Satraplatin: leading the new generation of oral platinum agents

Abstract

Background In recent years, JM-216/satraplatin (GPC Biotech, Inc.) has emerged as a novel oral platinum analogue with a better toxicity profile than cisplatin. Since satraplatin is more hydrophobic than cisplatin or oxaliplatin, it appears to demonstrate efficacy in cisplatin-resistant cell lines. The preclinical and clinical evaluation of satraplatin stimulated this review of the pharmacology and clinical trial data of this agent. Methods A literature review was conducted in the MEDLINE database from 1985 to present using the keywords ‘satraplatin’ or ‘JM-216’. The abstracts regarding satraplatin reported at the 2007 – 2009 American Society of Clinical Oncology meetings were also reviewed. Results/conclusion Satraplatin has a favorable toxicity profile, and appears to have clinical activity against a variety of malignancies such as breast, prostate and lung cancer. The oral route of administration and the intermittent schedule makes it very convenient for clinical use. Despite this, a FDA-approved indication has not yet been achieved. The only Phase III trial with satraplatin was conducted in pretreated metastatic castrate-resistant prostate cancer (CRPC), revealing an improvement in progression-free survival but no overall survival benefit. Future development would have to include designing trials in docetaxel-refractory metastatic CRPC, or in other malignancies where cisplatin is of benefit.

Fourier Transform Infrared (FTIR) spectroscopy to monitor the cellular impact of newly synthesized platinum derivatives

“…For a brief period, the economic cost of these unsuccessful efforts retarded further efforts to develop new agents (3). Despite these challenges, however, two new exciting platinum agents have been brought to Phase III trials: satraplatin for hormone-refractory prostate cancer (3,42) and picoplatin for small-cell lung cancer (3). If successful, they may inspire a new effort to bring betterdesigned platinum agents to market (3).…”

“…Owing to the nature of the platinum atom, which is a highly reactive Lewis acid, numerous cellular components are prone to bind the complexes, including nucleic acids (DNA and RNA), proteins and phospholipids (45). Despite this large variety of targets, however, it is commonly admitted that DNA is the most relevant biological structure responsible for their anticancer effects (3,(38)(39)(40)(41)(42)45), which has been proven by the analysis of the cellular responses triggered by platinum complex treatment, mainly in terms of protein expression (14,(46)(47)(48). Upon binding of the complexes, several peptides are recruited to recognize the DNA lesions and trigger apoptosis, as well as to repair the nucleic acid structure and allow cancer cell survival (46)(47)(48).…”

Drug Development: Portals of Discovery

“…The accumulated evidence indicates clearly that satraplatin belongs to the former, a newer version of an established agent (46). In the case of satraplatin, the established agents were cisplatin and carboplatin.…”

Multivariant Crystallization of Tetraplatin Precursors from Solutions Containing 1,2-C6H10(NH3)2 2+ and [PtCl6]2– Ions

“…Today, the compound is one of the few platinum drugs, approved for clinical application [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]. Tetraplatin is similar to cisplatin on efficiency but has less nephrotoxicity [19].…”