Advancements in platinum chemotherapy for metastatic castration-resistant prostate cancer: Insights and perspectives.

ABSTRACT

Despite improvements in survival, metastatic castration-resistant prostate cancer (mCRPC) remains a significant clinical challenge. While taxanes, new hormonal agents, radiopharmaceuticals, and PARP inhibitors offer valuable treatment options, this review explores the potential of platinum chemotherapies (carboplatin, cisplatin, and oxaliplatin) as alternative choices. Existing research demonstrates promising preliminary results for platinum-based therapies in mCRPC showing PSA response rates (7.7-95 %) and improved overall survival (8-26.6 months). However, chemotherapy-related cytopenias are a frequent side effect. Further research is underway to evaluate the efficacy of platinum regimens against specific mCRPC histopathological variants, particularly aggressive subtypes where the carboplatin and cabazitaxel combination is already recommended. The unique DNA-targeting action of platinum therapy holds promise for patients with deficient DNA repair (dDDR), especially those with BRCA mutations. This potential is supported by both preclinical and ongoing clinical research. Given the limited success of immunotherapy in mCRPC, researchers are exploring the potential for platinum therapies to enhance its efficacy. Additionally, trials are investigating the synergy of combining platinum therapy with both immunotherapy and PARP inhibitors. Further exploration into the effectiveness of platinum therapies in specific mCRPC subpopulations, particularly those with dDDR, is crucial for optimizing their future use. In conclusion, this review highlights the promising potential of platinum-based chemotherapy as a valuable treatment option for mCRPC. While current evidence is encouraging, ongoing research is essential to further optimize its efficacy, identify optimal combinations with other therapies, and better understand its impact on specific mCRPC subpopulations.