Rodolfo Passalacqua
, Maria Olga Giganti, Matteo Brighenti
, Bruno Perrucci, Maddalena Donini
, Federica Negri, Gianluca Tomasello, Laura Toppo
, Wanda Liguigli, Rossana Poli, Margherita Ratti, Luigi Benecchi, Andrea Prati
, Roberto Arnaudi
, Michele Potenzoni, Stefano Panni
, Silvia Lazzarelli
, 

Optimizing chemotherapy in patients with metastatic transitional-cell carcinoma: High rate of complete response with two sequential dose-dense regimens of cisplatin, gemcitabine, paclitaxel, followed by MVAC.

2015
J Journal of Clinical Oncology  303-303
 33 7_suppl
 10.1200/jco.2015.33.7_suppl.303

http://ascopubs.org/doi/abs/10.1200/jco.2015.33.7_suppl.303
 
Background: Currently, cisplatin, gemcitabine, paclitaxel (CGP) and MVAC are the most active regimens in transitional-cell carcinoma (TCC). We tested the hypothesis that two sequential non-cross-resistant, dose-dense (DD) regimens may target different cancer cells, avoid drug resistance, and improve response rate. Methods: This is a phase II, single institutional trial, including patients (pts) with bladder, renal pelvis, or ureteral TCC. Primary end point was the rate of complete response (CR) after two sequential DD regimens. Primary analysis was carried out in the intention to treat (ITT) population.Patients with histological diagnosis of TCC, PS 0–2 (ECOG), adequate organ function and no previous systemic regimens were treated with 4 cycles of CGP DD followed by 4 cycles of M-VAC DD. All received peg-filgrastim after chemotherapy. Pts were evaluated with CT scan at the baseline, after 4 cycles, at the end of chemotherapy and then every 3 months for 2 years and 6 months thereafter. Results: 44 consecutive pts followed in the same oncology institution were included. Males were 73%; median age was 66 years; median PS ECOG was 1; Bajorin risk factors was 0 in 36%, 1 in 48%, 2 in 16%. After the first 4 cycles of CGP DD, we observed 6.8% CR, 43.2% PR, 38.6% SD, and 11.4% PD. After the 4 sequential cycles of M-VAC DD, we observed a global 27.3% of CR, 15.9% of PR, 18.2% of SD, and 13.6% of PD. Median TTP was 9.66 months (95% CI, 6.7-13) and median OS was 18.6 months (95% CI, 12-30). Main grade 3–4 toxicity included asthenia (26%), anemia (26%), neutropenia (9.5%), febrile (7%), thrombocytopenia (12%), and neurological toxicity (5%). No toxic deaths were seen. After a median follow up of 50 months, 4 of 12 patients who obtained a complete response are free of disease since more than 3 years. Conclusions: This sequential use of these two DD regimens leads to a 4-fold increase in CR, an increase in survival, and a possible cure for some patients. A phase III trial is warranted.