Abstract
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/m2 days 1 and 8 plus satraplatin 60 mg/m2 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.
Highlights
The target accrual was 380 patients, only 50 patients were enrolled when the study was terminated early due to a company decision. This trial demonstrated that the combination of satraplatin and prednisone resulted in a significant increase in PSA response compared to prednisone alone (33 vs 9%; P = 0.046), and improvement in progression-free survival (PFS; 5.2 vs 2.5 months; P = 0.023; Sternberg et al, 2005)
The arsenal of novel hormonal treatment for patients with castration-resistant prostate cancer (CRPC) has radically changed in recent years
The results of this trial showed that the combination of gemcitabine and satraplatin, in particular given in an every 3 week cycle is feasible and has potential anti-tumor activity
Summary
Satraplatin is a third generation oral platinum complex that has demonstrated activity against several platinum-sensitive and -resistant human tumor cell lines (Twentyman et al, 1992; Kelland et al, 1993; Mellish et al, 1993; Orr et al, 1994; Raynaud et al, 1996).Preclinical and clinical studies have shown that satraplatin can potentiate the effects of radiotherapy (Van de Vaart et al, 1997; Amorino et al, 1999, 2000; George et al, 2001). In a phase II trial of satraplatin in 39 chemo-naive patients with progressive castration-resistant prostate cancer (CRPC), 7 of 22 (32%) patients had a PSA response, toxicity was mainly hematologic, with grade 3/4 non-hematologic toxicities including transient increases in aspartate transaminase and bilirubin (Latif et al, 2005). The target accrual was 380 patients, only 50 patients were enrolled when the study was terminated early due to a company decision This trial demonstrated that the combination of satraplatin and prednisone resulted in a significant increase in PSA response compared to prednisone alone (33 vs 9%; P = 0.046), and improvement in progression-free survival (PFS; 5.2 vs 2.5 months; P = 0.023; Sternberg et al, 2005)
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