Gemcitabine-cisplatin versus methotrexate, vinblastine, doxorubicin and cisplatin in locally advanced or metastatic transitional cell carcinoma of the bladder

To compare the efficacy and toxicity of the combination of gemcitabine plus cisplatin [GC] and methotrexate, vinblastine, doxorubicin plus cisplatin [MVAC] in the treatment of patients with locally advanced or metastatic transitional cell carcinoma [TCC] of the bladder. Forty five patients with locally advanced or metastatic TCC of the bladder were r and omized to GC [gemcitabine 1000mg/m[2] days 1, 8 and 15; cisplatin 70mg/m[2] day 2] or st and ard MVAC [methotrexate 30mg/m[2] days 1, 15 and 22; vinblastine 3mg/m2 on days 2, 15 and 22; doxorubicin 30mg/m[2] on day 2; and cisplatin 70mg/m[2] on day 2]. The cycles were repeated every 28 days for a maximum of six cycles. Forty five patients were r and omized [GC, n=23; MVAC, n=22]. Overall response rates were similar on both. arms [GC, 47.8%; MVAC, 45.5%, p=0.934]. Overall survival and progression free-survival were similar on both arms [HR, 1.067; 95% CI, 0.595 to 1.915, p=0.828, and HR, 0.861; 95% Cl, 0.461 to 1.610, p=0.640, respectively]. Patients on the [GC arm received a median of six cycles compared with a median of 4 cycles for patients on the MVAC arm. Dose adjustments occurred in only 40% of the cycles with GC and in 64.7% with MVAC. Grades 3 and 4 anemia and thrombocytopenia were seen more often on GC arm than on MVAC arm [26% vs 18.1%, p=0.776 and 43.5% vs 22.7%, p=0.265 respectively]. However, the RBC and platelet transfusion rates were similar on both arms. More MVAC treated-patients compared with GC treated-patients had grade 3 and 4neutropenia [81.8% vs 60.8% respectively, p=0.043], neutropenic fever [18.2% vs 0% respectively p=0.049], neutropenic sepsis [13.6% vs 0% respectively, p=0.089], grade 3 and 4 mucositis [27.2% vs 0% respectively, p=0.027] and alopecia [54.5% vs 8.7% respectively, p=0.001]. More patients on GC had better results than MVAC patients as regard weight and performance status. Combination chemotherapy of gemcitabine plus cisplatin provides similar outcomes to that of st and ard MVAC in treatment of patients with locally advanced or metastatic TCC of the bladder with a better safety profile and tolerability

Activity and safety of navelbine and fractionated dose doxorubicin as first line therapy for advanced breast cancer

Very promising results have been obtained by vinorelbine-doxorubicin combination in the treatment of advanced breast cancer. However previous experience with schedules in which the doxorubicin dose was administered on day 1 alone were associated with a high level of cardiac toxicity. There is evidence that fractionating the dose of doxorubicin and administering it at weekly intervals may reduce the cardiac toxicity without substantially impairing the efficacy. To asses the efficacy and tolerability of vinorelbine and fractionated dose doxorubicin [the total dose was divided into two administrations on days 1 and 8] in patients with advanced breast cancer. Fifty-two patients with locally advanced or metastatic breast cancer who had received no prior chemotherapy except in an adjuvant setting were entered into the study. They were treated vinorelbine 25 mg/m[2] plus doxorubicin 25 mg/m[2] both administered in day 1 and 8 every three weeks. Objective responses were observed in 30 patients [71, 4%]. There were 7 [16.6%] complete responses [CR] and 23 [54.8%] partial responses [PR]. In addition 10 patients [23.8%] had stable disease [SD] and 2 [4.8%] progressed while on treatment. Twenty of 28 patients with visceral disease responded to treatment [71.4%]. The median duration of response was 11.5 months [range, 2 to > 24+] and the median overall survival was 21.5 months [range 2 to > 36+]. Hematological toxicity was predominantly related to neutropenia with Grade 3-4 reported in 18.1% of the cycles. Alopecia was reported in 66.7% of the patients. Grade 3 nausea/vomiting in 3.6% of the cycles. No clinically significant cases of cardiac dysfunction were seen. The fractionated schedule of vinorelbine and doxorubicin is associated with excellent tolerability [especially cardiac], coupled with high levels of activity comparable to those observed using the un-fractionated regimen