Chemo combination increases overall survival in PCa patients

November 1, 2007

In patients with castration-refractory prostate cancer, the addition of estramustine (Emcyt) to chemotherapy increases time to PSA progression and overall survival compared with chemotherapy alone, according to a meta-analysis published in The Lancet Oncology (2007; 8:994-1000). However, this benefit should be balanced with the risk of increased thromboembolic events in patients who receive the combination therapy compared with chemotherapy alone.

In patients with castration-refractory prostate cancer, the addition of estramustine (Emcyt) to chemotherapy increases time to PSA progression and overall survival compared with chemotherapy alone, according to a meta-analysis published in The Lancet Oncology (2007; 8:994-1000). However, this benefit should be balanced with the risk of increased thromboembolic events in patients who receive the combination therapy compared with chemotherapy alone.

Researchers from the Institut Gustave Roussy, Villejuif, France, and others systematically searched for randomized clinical trials that compared chemotherapy regimens with and without estramustine in patients with histologically proven prostate cancer, and were published between 1966 and 2004. Data from these studies were verified centrally, and updated individual patient data were analyzed. The primary endpoint was overall survival. Secondary endpoints were PSA response, time to PSA progression, and toxicity.

The search identified 605 patients who had been randomly assigned to chemotherapy plus estramustine or to chemotherapy alone. Median follow-up was 2.8 years, and 510 deaths had occurred by the end of follow-up.

Cox regression analysis stratified by trial showed that concentrations of serum hemoglobin (p<.0001), use of chemotherapy plus estramustine (p=.008), performance status (p=.002), and serum PSA concentrations (p=.04) were associated independently with overall survival. Overall survival was significantly better in patients assigned chemotherapy plus estramustine (p=.008). Estimated absolute increase in overall survival when estramustine was added to chemotherapy was 9.5% at 1 year after randomization.

"We did not note a significant association between treatment effect on overall survival and age, concentration of serum hemoglobin, performance status, or serum PSA concentration," the authors wrote.

Patients assigned chemotherapy and estramustine suffered more grade 3 or grade 4 thromboembolic events  than did with those receiving chemotherapy alone (12 of 271 vs. 1 of 275).