At the 2007 meeting of the American Society of Clinical Oncology (ASCO) in June, there were three studies presented which suggest that  picoplatin, a third generation platinum compound, may have significant activity for treatment of refractory cancers.

Picoplatin is an oral or intravenous drug which was designed to overcome platinum resistance and to be less toxic than Platinol® (cisplatin) or Paraplatin® (carboplatin). In November of 2005, picoplatin was granted orphan drug status for the treatment of small-cell lung cancer (SCLC) by the US Food and Drug Administration (FDA). Picoplatin also appears to have activity in patients with hormone-refractory prostate cancer (HRPC). In a study presented at the ASCO 2002 meeting, 11 of 22 patients with HRPC had a partial response or stable disease following iv picoplatin treatment.[1] Picoplatin was found to have minimal activity as a single agent in patients with metastatic breast cancer.[2]

In the SCLC trial presented at ASCO 2007, researchers from the US and Russia reported that picoplatin (Poniard Pharmaceuticals) treatment resulted in disease control in almost half of platinum-resistant SCLC patients.[3] This trial included 84 patients with resistant or refractory SCLC treated with iv picoplatin. The overall response rate was 9% with 38% having stable disease. Median progression-free survival was 10 weeks and the median survival was 27 weeks. Toxicities appeared to be moderate. These researchers are currently performing a Phase 3 trial (S-PEAR) which compares picoplatin to best supportive care in patients with refractory or resistant SCLC.

The colorectal study was a Phase I study combining picoplatin with 5-FU and leucovorin as initial therapy for patients with metastatic colorectal cancer.[4] The researchers reported that picoplatin has been administered in doses up to 90 mg/m2 every 2 weeks or 180 mg/m2 every 4 weeks, but the maximum tolerated dose (MTD) has not yet been determined. A randomized Phase II trial will commence once the dose finding study is over.

The third study reported at ASCO 2007, was a Phase I-II study of Taxotere, prednisone and picoplatin in patients with HRPC.[5] These researchers have treated 26 patients to date and the regimen appears to be well tolerated with hematologic toxicity being the major side effect. A Phase II study has been planned and will begin when the MTD of picoplatin has been identified.

Comments: These are very early studies but suggest that picoplatin in combination with other agents may prove to be an active drug for the treatment of several cancers. The continued development of platinum compounds that are less toxic and possibly more effective than first generation Platinol and Paraplatin is of major interest.

References:

1] Tyrrell C, Bullard S, Barber J, et al. ZD0473 open-label Phase II study in patients with metastatic hormone-refractory prostate cancer. Journal of Clinical Oncology. 2002; 21:Abstract # 2468.

Related news:

Satraplatin Effective for Treatment of Hormone Refractory Prostate Cancer (6/15/2007)

Orphan-Drug Designation for Picoplatin (11/16/2005)