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.

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.

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.

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.

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.

Clinical genitourinary cancer. 2021 Sep 08 [Epub ahead of print]

Stéphane Culine, Valentin Harter, Gwenaelle Gravis, Aude Fléchon, Christine Chevreau, Hakim Mahammedi, Brigitte Laguerre, Aline Guillot, Florence Joly, Sophie Abadie-Lacourtoisie, Lionnel Geoffrois, Frédéric Di Fiore, Guilhem Roubaud, Philippe Barthélémy, Eric Voog, Sheik Emambux, Camille Serrate, Carolina Saldana, Thierry Nguyen-Tan-Hon, Yohann Loriot, Jean-Christophe Eymard, Olivier Huillard, Frédéric Rolland, Nadine Houédé, Jean-Philippe Spano, Mounira El Demery, Sabine Vieillot, Tifenn L'Haridon, Werner Hilgers, Yves Allory, Christian Pfister, VESPER Trial Investigators

Department of Medical Oncology, Saint-Louis Hospital, AP-HP, Faculté de Paris, France. Electronic address: ., North-West Canceropole Data Center, Baclesse Cancer Center, Caen, France., Department of Medical Oncology, Paoli-Calmette Institute, Marseille, France., Department of Medical Oncology, Léon Bérard Cancer Center, Lyon, France., Department of Medical Oncology, ICR-IUCT Oncopole, Toulouse, France., Department of Medical Oncology, Jean Perrin Cancer Center, Clermont-Ferrand, France., Department of Medical Oncology, Eugène Marquis Cancer Center, Rennes, France., Department of Medical Oncology, Lucien Neuwirth Cancer Institute, St Priest en Jarez, France., Department of Medical Oncology, Baclesse Cancer Center, Caen, France., Department of Medical Oncology, Institut de cancérologie de l'Ouest, Angers, France., Department of Medical Oncology, Lorraine-Alexis Vautrin Cancer Institute, Nancy, France., Digestive and uro-oncology Unit, Charles Nicolle University Hospital, Rouen, France., Department of Medical Oncology, Bergonié Institute, Bordeaux, France., Department of Medical Oncology, University Hospital, Strasbourg, France., Victor Hugo Clinic, Le Mans, France., Department of Medical Oncology, University Hospital, Poitiers, France., Department of Medical Oncology, Diaconesses Croix Saint-Simon Hospital, Paris, France., Department of Medical Oncology, Henri Mondor University Hospital, AP-HP, Créteil, France., Department of Medical Oncology, University Hospital, Besançon, France., Department of Cancer Medicine, Gustave Roussy, Inserm U981, Villejuif, France., Department of Medical Oncology, Jean Godinot Institute, Reims, France., Department of Medical Oncology, Cochin Port-Royal University Hospital, AP-HP Centre, Paris, France., Department of Medical Oncology, West County Cancer Institute, Nantes, France., Gard Cancer Institute, University Hospital, Nîmes, Inserm U1194 Montpellier Cancer Institute, Montpellier University, Nimes, France., Department of Medical Oncology, Pitié Salpétrière University Hospital, AP-HP-SU, IUC, Paris, France., Department of Oncology, Cap d'Or Clinic, La Seyne sur Mer, France., Department of Oncology, Saint-Pierre Clinic, Perpignan, France., Department of Medical Oncology, Vendée Regional Hospital, La Roche-sur-Yon, France., Uro-Oncology Unit, Sainte Catherine Institute, Avignon, France., Department of Pathology, Curie Institute, Saint-Cloud, France., Department of Urology and Clinical Investigation Center, Inserm 1404, Charles Nicolle University Hospital, Rouen, France.

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