[Show abstract][Hide abstract] ABSTRACT: Chemotherapy with gemcitabine and cisplatin (GC) is an active regimen in advanced transitional cell carcinoma (TCC). Traditionally, GC has been administered as a 4-week schedule. However, an alternative 3-week schedule may be more feasible. Long-term survival data for the alternative 3-week schedule and comparisons of the feasibility and toxicity between the two schedules have not previously been published.
We performed a retrospective analysis of patients with stage IV TCC, treated with GC by a standard 4-week or by an alternative 3-week schedule.
A total of 212 patients received GC (3-week; n = 151, 4-week; n = 61). We found no statistical differences in overall survival between the two schedules (hazard ratio 1.15, 95% CI 0.83-1.59), p = 0.40). Five-year survival rates were 14.9% and 11.8% for the 3- and 4-week schedule, respectively (p = 0.94). Response rates were 59.7% and 55.6%, respectively (p = 0.61). Toxicity was less pronounced in the 3-week schedule with regards to neutropenia, thrombocytopenia, and transfusion rates. Hematologic toxicity at day 15 in the 4-week schedule was common, leading to dose omissions in 47% of cycles. Dose intensity for gemcitabine was accordingly lower in the 4 week-schedule. The higher dose intensity of cisplatin in the 3-week schedule, did not lead to increased renal toxicity. In 13 patients with impaired renal function, cisplatin was split into 2 days, which was feasible and efficient.
Efficacy parameters for the GC 3-week schedule were comparable to those for the 4-week schedule, whereas toxicity was less pronounced. The 3-week schedule may be an effective and feasible alternative GC-schedule.
[Show abstract][Hide abstract] ABSTRACT: The objective was to evaluate response and survival, as well as efficacy of subsequent supplementary treatment and follow-up strategy in patients with locally advanced transitional cell carcinoma of the bladder following combination chemotherapy with gemcitabine and cisplatin (GC).
A total of 84 patients with locally advanced (T4b, Nx, M0 or Tx, N2-3, M0) received GC. After chemotherapy, the strategy was close surveillance in patients with complete response, and supplementary radical cystectomy or radiotherapy whenever possible in patients with partial response.
A total of 25 patients (29.8%) with complete response to chemotherapy were followed by close surveillance. This group achieved a median overall survival of 47.6 mo. Another 25 patients had partial response to chemotherapy. Of these patients, 16 had supplementary treatment, with 10 achieving "no evidence of disease" (NED). Thus, a total of 35 patients achieved NED with a median overall survival of 48.7 mo versus 10.2 mo in patients not achieving NED (hazard ratio=0.10; 95%CI, 0.05-0.20; p<0.0001). The rate of NED was higher in the group of patients who had a cystectomy compared with the group who received radiotherapy as supplementary treatment.
In patients with locally advanced bladder cancer, NED following chemotherapy alone or chemotherapy plus supplementary cystectomy or radiotherapy is essential to achieve long-term survival. Patients with a partial response should be offered radical cystectomy whenever possible, which seems to be superior to radiotherapy. Close surveillance may be an alternative to immediate cystectomy in patients with complete response following chemotherapy.
European Urology 09/2007; 52(2):478-86. · 10.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cisplatin-containing chemotherapy is the standard of care for patients with locally advanced and metastatic transitional cell carcinoma of the urothelium. The response rate is approximately 50% and tumor-derived molecular prognostic markers are desirable for improved estimation of response and survival.
Affymetrix GeneChip expression profiling was carried out using tumor material from 30 patients. A set of genes with an expression highly correlated to survival time after chemotherapy was identified. Two genes were selected for validation by immunohistochemistry in an independent material of 124 patients receiving cisplatin-containing therapy.
Fifty-five differentially expressed genes correlated significantly to survival time. Two of the protein products (emmprin and survivin) were validated using immunohistochemistry. Multivariate analysis identified emmprin expression (hazard ratio, 2.23; P < 0.0001) and survivin expression (hazard ratio, 2.46; P < 0.0001) as independent prognostic markers for poor outcome, together with the presence of visceral metastases (hazard ratio, 2.62; P < 0.0001). In the clinical good prognostic group of patients without visceral metastases, both markers showed significant discriminating power as supplemental risk factors (P < 0.0001). Within this group of patients, the subgroups of patients with no positive, one positive, or two positive immunohistochemistry scores (emmprin and survivin) had estimated 5-year survival rates of 44.0%, 21.1%, and 0%, respectively. Response to chemotherapy could also be predicted with an odds ratio of 4.41 (95% confidence interval, 1.91-10.1) and 2.48 (95% confidence interval, 1.1-5.5) for emmprin and survivin, respectively.
Emmprin and survivin proteins were identified as strong independent prognostic factors for response and survival after cisplatin-containing chemotherapy in patients with advanced bladder cancer.
Clinical Cancer Research 08/2007; 13(15 Pt 1):4407-14. · 7.84 Impact Factor