For more than a decade, oncologists using cytotoxic chemotherapy to treat patients with advanced metastatic castration-resistant prostate cancer (mCRPC) have relied on the sequential use of single agent taxanes such as docetaxel and cabazitaxel.
For example, docetaxel is commonly used as the “first-line” therapy, while cabazitaxel is used as the “second-line” therapy. A role for combination therapy using two or more chemotherapy agents at the same time has not been well studied. However, results of a clinical trial presented at the American Society of Clinical Oncology meeting by researchers at The University of Texas MD Anderson Cancer Centre may change the perspective on a role for combination chemotherapy in advanced disease.
The study compared the effectiveness of cabazitaxel alone versus cabazitaxel combined with carboplatin – a type of platinum chemotherapy – in patients with mCRPC. To date, 160 men have been randomised to treatment with either the single or dual chemotherapy drug regimen. Each patient received up to 10 cycles of chemotherapy.
To monitor the effects of treatment, MD Anderson researchers tracked several variables including Progression Free Survival (PFS), as well as changes in blood levels of prostate-specific antigen (PSA) and bone-specific alkaline phosphatase (BAP, a marker of prostate cancer in bone cells). In addition, safety and toxicity were monitored for both patient groups.
Cabazitaxel – carboplatin combo demonstrated significantly longer Progression Free Survival versus single agent chemotherapy
Analysis and comparison of the data demonstrated that median PFS was significantly longer for patients receiving combination versus single agent chemotherapy (6.7 months vs 4.4 months, respectively). Furthermore, reductions in both PSA and BAP were greater for the combination therapy group. PSA reductions greater than 50% occurred 60% of the time with combined chemotherapy vs. 44% with the single drug. PSA reductions greater than 90% occurred 28% of the time with two chemotherapy drugs vs. 20% with one. In addition, BAP reductions greater than 50% for combination vs. single drug were 63% and 25% respectively.
Side effects, such as fatigue, anemia and neutropenia were comparable for both the single-drug regimen and two-drug regimen. In addition, there were no significant toxicity events.
“We believe cabazitaxel – carboplatin combination chemotherapy may become the clinical standard for advanced prostate cancer once additional safety, efficacy and overall survival data is generated,” explained Paul Corn, M.D., Ph.D., an associate professor of genitourinary medical oncology at MD Anderson. “Dr Ana Aparicio’s lab is currently developing tumour-specific biomarkers to identity patients with an aggressive variant of prostate cancer most likely to benefit from this approach.”
The study was funded by Sanofi.
