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BACKGROUND
For men with advanced castration-resistant prostate cancer (CRPC),
several treatment options are available, including androgen receptor
(AR) pathway inhibitors (abiraterone acetate, enzalutamide), taxanes
(docetaxel, cabazitaxel) and the radionuclide (radium-223). However,
cross-resistance is a clinically relevant problem. Platinum
compounds have been tested in a number of clinical trials in
molecularly unselected prostate cancer patients. Advances in CRPC
molecular profiling have shown that a significant proportion of
patients harbour DNA repair defects, which may serve as predictive
markers for sensitivity to platinum agents.
OBJECTIVE
To systematically identify and analyse clinical trials that have
evaluated platinum agents in advanced prostate cancer patients.
METHODS
PubMed was searched to identify published clinical trials of
platinum agents in advanced prostate cancer. The PRIMSA statement
was followed for the systematic review process. Identified trials
are analysed for study design, statistical plan, assessments of
anti-tumour activity and the potential value of predictive
biomarkers.
RESULTS
A total of 163 references were identified by the literature search
and 72 publications that met the selection criteria were included in
this review; of these 33 used carboplatin, 27 cisplatin, 6
satraplatin, 4 oxaliplatin and 2 other platinum compounds. Overall,
anti-tumour activity varies in the range of 10%-40% for objective
response and 20%-70% for PSA decline ≥50%. Response seemed
highest for the combinations of carboplatin with taxanes or
oxaliplatin with gemcitabine. The interpretation of the clinical
data is limited by differences in response criteria used and patient
populations studied.
CONCLUSION
Platinum compounds have moderate anti-tumour activity in molecularly
unselected patients with advanced prostate cancer. Translational
evidence of DNA repair deficiency should be leveraged in future
studies to select prostate cancer patients most likely to benefit
from platinum-based therapy.
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