Health and Prostate

Satraplatin (GPC Biotech’s JM-216) is a third-generation oral platinum agent. Satraplatin reentered Phase III development for second-line treatment of hormone-refractory CaP in September 2003; a previous Phase III trial was halted early by the previous developer, Bristol-Myers Squibb. The ongoing Phase III trial, whose primary endpoint is time to disease progression, is known as SPARC (Satraplatin and Prednisone Against Refractory Cancer). In 2003, the FDA granted satraplatin fast-track status, and in early 2004, the Phase III trial was extended to Europe.

A Phase I study protocol that will combine satraplatin with docetaxel to treat various tumor types is in preparation. Because satraplatin is orally administered and does not require hydration to prevent renal toxicity, home administration is possible. In animal models, satraplatin has demonstrated efficacy in tumors that are resistant to platinum agents, possibly as a result of increased lipophilicity, allowing for more passive uptake of the platinum complexes by cancer cells.

At ASCO 2003, investigators presented findings from the first 50 patients treated in the original Phase III trial in patients with hormone-refractory CaP. The trial was initiated by Bristol-Myers Squibb in 1998, and accrual was halted when Bristol-Myers Squibb discontinued development of the agent, although the patients were allowed to continue treatment on a compassionate-use basis. Patients received 100 mg / m² satraplatin for five days plus 10 mg prednisone orally twice daily, or prednisone alone. A greater than 50% decline in PSA was seen in 8.7% of patients in the prednisone arm and in 33.3% in the satraplatin / prednisone arm (p = 0.046). Toxicity was minimal in both arms; one patient in each arm died from stomach perforation, probably related to prednisone. Median survival was 12 months in the prednisone arm and 15 months in the combination arm. The median time to disease progression was 5.2 months for the satraplatin arm versus 2.5 months for the control arm. At 6 months, 41% of patients in the satraplatin arm were progression-free versus 22% in the control arm; at 12 months, 70% of patients in the satraplatin arm were alive versus 48% in the control arm.

A Phase II trial treated 39 patients with hormone-refractory CaP with 120 mg / m² / day satraplatin for five of 28 days. Of nine evaluable patients with measurable disease, one had a partial response and six had stable disease. Seven patients had PSA reductions of greater than 50% for a duration of 28 days; six had reductions of greater than 80%. The principle toxicities were myelosuppression, nausea, and fatigue.

In Phase I trials, neutropenia was the dose-limiting toxicity. Other common toxicities include thrombocytopenia, severe vomiting, diarrhea, and fever. No nephro-, oto-, or neurotoxicities have been reported. Because of irregular pharmacokinetics in this trial, researchers introduced dose fractionation in subsequent trials.