Oral agent shows efficacy as second-line prostate cancer therapy

New York-Satraplatin, an oral platinum analog in late-stage development as second-line chemotherapy for hormone-refractory prostate cancer, has shown encouraging results in phase III trials, said Oliver Sartor, MD, associate professor of medicine at the Lank Center for Genitourinary Oncology at Dana Farber Cancer Institute, Boston. Dr. Sartor, who reviewed phase III results of the drug at the recent Chemotherapy Foundation Symposium here, said satraplatin is one of the most promising new agents under study for hormone-refractory disease.

No agent is currently FDA-approved as second-line chemotherapy for hormone-refractory prostate cancer. As chemotherapy is being used earlier in the course of disease, there is an unmet need for second-line chemotherapy when cancer progresses on first-line treatment, Dr. Sartor explained. At present, second-line therapy is primarily empiric and directed to symptoms.

Although several chemotherapy agents are used to treat hormone-refractory prostate cancer, including estramustine phosphate (Emcyt), mitoxantrone (Novantrone), and docetaxel (Taxotere), docetaxel is the only drug to show a survival advantage in randomized, controlled trials. Satraplatin is one of several newer agents, among them epithilones and histone deacetylase inhibitors, under investigation for this indication.

Several platinums are now FDA approved. Cisplatin (Platinol) was widely used for a number of years, but has serious toxicities in elderly patients. Carboplatin (Paraplatin), the next platinum compound to be introduced, has an improved safety profile. Satraplatin's safety profile is similar to that of carboplatin, but unlike cisplatin and carboplatin, the drug is given orally.

Current trials

About 1,500 patients have been included in the development program for satraplatin. It includes two phase II trials and three phase III trials. In EORTC 30972, a phase III trial, satraplatin plus prednisone demonstrated good tolerability and prolonged progression-free and overall survival versus prednisone alone. Median progression-free survival was 5.3 months for satraplatin plus prednisone versus 2.5 for prednisone alone (Oncology 2005; 68:2-9). Overall survival was a median of 14.9 months with satraplatin plus prednisone versus 11.9 months with prednisone alone. Of the 27 patients treated with satraplatin, only four had a grade 4 toxicity (neutropenia).

Satraplatin and Prednisone Against Refractory Cancer (SPARC) is the largest study in satraplatin's development program. The ongoing, multinational, multicenter study has enrolled 950 patients with hormone-refractory prostate cancer who progressed on one prior cytotoxic regimen. Patients are treated with satraplatin, 80 mg/m² , on days 1 to 4 every 5 weeks, plus prednisone 5 mg twice daily, plus growth factor support with granisetron (Kytril), 1 mg twice daily on days 1 to 5 every 5 weeks; or with prednisone and placebo satraplatin and granisetron. Treatment is continued until disease progression, intolerable toxicity, or patient withdrawal of consent.

Patients enrolled in the trial are classified as ECOG performance status ≤2, have a life expectancy greater than 3 months, underwent prior surgical or medical castration, and have adequate bone marrow, hepatic, and renal function. Gastrointestinal conditions that affect absorption of oral drugs, disease with contraindications to steroids, and brain metastases are grounds for exclusion.

In an intent-to-treat analysis, satraplatin achieved a 40% reduction in risk of progression-free survival, which was the pre-determined primary endpoint (hazard ratio: 0.6, 95% confidence interval: 0.5-0.7, p<.00001) and was well tolerated. These results were independent of previous docetaxel treatment. Progression-free survival at various intervals was: 50th percentile, 11 versus 9.7 weeks, respectively (13% improvement); 75th percentile, 36 weeks versus 19 weeks, respectively (89% improvement); 6 months, 30% versus 17% non-progression, respectively; 12 months, 16% versus 7% non-progression, respectively.

"Thus, it is clear that progression-free survival is enhanced in satraplatin-treated patients," Dr. Sartor said. "Given the significant treatment challenges in this patient population, these results are clinically significant."