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Emcyt/Taxol Studied in Refractory Prostate Ca

Emcyt/Taxol Studied in Refractory Prostate Ca

PHILADELPHIA--Ongoing trials of a protocol that provides prolonged
exposure to estramustine phosphate (Emcyt) and 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,
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.

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