Rate of durable complete remission (CR) using two sequential, dose-dense regimens of cisplatin, gemcitabine, paclitaxel (CGP) followed by m-VAC in patients with metastatic urothelial cancer (mUC).

Abstract

e15502 Background: mUC is a chemotherapy sensitive tumor. Currently, CGP and MVAC are the most active regimens in this setting. According to Norton and Simon hypothesis, the administration of two sequential non cross-resistant, dose-dense chemotherapy regimens may target different cancer cells, avoid drug resistance, improve response rate and CR. Methods: Patients with histological diagnosis of mUC, PS 0–2 (ECOG), adequate organ function and no previous systemic regimens were treated with 4 cycles of CGP dose-dense (Gemcitabine 1000 mg/m2 d 1, Paclitaxel 140 mg/m2 d 1, Cisplatin 70 mg/m2 d 2 plus PegFilgrastim 6 mg on day 3, every 2 weeks) followed by 4 cycles of M-VAC (Methotrexate 30 mg/m2 d 1,Vinblastine 3 mg/m2 d 2, Doxorubicin 30 mg/m2 d 2, Cisplatin 70 mg/m2 d 2 plus Pegfilgrastim 6 mg on day 3 every 2 weeks). All were evaluated with CT scan at the baseline, after 4 cycles, at the end of chemotherapy and then every 3 months for two years and 6 months thereafter. Metastatic sites included retroperitoneal nodes, lung, liver and bone. Results: From January 2007, 35 consecutive pts followed in the same oncology institution were included. Male were 74%; median age 65 years; median PS ECOG was 1; Bajorin risk factors was 0 in 37%, 1 in 43%, 2 in 20%. All pts were hospitalized for three days and received chemotherapy with hydration and supportive therapy. After the first 4 cycles of CGP we observed 14.3% CR, 48.6% PR, 22.9% SD and 14.3% PD. After the 4 sequential cycles of M-VAC we observed a global 37.1% of CR, 25.7% of PR, 8.6% of SD and 28.6% of PD. Median TTP was 9.9 months ( 95 % CI, 7.53-14.83) and median OS was 24.27 months ( 95 % CI, 10.03-38.43). Main grade 3–4 toxicity included asthenia ( 27%), anemia (21%), neutropenia (12 %), febrile (9%), thrombocytopenia (9%) and peripheral neuropathy (6 %). After a median follow up of 33 months, 6 of 13 patients who obtained a complete response are free of disease. Conclusions: These data confirm that the sequential use of this two dose-dense regimens is very active and 17 % of patients maintained a CR status.