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Clinical Trial
. 2021 Dec;19(6):554-562.
doi: 10.1016/j.clgc.2021.08.005. Epub 2021 Sep 8.

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

Stéphane Culine  1 , Valentin Harter  2 , Gwenaelle Gravis  3 , Aude Fléchon  4 , Christine Chevreau  5 , Hakim Mahammedi  6 , Brigitte Laguerre  7 , Aline Guillot  8 , Florence Joly  9 , Sophie Abadie-Lacourtoisie  10 , Lionnel Geoffrois  11 , Frédéric Di Fiore  12 , Guilhem Roubaud  13 , Philippe Barthélémy  14 , Eric Voog  15 , Sheik Emambux  16 , Camille Serrate  17 , Carolina Saldana  18 , Thierry Nguyen-Tan-Hon  19 , Yohann Loriot  20 , Jean-Christophe Eymard  21 , Olivier Huillard  22 , Frédéric Rolland  23 , Nadine Houédé  24 , Jean-Philippe Spano  25 , Mounira El Demery  26 , Sabine Vieillot  27 , Tifenn L'Haridon  28 , Werner Hilgers  29 , Yves Allory  30 , Christian Pfister  31 ; VESPER Trial Investigators
Affiliations
Clinical Trial

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

Stéphane Culine et al. Clin Genitourin Cancer. 2021 Dec.

Abstract

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.

Keywords: Cisplatin-based chemotherapy; Neoadjuvant treatment; Pathological complete response; Pathological downstaging; Perioperative chemotherapy.

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