Triple-Drug Regimen Disappointing In Hormone-Refractory Prostate Cancer

NEW YORK (Reuters Health) - In men with hormone-refractory prostate carcinoma (HRPC), weekly paclitaxel, estramustine phosphate, and etoposide is not superior to less toxic two-drug taxane/estramustine phosphate combinations

The findings are from a phase II trial, published in the November 15th issue of the journal Cancer. Lead investigator Dr. Anthony A. Meluch of the Sarah Cannon Cancer Center in Nashville, Tennessee, and colleagues conclude that "further development of this three-drug regimen is not recommended."

In an earlier study, the combination of paclitaxel (administered every 3 weeks), oral estramustine phosphate, and oral etoposide, was highly active against HRPC, but also highly toxic.

In the current study, Dr. Meluch's team tried to maintain efficacy and reduce toxicity of this three-pronged approach by administering paclitaxel weekly instead of every 3 weeks, in combination with the other two agents. "Weekly paclitaxel (70-100 mg/m² per week) has proven effective in a variety of tumors with reduced hematologic toxicity, neuropathy, and arthralgias," they note.

They treated 42 HRPC patients with paclitaxel (50 mg/m²) as a 1-hour IV infusion on days 1, 8, and 15; oral estramustine (280 mg tid) and oral etoposide (50 mg bid) for 14 days of a 28-day cycle.

Excessive myelosuppression seen in the first three patients led them to subsequently decrease the duration of estramustine and etoposide from 14 days to 10 days in each course.

Despite the hope that the weekly paclitaxel would be less toxic, roughly half of the patients experienced Grade 3 or 4 neutropenia, more than one quarter were hospitalized for neutropenic fever, one third had severe fatigue, and two patients died of sepsis related to treatment.

Although the three-drug regimen was active, "the results did not appear any better than the results achieved with less toxic [regimens]," the team reports.

Several "promising" approaches to HRPC that offer the "dual hope of maximizing efficacy with minimal toxicity to normal tissues" are on the horizon, Dr. Samira Syed of the University of Texas Health Science Center in San Antonio notes in a related editorial. These include epidermal growth factor receptor inhibitors, antiangiogenesis agents, and monoclonal antibodies targeting prostate specific membrane antigen.

Source: Cancer 2003;98:2088-2090,2192-2198. [ Google search on this article ]

MeSH Headings: Antineoplastic Agents, Combined : Clinical Trials : Drug Toxicity : Environment and Public Health : Epidemiologic Methods : Evaluation Studies : Health : Health Occupations : Health Services Administration : Medicine : Investigative Techniques : Outcome and Process Assessment (Health Care) : Population Characteristics : Preventive Medicine : Public Health : Quality of Health Care : Specialties, Medical : Epidemiologic Study Characteristics : Treatment Outcome : Outcome Assessment (Health Care) : Clinical Trials, Phase II : Health Care Quality, Access, and Evaluation : Health Care Evaluation Mechanisms : Analytical, Diagnostic and Therapeutic Techniques and Equipment : Biological Sciences : Health Care

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