Chemotherapy for Muscle-invasive Bladder Cancer: Impact of Cisplatin Delivery on Renal Function and Local Control Rate in the Randomized Phase III VESPER (GETUG-AFU V05) Trial.
BACKGROUND
Cisplatin-based combination chemotherapy before surgery is the standard of care for muscle-invasive bladder cancer. However, the optimal chemotherapy modalities have not been precisely defined to date.


PATIENTS AND METHODS
In the VESPER trial, patients received after randomization either gemcitabine and cisplatin (GC, 4 cycles) or methotrexate, vinblastine, doxorubicin and cisplatin (dose dense [dd]-MVAC, 6 cycles). Creatinine clearance (CrCl) was calculated before each cycle according to the Cockroft and Gault formula. Definition criteria for local control after neoadjuvant chemotherapy included pathological complete response (ypT0N0), pathological downstaging (<ypT2N0) and organ-confined disease (<ypT3N0) at cystectomy. Baseline and treatment characteristics were studied in multivariate logistic models to determine their potential role for each type of pathological responses.


RESULTS
A total of 2128 cycles of chemotherapy were delivered, including 2120 (99.6%) with cisplatin. Full doses of cisplatin were given in 1866 (88%) cycles. Twenty-three (4.7%) patients had to stop chemotherapy (12 GC, 11 dd-MVAC) because of renal failure. No difference in CrCl median values was observed between the 2 regimens during the first 4 cycles. A mild decrease occurred thereafter in patients treated with 2 additional cycles of dd-MVAC. A minimum total dose of 270 mg/m2 for cisplatin was mandatory to optimize pathological complete responses.


CONCLUSION
At least 4 cycles of cisplatin-based chemotherapy should be delivered before cystectomy. Increasing the number of cycles beyond 4 cycles does not lead to a clinically significant deterioration in renal function but without obvious gain on local control.
['Culine|Stéphane|S|', 'Harter|Valentin|V|', 'Gravis|Gwenaelle|G|', 'Fléchon|Aude|A|', 'Chevreau|Christine|C|', 'Mahammedi|Hakim|H|', 'Laguerre|Brigitte|B|', 'Guillot|Aline|A|', 'Joly|Florence|F|', 'Abadie-Lacourtoisie|Sophie|S|', 'Geoffrois|Lionnel|L|', 'Fiore|Frédéric Di|FD|', 'Roubaud|Guilhem|G|', 'Barthélémy|Philippe|P|', 'Voog|Eric|E|', 'Emambux|Sheik|S|', 'Serrate|Camille|C|', 'Saldana|Carolina|C|', 'Nguyen-Tan-Hon|Thierry|T|', 'Loriot|Yohann|Y|', 'Eymard|Jean-Christophe|JC|', 'Huillard|Olivier|O|', 'Rolland|Frédéric|F|', 'Houédé|Nadine|N|', 'Spano|Jean-Philippe|JP|', 'Demery|Mounira El|ME|', 'Vieillot|Sabine|S|', "L'Haridon|Tifenn|T|", 'Hilgers|Werner|W|', 'Allory|Yves|Y|', 'Pfister|Christian|C|', '|||']
Pathological complete response Pathological downstaging Cisplatin-based chemotherapy Neoadjuvant treatment Perioperative chemotherapy