ORLANDO—Researchers have developed a novel combination therapy that may help improve outcomes in men with advanced castration-resistant prostate cancer (CRPC).

Data from a phase 2 study presented at the American Society of Clinical Oncology Annual Meeting suggest that adding picoplatin to docetaxel and prednisone can improve disease control and progression-free survival (PFS).

Investigators found that picoplatin could be safely administered every three weeks for up to 10 cycles concurrently with full doses of docetaxel and prednisone, the current standard treatment for CRPC. The addition of picoplatin did not result in any new neurotoxicities.

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“The PSA response, disease control, and PFS in the this phase 2 trial are encouraging and suggest that picoplatin in combination with docetaxel and prednisone is active as first-line therapy for CRPC,” said William K. Oh, MD, Associate Professor of Medicine at Harvard Medical School and Clinical Director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute, both in Boston.

“There is no platinum-based chemotherapy approved for use in the treatment of prostate cancer.  I believe these results to date support the further development of picoplatin.”

Men with prostate cancer who no longer respond to hormonal therapies often have limited therapeutic choices. Picoplatin is a new-generation platinum-based chemotherapy agent designed to overcome platinum resistance associated with chemotherapy in solid tumors. Clinical studies suggest that picoplatin has an improved safety profile compared with other platinum-based chemotherapy agents.

The phase 2 trial evaluated the efficacy and safety of IV picoplatin (120 mg/m2) administered every three weeks in combination with full-dose docetaxel (75 mg/m2) and daily prednisone (5 mg) as a first-line treatment in 32 patients with metastatic CRPC who had not received prior chemotherapy.

The primary end point was PSA response, which was defined as a PSA reduction to at least 50% of baseline maintained for at least four weeks. Secondary end points included duration of PSA response, time to progression, radiologic response, survival, and safety.

Data showed that 78% of evaluable patients achieved a PSA response. Previous research has shown that CRPC patients who receive a two-drug regimen of docetaxel 75 mg/m2 and prednisone 5 mg achieve a PSA response of about 45%.

In this current study, the median PFS was 8.5 months. The radiologic responses showed that 58% of the evaluable patients achieved disease control (defined as a complete response, partial response, or stable disease). In 12 patients with measurable disease, the researchers identified one patient with a partial response and six with stable disease.

The main hematologic toxicity was neutropenia. Adverse events included alopecia (40% of patients), asthenia (27%), serum creatinine increase (23%), nausea (20%), and diarrhea (17%).

“This study showed that nearly 80% of the patients had a significant drop in their PSA,” said Dr. Oh, who noted that it is encouraging that the three-drug combination can shrink prostate cancers to the extent observed in the study.

“Chemotherapy, such as docetaxel, can depress platelets,” he said. “It doesn’t appear that adding [picoplatin] makes that side effect any worse.”

He added: “It is important for urologists to understand that options for castration-resistant prostate cancer are limited and that new treatments like picoplatin may enhance the ability of drugs like docetaxel to control prostate cancer.”