Platinum-based drugs are an important component of chemotherapy, particularly in hormone-dependent cancers such as prostate, breast and ovarian.
Satraplatin is a new, third generation, platinum drug, originally discovered by Johnson Matthey and now being developed by GPC Biotech.1 The orally available drug has higher lipophilicity than cisplatin, and its activity is thought to result from its ability to bind to, and crosslink, DNA. Importantly, while satraplatin – DNA adducts are repaired via the nucleotide excision pathway, the DNA mismatch system that repairs both cisplatin and carboplatin adducts does not work here.
In a Phase II trial in metastatic breast cancer, 40 naïve and experienced patients were given doses of 80mg/m2 on the first five days of a 21-day cycle.2 If it was tolerated for two cycles, the dose was increased to 100mg/m2 for subsequent cycles. Of the 31 evaluable patients, there were two partial responses, and four achieved stable disease for at least six months. The median survival was 15 months, and the median progression-free survival 2.7 months. The most common adverse events were neutropenia and thrombocytopenia, plus nausea and vomiting. The conclusion was that while it has limited activity as a single agent in metastatic breast cancer, it could be effective in combination with other agents.
A Phase III trial has been carried out in 950 patients with metastatic, castrate refractory prostate cancer who had progressed after one prior chemotherapy regimen. Subjects were given 80mg/m2 of satraplatin or placebo on days 1 to 5 of a 25-day cycle, plus 5mg prednisone.3 A 33% reduction was seen in the risk of progression or death in the satraplatin group compared with placebo, regardless of whether they had previously been treated with docetaxel, although there was no difference in overall survival between the two groups. However, it did significantly reduce time to pain progression compared with placebo, and was generally well tolerated. Trials continue, with the drug given in combination with other drug therapies.
References
1. A.R. Khokhar et al. J. Inorg. Biochem. 1993, 51, 677
2. J.W. Smith et al. Breast Cancer Res. Treat. 2009, 118, 361
3. C.N. Sternberg et al. J. Clin. Oncol. 2009, 27, 5431
