Platinum-based drugs: A possible strategy when other treatments stop working

This review analyzed platinum-based drugs in the treatment of advanced castration-resistant prostate cancer. While platinum-based drugs were often associated with various side effects, researchers reported moderate to good treatment effectivity in managing advanced prostate cancer.

Hormone therapy is the standard treatment for advanced prostate cancer. Reducing hormone levels and their effect on cancer cell growth can dramatically improve survival. Over time, many men will stop responding (become resistant) to standard hormone therapy. This is called castration-resistant hormone therapy (CRPC). A number of treatments are available for CRPC. These may include secondary hormone therapies, such as abiraterone acetate (Zytiga) and enzalutamide (Xtandi), taxane-based chemotherapies, such as docetaxel (Taxotere) and cabazitaxel (Jevtana), and radiation therapies, such as radium-233.

A challenge for secondary treatment options is that patients may quickly become resistant to these new agents as a result of previous therapies (cross-resistance). Platinum-based drugs are currently being investigated as a possible alternative or additive treatment for CRPC. They are a type of chemotherapy that may be able to reduce the number of resistant cells and, therefore, allow treatment to maintain effective. Some platinum-based drugs include carboplatin (Paraplatin), cisplatin (Platinol), satraplatin (Orplatna), and oxaliplatin (Eloxatin). 

The aim of this review was to evaluate platinum-based drugs in the treatment of advanced prostate cancer. A total of 72 separate trials were included in analysis. 33 trials investigated carboplatin. 27 trials investigated cisplatin. 6 trials investigated satraplatin. 4 trials investigated oxaliplatin. The remaining 2 trials investigated other platinum compounds.

The main benefit of treatment with carboplatin alone was reported to be a reduction in pain, an improvement in activities of daily living, and disease control. Carboplatin was particularly effective when combined with taxane-based chemotherapies. One trial noted an average treatment response rate (based on blood tests) of 40%. This was significantly higher compared to non-taxane-based chemotherapy alone (10% treatment response). Another trial reported that carboplatin with a taxane-based chemotherapy led to a significant treatment response in 18% of patients no longer responding to chemotherapy. Of 15 patients not yet treated with hormone therapy, 53% showed a complete response when carboplatin was added to standard hormone therapy. The average time until disease progression was 31 months. Common side effects associated with carboplatin included a change in platelet count and fatigue.

Cisplatin alone was found have a treatment response rate of 36% and a pain response rate of 22%. This was comparable to other chemotherapy agents. One trial reported a response rate of 50% or higher in 48% of men when cisplatin was combined with taxane-based chemotherapy. However, fatigue and weakness were severe. The addition of cisplatin to a type of radiation therapy was reported to be more effective at treating cancer spread to the bone (91% pain control) than radiation therapy alone (63% pain control). Other treatment combinations with cisplatin were associated with a high rate of side effects, including organ damage.

One trial found a 3-months advantage in overall survival (time from treatment until death from any cause) when satraplatin was added to a steroid drug. Another trial found no difference in overall survival, but improved treatment and pain response. One trial reported a response rate of 50% or higher in 50% of men with CRPC when satraplatin was combined with a taxane-based chemotherapy. This combination was generally well-tolerated. Nausea, vomiting, diarrhea, and a change in platelet or red blood cell counts were most reported with satraplatin.

Oxaliplatin was found to be more effective when combined with an antimetabolite (5-fluorouracil, a chemotherapy) compared to oxaliplatin alone. Another trial found that the same drug combination resulted in good treatment response rate (50%) in men with CRPC no longer responding to chemotherapy. A decrease in cancer pain and increase in overall survival was noted in a number trials that combined oxaliplatin with other chemotherapies. Side effects included a change in platelet or red blood cell counts, which were mostly mild to moderate.

Researchers concluded that platinum-based drugs alone or in combination showed moderate to good treatment effectivity in men with CRPC.