Triple therapy may be option in hormone-refractory prostate cancer

August 1, 2006

Atlanta-Patients with metastatic hormone-refractory prostate cancer who were treated with triple therapy using docetaxel (Taxotere), thalidomide (Thalomid), and estramustine phosphate sodium (Emcyt) demonstrated a 90% response rate, defined as a decline in PSA levels of at least 50%, reported researchers from the National Cancer Institute, Bethesda, MD.

Atlanta-Patients with metastatic hormone-refractory prostate cancer who were treated with triple therapy using docetaxel (Taxotere), thalidomide (Thalomid), and estramustine phosphate sodium (Emcyt) demonstrated a 90% response rate, defined as a decline in PSA levels of at least 50%, reported researchers from the National Cancer Institute, Bethesda, MD.

Of 20 patients originally enrolled on the study, however, only three continue to receive therapy. Thirteen patients withdrew because of disease progression, and four chose to discontinue due to toxicity or other reasons, the NCI researchers reported at the AUA annual meeting here.

"Initial results are encouraging, with 90% PSA response. We don't have survival data yet, but patients generally tolerated the regimen well," said Shenhong Wu, MD, clinical fellow in NCI's Medical Oncology Branch, who worked on the study with William Dahut, MD, and colleagues.

The overall objective of the study was to determine the impact of combining docetaxel, thalidomide, and estramustine on PSA levels to determine whether the combination warrants further investigation for the treatment of hormone-refractory disease.

Twenty chemotherapy-naïve patients with progressive metastatic hormone-refractory prostate cancer were enrolled in this single arm, open-label, phase II trial. Baseline characteristics included a median age of 70 years (range, 52 to 77 years), Gleason score of 8 (range, 6 to 10), and median PSA of 138.6 microgams/L (range, 1.4 to 486 microgams/L).

Patients were treated until disease progression or intolerable toxicity, or until they asked to discontinue treatment. PSA was measured every 4 weeks, and computed tomography (CT)/bone scans were performed 2 months after the start of the trial and every 3 months thereafter.

All 20 patients received at least two cycles of treatment. The mean number of cycles received was 7.8 (range, two to 20 cycles). Of 10 patients with measurable soft tissue disease, two (20%) demonstrated a partial response to therapy and eight (80%) had stable disease.

Grade 3/4 toxicities included four incidents of lymphopenia, three incidents of hypophasphatemia, two incidents each of infusion reaction and aspartate aminotransferase/alanine aminotransferase elevation, and one incident each of deep venous thrombosis, fatigue, pulmonary embolism, sensory neuropathy, and hyponatremia.

The most common grade 1/2 toxicities were 12 incidents of sensory neuropathy, 10 each of leg edema and taste alteration, nine each of diarrhea and constipation, and eight each of dizziness and nausea/vomiting.

"The limitation of this study is its small size," Dr. Wu acknowledged.

Second triple Tx trial underway

"Currently, we are testing a docetaxel, bevacizumab (Avastin), and thalidomide combination. Initial results [also show a] 90% PSA response. Patients tolerate treatment very well," he added. "We are expanding that [phase II] study."