An open-label, dose-finding study of the combination of satraplatin and gemcitabine in patients with advanced solid tumors.

PURPOSE: Satraplatin is a third generation oral platinum, which has demonstrated antitumor activity. The aim of this phase I study was to determine the maximum tolerated dose (MTD) of the combination of satraplatin and gemcitabine in patients previously treated with chemotherapy and in patients without prior chemotherapy. PATIENTS AND METHODS: Two separate MTDs were planned in two different patient groups (those with and without prior chemotherapy treatment). Dose escalations were planned in cohorts of three patients. Tumor measurements were obtained every two cycles. Assessment of response was performed according to Response Evaluation Criteria in Solid Tumors (RECIST criteria v.1.0). RESULTS: Thirty subjects were enrolled. A MTD of gemcitabine 1000 mg/m(2) days 1 and 8 plus satraplatin 60 mg/m(2) days 1-3, every 21 days was determined in the prior chemotherapy group. No MTD could be determined for the no prior chemotherapy group treated with this schedule. Five patients completed 12 treatment cycles; 22 serious adverse events (SAE) were observed. Although not an entry criteria, overall confirmed response was observed in 17 (24%) evaluable patients (complete response, CR = 1 and partial response, PR = 3) and in 3/7 (43%) patients with measure prostate cancer lesions. CONCLUSIONS: In this phase Ib study, the combination of satraplatin and gemcitabine demonstrated to be safe and efficacious in particular in patients with prostate cancer.

Multinational, double-blind, phase III study of prednisone and either satraplatin or placebo in patients with castrate-refractory prostate cancer progressing after prior chemotherapy: the SPARC trial.

PURPOSE: This multinational, double-blind, randomized, placebo-controlled, phase III trial assessed the efficacy and tolerability of the oral platinum analog satraplatin in patients with metastatic castrate-refractory prostate cancer (CRPC) experiencing progression after one prior chemotherapy regimen. PATIENTS AND METHODS: Nine hundred fifty patients were randomly assigned (2:1) to receive oral satraplatin (n = 635) 80 mg/m(2) on days 1 to 5 of a 35-day cycle and prednisone 5 mg twice daily or placebo (n = 315) and prednisone 5 mg twice daily. Primary end points were progression-free survival and overall survival (OS). The secondary end point was time to pain progression (TPP). RESULTS: A 33% reduction (hazard ratio [HR] = 0.67; 95% CI, 0.57 to 0.77; P < .001) was observed in the risk of progression or death with satraplatin versus placebo. This effect was maintained irrespective of prior docetaxel treatment. No difference in OS was seen between the satraplatin and placebo arms (HR = 0.98; 95% CI, 0.84 to 1.15; P = .80). Compared with placebo, satraplatin significantly reduced TPP (HR = 0.64; 95% CI, 0.51 to 0.79; P < .001). Satraplatin was generally well tolerated, although myelosuppression and GI disorders occurred more frequently with satraplatin. CONCLUSION: Oral satraplatin delayed progression of disease and pain in patients with metastatic CRPC experiencing progression after initial chemotherapy but did not provide a significant OS benefit. Satraplatin was generally well tolerated. These results suggest activity for satraplatin in patients with CRPC who experience progression after initial chemotherapy.