal: Expert opinion on drug metabolism & toxicology (Expert Opin Drug Metab Toxicol) Vol. 9 Issue 10 Pg. 1381-90 (Oct 2013) ISSN: 1744-7607 [Electronic] England
• PMID: 23829480 (Publication Type: Journal Article, Review)

Chemical References

• Organoplatinum Compounds
• Platinum Compounds
• amminedichloro(2-methylpyridine)platinum(II)
• Cisplatin

Topics

• Administration, Oral
• Animals
• Biological Availability
• Carcinoma, Non-Small-Cell Lung (drug therapy)
• Cell Line, Tumor
• Cisplatin (administration & dosage, pharmacokinetics)
• Clinical Trials, Phase I as Topic
• Clinical Trials, Phase II as Topic
• Disease Models, Animal
• Drug Evaluation, Preclinical
• Drug Resistance, Neoplasm (drug effects)
• Humans
• Lung Neoplasms (drug therapy)
• Organoplatinum Compounds (administration & dosage, pharmacokinetics)
• Platinum Compounds (pharmacokinetics)
• Randomized Controlled Trials as Topic