Is there a role for platinum chemotherapy in the treatment of patients with hormone‐refractory prostate cancer?

Abstract

Docetaxel chemotherapy is the current standard of care for metastatic hormone-refractory prostate cancer (HRPC). Platinum chemotherapy drugs, such as cisplatin and carboplatin, have moderate single-agent activity in HRPC. Next-generation platinum drugs, including satraplatin and oxaliplatin, may have additional activity in the management of HRPC. Furthermore, neuroendocrine differentiation may play a role in disease progression, providing a rationale for platinum-based chemotherapy in the management of HRPC. The authors reviewed the MEDLINE database for reports related to platinum-based chemotherapy in patients with advanced prostate cancer and evaluated studies that reviewed the role of neuroendocrine differentiation in the progression of HRPC. Older studies from the 1970s and 1980s suggested a lack of activity of cisplatin and carboplatin; however, those studies were flawed at least in part by their methods of response assessment. More recent Phase II studies of carboplatin suggested a moderate level of clinical and palliative activity when it was used as a single agent. However, when carboplatin was combined with a taxane and estramustine, high response rates were observed in several recent clinical trials. In addition, a randomized trial suggested that satraplatin plus prednisone improved progression-free survival compared with prednisone alone. For patients who progressed after docetaxel, no standard options existed in the literature that was reviewed. Several preliminary reports suggested that carboplatin and oxaliplatin may have activity as second-line chemotherapy. Platinum chemotherapy drugs historically have been considered inactive in HRPC, although a review of the data suggested otherwise. Carboplatin, in particular, induced very high response rates when it was combined with estramustine and a taxane, but it also appeared to have activity in patients who progressed after docetaxel. Satraplatin plus prednisone is being investigated in a large Phase III trial as second-line chemotherapy for HRPC. Targeting neuroendocrine cells may provide a new therapeutic approach to HRPC.

Current Status and Future Prospects for Satraplatin, an Oral Platinum Analogue

“…Until recently, HRPC has been widely considered resistant to chemotherapy, including cisplatin and carboplatin (46), although these studies were limited by traditional measures of radiographic response for treatment assessment (47). Two recent landmark trials, however, showed that docetaxel-based chemotherapy afforded statistically significant improvements in overall survival, prostate-specific antigen (PSA) response, pain relief, and quality of life, setting a new standard of care for HRPC patients (48,49).…”

ECF chemotherapy for liver metastases due to castration-resistant prostate cancer

“…Use of capecitabine instead of infusional 5-fluorouracil (ECX) has been at least as effective as ECF in esophagogastric cancer. 15 Oh and colleagues 16 reviewed the use of platinum-based chemotherapy in CRPC and identified objective response rates ranging from 45% to 65% with combinations of estramustine, carboplatin, and either paclitaxel or docetaxel in 6 phase II trials. In a subsequent report studying docetaxel plus carboplatin, the objective response rate was 25% in chemonaive patients who also received with estramustine, and 8% in patients progressing despite docetaxel.…”

The evolving biology and treatment of prostate cancer

“…A phase III trial of satraplatin, an oral platinum that inhibits replication through the formation of DNA adducts, has demonstrated activity as a second line chemotherapy for patients with androgen-independent disease (77). The increased understanding of the relationship between DNA and chromatin structural proteins has led to the development of histone deacetylase inhibitors such as suberoylanilide hydroxamic acid (vorinostat), which interferes with chromatin unfolding and subsequent gene activation (78).…”