PHILADELPHIA--Ongoing trials of a protocol that provides prolonged exposure to estramustine(Drug information on estramustine) phosphate (Emcyt) and paclitaxel(Drug information on paclitaxel) (Taxol) have produced promising results in men with hormone-refractory prostate cancer, Gary Hudes, MD, told Oncology News International.
"The number and quality of responses have impressed us. This combination looks to be more active than Emcyt and vinblastine(Drug information on vinblastine), although obviously it is going to take more experience to better estimate the activity," said Dr. Hudes, associate member, Department of Medicine, Fox Chase Cancer Center.
Favorable results from a phase II study of estramustine/vinblastine at Fox Chase led Dr. Hudes' group "back to the laboratory" to look at estramustine and paclitaxel. "The rationale for the two combinations was similar--combining drugs that have complementary targets and different clinical toxicities," he said in his presentation of the research at the Chemotherapy Foundation Symposium XII, sponsored by Mount Sinai School of Medicine.
In these lab studies, prolonged exposure to estramustine/paclitaxel produced synergistic cytotoxic effects against D-145 androgen-independent cell lines that were both estramustine sensitive and estramustine resistant. For the phase I study at Fox Chase Cancer Center, a 96-hour infusion schedule of paclitaxel and continuous oral daily administration of estramustine were used to mimic the preclinical model.
In the phase I trial, estramustine did not alter paclitaxel clearance or distribution during the first cycle of treatment, and paclitaxel plasma levels were similar to those seen with single-agent use. "This had been a concern because Taxol metabolism and clearance depend on hepatic metabolism, and estramustine can affect hepatic enzymes," Dr. Hudes said.
The regimen for both the phase I and II studies is paclitaxel, 120 mg/m² by 96-hour infusion every 3 weeks, and estramustine phosphate, 600 mg/m²/day orally in two or three divided doses between meals, starting 1 day before the paclitaxel infusion and continuing throughout the protocol treatments. Patients receive a standard premedication regimen to prevent hypersensitivity reactions.
Dr. Hudes reported that of the 17 patients in the phase I study, four had hormone-refractory prostate cancer. Seven have received at least one cycle of treatment on the phase II study, and six patients who were not eligible for either study for a variety of reasons have also been treated. The median age was 66, and most patients were symptomatic.