الفهرس 
Bladder cancerOnly 14 pages are availabe for public view
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Abstract
Bladder cancer is the most common malignant tumor in Egyptians accounting for 20-30% of all malignant tumors presenting to NCI. Systemic chemotherapy is the only modality that has been shown in phase III trials to improve survival in responding patients with advanced bladder cancer. The gemcitabine-cisplatin combination has proven to be well tolerated and active with overall response rates ranging from 11% to 57%. This study aims to evaluate overall response and toxicity of both standard & prolonged infusion gemcitabine-cisplatin regimens in advanced bladder cancer patients and at same time to evaluate the prognostic and predictive values of some molecular markers in advanced bladder cancer patients (p53 and Ki-67). Over the period from May 2007 to May 2010, sixty patients of inoperable, metastatic, or recurrent bladder cancer were randomized to either prolonged (arm 1) or short (arm 2) infusion gemcitabine and cisplatin. The clinical features of the 60 patients included in this study were as follow: Forty-five patients (75%) were males and 15 patients (25%) were females with a ratio of 3:1. The median age of the whole group was 60 years (range: 40-73 years). Forty-three patients (72%) had transitional cell carcinoma, 16 patients (27%) had squamous cell carcinoma, and 1 patient (1%) had undifferentiated carcinoma. Grade I and II tumors were presented in 32 patients (53.3%) while grade III tumors were present in 28 patients (46.7%). Forty-eight patients (80%) had inoperable bladder cancer, 33 of them had metastases in addition (lymph nodes 11, liver 7, bone 6, lung 4 and multiple sites 5). Six patients were treated from metastases that have developed after surgical removal of primary bladder cancer, 4 patients were treated from local recurrence only and 2 patients were treated from local recurrence and metastases. Among the 60 patients randomized in this study, 52 patients were evaluable (26 patients in arm 1 and 26 in arm 2). Complete response (CR) rate was achieved in 15.3% (4/26 patients) of arm 1 and 7.6% (2/26 patients) of arm 2 that was proved radiologically and pathologically. Eight patients in arm 1 (30.7%) and 9 patients (34.6%) in arm 2 had partial response on therapy. Thus the overall response rate of patients in arm 1 and arm 2 was 46% (12/26 patients) and 42% (11/26 patients) respectively. Stable disease was observed in 4 patients in arm 1 (15.3%) and 5 patients in arm 2 (19%). Progressive disease was observed in 10 patients in arm 1 (38.4%) and 10 patients in arm 2 (38.4%). For arm 1 patients, the median overall survival time was 8.5 months (range 1-17months) with one -year survival rate of 25% while for arm 2 the median survival time was 8 months (range 1-13months) and one- year survival rate was 7% (p value = 0.4). The median time to disease progression was 6.5 months and 6 months in arm 1 and arm 2 respectively. The toxicity pattern was generally tolerable. No treatment-related deaths occurred among the 60 patients. Both hematological and Non-hematological toxicity were similar in both arms; with no statistically significant differences. This study demonstrated that cisplatin and low-dose prolonged infusion gemcitabine regimen was not inferior to cisplatin and high- dose short infusion gemcitabine regimen in terms of overall survival, time to disease progression, response rates and favorable toxicity profile. Conclusion: In the treatment of advanced bladder cancer, gemcitabine in low dose and prolonged infusion in combination with cisplatin has low toxicity and has activity comparable with gemcitabine in higher dose in standard brief infusion. The good efficacy, remarkably mild hematologic toxicity and lower drug costs of low-dose gemcitabine and prolonged infusion, make it appears as an attractive option for Egyptian patients with advanced bladder cancer particularly for the elderly or those without good economic condition as, a great proportion of patients discontinue their treatment because of failing to afford drug costs rather than intolerable toxicities. Therefore, lowering costs for gemcitabine without lowering its activity is definitely meaningful.