Oral Platinum Analogue Looks Good

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Satraplatin may prolong progression-free survival in men with hormone-refractory prostate cancer.

 

NEW YORK—Satraplatin, the first oral platinum analogue, is among the more promising second-line treatments for hormone-refractory prostate cancer (HRPC), a researcher said here at the 2006 Chemotherapy Foundation Symposium.

 

No agent is approved as second-line chemotherapy for HRPC, Oliver Sartor, MD, told listeners at the Chemotherapy Foundation Symposium here. “There is an unmet need when primary chemotherapy fails. First-line chemotherapy for advanced prostate cancer is now being used more widely and earlier in the disease course, but second-line therapies are empiric and usually symptom-directed.” Dr. Sartor is at the Lank Center for Genitourinary Oncology at Dana Farber Cancer Institute and Harvard Medical School in Boston.

 

Current chemotherapy options for HRPC include estramustine phosphate, mitoxantrone, and docetaxel. Docetaxel is the only chemotherapy agent to show a survival advantage in Phase III trials. Other investigational agents for this disease include satraplatin, epothilones, and histone deacetylase inhibitors.

 

Rationale

Platinum compounds have activity in HRPC even in patients who fail treatment with taxanes, Dr. Sartor noted. Satraplatin has been studied in about 1,500 patients. The drug's safety profile improves upon that of cisplatin and is in some ways similar to that of carboplatin. Satraplatin has demonstrated activity in HRPC in the European Organization for Research and Treatment of Cancer (EORTC) trial; the drug also has activity in other platinum-sensitive tumors, including ovarian cancer and small-cell lung cancer.

 

Three phase III and two phase II clinical trials of satraplatin as a treatment for prostate cancer have been conducted. The largest is the on-going phase III Satraplatin and Prednisone Against Refractory Can-cer (SPARC) trial, which compares satraplatin plus prednisone with prednisone alone as second-line treatment of HRPC in 950 patients.

 

In 2005, a phase III EORTC trial showed that satraplatin plus prednisone prolonged progression-

free and overall survival by about three months compared with prednisone alone. Median progression-free survival was 5.3 months for satraplatin plus prednisone versus 2.5 months for prednisone monotherapy (Oncology 2005;68:2-9). Overall survival of patients receiving satraplatin plus prednisone was a median of 14.9 months, compared with 11.9 months with prednisone alone. Of the 27 patients treat-ed with satraplatin, only four had grade 4 toxicity (neutropenia). The satraplatin regimen was considered to have good tolerability.

 

SPARC trial

In the SPARC trial, patients are randomized to one of two groups. In one group, patients receive satra-platin 80 mg/m2 for five days every five weeks in addition to predni-sone 5 mg twice daily, plus granisetron 1 mg twice daily for five days every five weeks. In the other group, patients receive prednisone 5 mg twice daily plus placebo and granisetron 1 mg twice daily for five days every five weeks. Study participants have metastatic prostate cancer that had progressed after one prior cytotoxic regimen. Other inclusion criteria include ECOG Performance Status of 2 or less; life expectancy greater than three months; prior surgical or medical castration; and adequate bone marrow, hepatic, and renal functions.

 

Patients are excluded if they have GI conditions that affect absorption of oral drugs, disease with contraindications to steroids, or brain metastases. Treatment is continued until disease progression, intolerable toxicity, or patient withdrawal of consent. Accrual was completed in December 2005.

 

According to an intent-to-treat analysis, satraplatin achieved a 40% reduction in risk of progression-free survival (independent of whether patients had been previously treated with docetaxel). Survival data is still immature with results anticipatedin fall 2007.

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