Gemcitabine plus epirubicin in patients with advanced urothelial carcinoma who are not eligible for platinum‐based regimens

Abstract

BACKGROUNDThe objective of this study was to evaluate the efficacy and toxicity of gemcitabine plus epirubicin in previously untreated patients with advanced urothelial carcinoma who were not eligible for cisplatin‐based regimens.METHODSPatients with advanced urothelial carcinoma and at least one of the following characteristics were eligible: impaired renal function (creatinine clearance < 60 mL per minute), an Eastern Cooperative Oncology Group performance status (PS) ≥ 2, and age ≥ 75 years. The treatment included epirubicin 70 mg/m2 as an intravenous bolus on Day 1 and gemcitabine 1000 mg/m2 over 30 minutes on Days 1 and 8 of a 21‐day cycle.RESULTSThirty‐eight patients entered the study, and a total of 152 cycles were administered, with a median of 4 cycles per patient (range, 1–6 cycles per patient). The following Grade 3–4 hematologic toxicities were reported (percent of cycles): neutropenia, 22.4%; anemia, 11.2%; and thrombocytopenia, 6.5%. No cardiac, renal, or hepatic toxicities were observed. Dose intensities of epirubicin and gemcitabine were 19.6 mg/m2 per week (84%) and 532.2 mg/m2 per week (80%), respectively. There were 2 complete responses (5.3%), 13 partial responses (34.2%), 11 patients with stable disease (28.9%), and 12 patients with progressive disease (31.6%), for an overall response rate of 39.5% (95% confidence interval, 25.1–55.1). The median progression free survival (PFS) and overall survival (OS) rates were 4.8 months and 8.0 months, respectively. The 1‐year survival rate was 38%, and the median PFS and OS were 6.4 months and 16.4 months, respectively, in patients with PS 0–1. Thirty patients were symptomatic: Seventeen patients (56.7%) achieved a complete response, and 5 patients (16.7%) achieved a partial symptomatic response.CONCLUSIONSAt the doses given in this study, gemcitabine and epirubicin had a good tolerability profile with interesting activity in patients with advanced urothelial carcinoma who were not fit for cisplatin‐based regimens. Cancer 2002;95:1444–50. © 2002 American Cancer Society.DOI 10.1002/cncr.10860

Schedule-Dependent Cytotoxic Interaction between Epidoxorubicin and Gemcitabine in Human Bladder Cancer Cells in Vitro

“…infusion of a combination of GEM and anthracycline derivatives in advanced breast (37), pancreatic (38 -40), bladder (41,42), and non-small cell lung cancers (43) could be further improved by using the most effective in vitro scheme. Moreover, the synergistic interaction observed after 1-and 24-h exposures to drugs opens up interesting perspectives for infusional or systemic clinical treatments, and the scheme defined as the most active in this preclinical study has provided the basis for the rationale in an ongoing intravesical Phase I-II clinical protocol.…”

Treatment of elderly patients with advanced urological cancer

“…Other combinations with paclitaxel, oxaliplatin or epirubicin have shown some effectivity in small phase II trials [39][40][41].…”

Biweekly Carboplatin/Gemcitabine in Patients with Advanced Urothelial Cancer Who Are Unfit for Cisplatin-Based Chemotherapy: Report of Efficacy, Quality of Life and Geriatric Assessment

“…We used PS >1, creatinine clearance <50 ml/min and comorbidities precluding cisplatin administration as the criteria for unfitness, similar to those used in a recent multicenter EORTC study [27]. Age has also been previously used by us and others as a criterion for unfitness [12, 28]. Nevertheless, we subsequently showed that elderly patients can tolerate cisplatin-based combination chemotherapy equally well as their younger counterparts, provided that no comorbidities are present and the other 2 criteria of fitness are fulfilled [6].…”

“…In one study including 38 patients, a combination of epirubicin and gemcitabine was used [28]. Age was used as an additional criterion for unfitness for cisplatin.…”