Clinical report 1207 Gemcitabine plus docetaxel as first-line biweekly therapy in locally advanced and/or metastatic urothelial carcinoma: a phase II study Bruno Neri a , Laura Vannini, Clara Giordano a , Raffaella Grifoni a , Pietro Pantaleo, Valentina Baldazzi b , Alfonso Crisci a,b , Alberto Lapini b , Andrea Raugei b and Marco Carini b The purpose of the study was to evaluate objective response rate, survival and toxicity of the combination of gemcitabine–docetaxel administered on a biweekly schedule as first-line treatment in advanced/relapsed or metastatic urothelial carcinoma. Treatment consisted of the sequenced administration of gemcitabine 1500 mg/m 2 and docetaxel 60 mg/m 2 (2 h intravenous infusion) on days 1, 14 of a 28-day cycle for 6 months. A total of 33 patients, 22 men and 11 women, were enrolled, aged 41–75 years (median 64 years). The majority of patients had a good performance status (94%; status < 2). Thirteen patients had locally advanced disease (39%) and 20 metastasic disease (41%). A total of 178 treatment cycles were administered with a median number of 5.4 cycles for a patients (range 2–8). Toxicity was primarily hematologic with the most frequent grade > 2 being neutropenia (11%), with three episodes of febrile neutropenia. Anemia and thrombocytopenia were milder and had a lower incidence. The most frequent nonhematological toxicities were alopecia, followed by asthenia. Cardiac and pulmonary toxicity was minimal. No toxic deaths were recorded during study and follow-up. Overall response rate was 53.1%, including four complete responses (12.5%) and 13 partial responses (40.6%), whereas six patients (18.8%) had disease stabilization. Median time to progression was 10.2 months (95% confidence interval: 5.1–13.7), with a median survival of 14.8 months (95% confidence interval: 9.4–20.2) after an observation of 30 months (range 4–30 + ). The results of this study suggested that combination therapy with gemcitabine and docetaxel administered twice a week is particularly active and well tolerated as first-line treatment in advanced and/or metastatic urothelial carcinoma. Once data are confirmed in a larger study and longer follow-up, the favorable toxicity profile of this regimen may offer an interesting alternative to the cisplatin-based regimen. Anti-Cancer Drugs 18:1207–1211  c 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins. Anti-Cancer Drugs 2007, 18:1207–1211 Keywords: chemotherapy, docetaxel, gemcitabine, urothelial carcinoma a Department of Oncology, Centre of Experimental and Clinical Oncology and b Department of Urology, University of Florence, Italy Correspondence to Professor Bruno Neri, MD, Department of Oncology, Centre of Experimental and Clinical Oncology, University of Florence, Azienda Ospedaliero Universitaria, Careggi, Viale Pieraccini 17, 50139 Florence, Italy Tel: +39 055 7949748; fax: +39 055 7948237; e-mail: bruno.neri@unifi.it Received 30 March 2007 Revised form accepted 5 June 2007 Introduction Urothelial carcinoma (UC) is the fourth most frequent malignancy in Europe, accounting for about 7% of all human neoplasms. About new 136 000 cases are recorded each year with an incidence of 32 instances out of every 100 000 men and nine out of 100 000 women. Overall, about 49 000 deaths in Europe are related to this neoplasm [1]. To date, a cure is not possible for the majority of patients with locally advanced/recurrent or metastatic disease. The standard therapy for patients affected by invasive cancer of the bladder is radical cystectomy preceded or followed by chemotherapy. As with surgery alone the survival rate is particularly low, systemic chemotherapy appears to be the only treatment potentially capable of lengthening survival. In the past 10 years, the most widely employed regimens in advanced and/or metastatic UC have been cisplatin-based combi- nations like cisplatin–methotrexate–vinblastine or me- thotrexate–vinblastine–adriamicina–cisplatin (M-VAC) [2], which offer a high rate of objective responses (40–70%) although at the expense of major toxicities, mainly myelosuppression, nausea, vomiting and nephrotoxicity [3]. Furthermore, only 5% of patients achieve a survival of more than 5 years [4–6]. More recently, a phase III study has demonstrated that the combination gemcitabine– cisplatin could achieve the standard of care of M-VAC, but with a significantly lower toxicity [7]. This result is particularly significant if we consider that symptom palliation is one of the major goals in advanced UC. In the meantime, oncological research has focused on newer agents and combinations potentially capable of increasing response rates and survival time with acceptable toxicity grades. Over the past several years clinical studies have shown that taxanes (paclitaxel–docetaxel) are among the 0959-4973  c 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins