Weekly paclitaxel and epirubicin in the treatment of symptomatic hormone-refractory advanced prostate carcinoma: report of a phase II trial

Abstract

The efficacy of weekly paclitaxel in androgen-independent prostate cancer and its addictive cytotoxicity with anthracycline derivatives led us to determine the safety and efficacy of a weekly schedule of paclitaxel and epirubicin. Between October 2000 and November 2002, 32 patients were enrolled in this study. Patients characteristics included a median age of 72 years (range 68-77), adequate hepatic, cardiac, renal and bone marrow functions, ECOG performance status of 1-2, and no prior chemotherapy. All patients had received hormonal manipulation and seven patients (22%) had received prior palliative radiation therapy. The regimen consisted of paclitaxel 70 mg/m2 i.v. infusion for 2 h and epirubicin 30 mg/m2 in bolus every week. Treatment was continued for 3 months or until disease progression or unacceptable toxicity were observed. During the study, prostate-specific antigen (PSA) was monitored and response was defined as a 50% reduction in PSA levels, to be confirmed 4 weeks later. Thirty-one patients were evaluable for toxicity and 21 for objective response. Seventeen patients (57%) had a decline above 50% in PSA level that lasted more than 4 weeks with a median time to PSA progression and a median duration of PSA response of approximately 5.5 months. Ten of the 21 patients with measurable disease (47%) had a confirmed objective response (one complete response and 20 partial responses). Thirteen of 25 symptomatic patients (56 %) had improvement in pain. The median time to disease progression was 7.6 months and the median survival was 12.9. The most prominent grade 3 toxicities were reversible myelosuppression and fatigue. Nausea, vomiting, diarrhea and peripheral edema were minimal. No evidence of cardiac toxicity was recorded. Alopecia was frequent, but reversible, in all patients. We conclude that despite the small sample size, this study demonstrates that the combination of weekly paclitaxel and epirubicin is a well-tolerated regimen for androgen-independent prostate cancer. The results imply that a combination of these agents in a weekly schedule may have clinical potential in prostate cancer treatment.

Effective chemotherapy for hormone-refractory prostate cancer (HRPC): Present status and perspectives with taxane-based treatments

“…Of 16 published phase II studies, Paclitaxel was combined with Carboplatin, Estramustine, Etoposide, and Epirubicin [46,[47][48][49][50][51][52][53][54][55][56][57][58][59][60]. There are synergistic in vitro data of the combination of Paclitaxel and Gemcitabine [61].…”

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).…”

Phase II study of mitoxantrone and ketoconazole for hormone‐refractory prostate cancer

“…Therefore, although the combination of mitoxantrone plus ketoconazole needs to be studied further, existing data support the notion that there is an added benefit to combining these 2 agents. It also should be noted that epirubicin has an activity spectrum similar to that of doxorubicin and can be well tolerated and active in hormone-refractory prostate cancer, 35,36 and therefore also may be suitable in combination with ketoconazole.…”