Weekly Administration of Docetaxel and Epirubicin as First-Line Treatment for Hormone-Refractory Prostate Carcinoma

Abstract

Androgen-independent prostate carcinoma (AICP) is one of the tumors that continue to respond poorly to chemotherapy. Recently, protocols based on the use of docetaxel have significantly improved survival for patients in this disease. In other types of neoplastic disease, combined therapy with taxanes and anthracycline derivatives has been shown to produce additive effects in terms of growth inhibition, and superior tolerability when associated with weekly administration schedules. These findings prompted us to examine the tolerability and efficacy of weekly treatment of AICP with docetaxel (DOX) plus epirubicin (EPI). We enrolled 35 chemotherapy-naive men with AICP (mean age 72 years, range 68-77) and normal hepatic, renal, and cardiac function. The chemotherapy protocol provided for the IV administration of DOX (30 mg/m2) and EPI (30 mg/m2) on days 1, 8, and 15 every 28 days. Treatment was continued for 6 months or until disease progression and/or unacceptable toxicity was observed. Serum levels of prostate-specific antigen (PSA) were monitored in all patients, and reductions from baseline values of >50% were considered indicative of positive responses to treatment. Thirty-four patients were included in the analysis of toxicity, and objective responses to treatment were assessed in the 28 patients with measurable lesions. Nineteen patients (56%) experienced PSA reductions of >50% that persisted for more than 4 weeks. The response to therapy was classified as complete in 1 of the 28 patients (4%) with measurable disease (at the lymph node level). Thirteen others (13/28, 46%) had partial responses, in nine (32%) the disease remained unchanged, and progression was observed in the remaining five (18%); overall response rate was 50% (CR + PR). Of the 27 patients with pain at the time of enrollment, 16 (59%) experienced pain reduction during treatment. The median time to disease progression was 11.7 months (95% CI: 7.7-15.7) while the median survival time was 18.7 months (95% CI: 12.3-25.1). During the study, four patients developed grade 3 anemia and leukopenia, which was reversible in all cases. Lower grades of asthenia, nausea, vomiting, diarrhea, and peripheral edema were also observed. There were no cases of cardiotoxic effects. Alopecia was frequent but reversible in all cases. The results of this preliminary study indicate that the combined administration of DOX and EPI for treatment of AIPC is effective and well tolerated. The weekly administration of the drug combination appears to be a promising approach to the treatment of these tumors.

Docetaxel and Doxorubicin Codelivery by Nanocarriers for Synergistic Treatment of Prostate Cancer

“…Combination of DOC with other drugs has been developed for the treatment of PCA (Scheme 1). Studies have indicated that anthracyclines can enhance the inhibitory effect of DOC against PCA (Pienta, 2001;Kouroussis et al, 2005;Mackler and Pienta, 2005;Neri et al, 2005;Petrioli et al, 2007;Neri et al, 2009). Several studies have verified that the combination of DOC with DOX has a synergistic effect in the treatment of PCA.…”

“…DOC remains the mainstream therapeutic agent for PCA treatment and is combined with other drugs, including mitoxantrone and estramustine, to treat PCA (Sinibaldi et al, 2002;Petrylak et al, 2004). Several clinical studies have demonstrated that DOC combined with anthracyclines could increase the anti-PCA effect because anthracyclines would enhance the sensitivity of the PCA cells to DOC (Pienta, 2001; Kouroussis et al, 2005;Mackler and Pienta, 2005;Neri et al, 2005;Petrioli et al, 2007;Neri et al, 2009). DOX is a kind of anthracycline that can prevent DNA remodeling (Pommier et al, 2010).…”

Anticancer Activity of Acanthopanax trifoliatus (L) Merr Extracts is Associated with Inhibition of NF-κB Activity and Decreased Erk1/2 and Akt Phosphorylation

“…Early stage prostate cancer requires androgen for growth and thus responds well to androgen deprivation therapy (Loblaw et al, 2007), but tumors become resistant to this therapy as disease progresses (Pilat et al, 1998;So et al, 2005;Schroder, 2008;Chi et al, 2009). Chemotherapy is the primary treatment option for late-stage prostate cancer patients, but this has limited efficacy and serious toxic side effects and the prognosis for these patients is very poor (Gomella et al, 2009;Neri et al, 2009). Therefore, there is a need for novel therapeutic approaches for treating and preventing androgen-independent prostate cancer while minimizing toxic side effects.…”