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.

Published on Sep 8, 2021in Clinical Genitourinary Cancer2.872
· DOI :10.1016/J.CLGC.2021.08.005
Stéphane Culine57
Estimated H-index: 57
Valentin Harter2
Estimated H-index: 2
+ 29 AuthorsSophie Abadie-Lacourtoisie12
Estimated H-index: 12
Abstract null null Background null : 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. null null null Patients and Methods null : 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 ( null null null Results null : A total of 2,128 cycles of chemotherapy were delivered, including 2,120 (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 two regimens during the first four cycles. A mild decrease occurred thereafter in patients treated with two additional cycles of dd-MVAC. A minimum total dose of 270 mg/m2 for cisplatin was mandatory to optimize pathological complete responses. null null null Conclusion null : 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. null null null MicroAbstractCGC null : A deep analysis of data from a randomized trial of perioperative chemotherapy in muscle-invasive bladder cancer shows that a minimum number of 4 cycles is required to optimize the chances of pathological complete response at cystectomy. Increasing the number beyond 4 cycles does not lead to a clinically significant deterioration in renal function without any obvious gain on pathological complete response.
Abstract Background Perioperative chemotherapy (neoadjuvant or adjuvant) has been developed to increase overall survival for nonmetastatic muscle-invasive bladder cancer (MIBC). Retrospective studies or prospective phase II trials have been reported to use dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) or gemcitabine and cisplatin (GC). As dd-MVAC has shown higher response rates in metastatic disease, better efficacy is expected in the perioperative setting. Objective...
#5Culine SH-Index: 1
#1Gopa Iyer (Cornell University)H-Index: 33
#3Emily C. Zabor (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 30
Last. Dean F. Bajorin (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 97
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Abstract Introduction To determine drug delivery/toxicity, and pathological/surgical outcomes of muscle-invasive bladder cancer (MIBC) patients receiving neoadjuvant gemcitabine-cisplatin (GC) plus radical cystectomy-pelvic lymph node dissection (RC-PLND). Patients and Methods Chemotherapy and surgical/pathologic outcomes were retrospectively analyzed with 5-year survival follow-up at a referral center. Post-neoadjuvant chemotherapy (NAC) pathologic endpoints included complete response (pT0N0), ...
#1Timothy D. Lyon (Mayo Clinic)H-Index: 12
#2Igor Frank (Mayo Clinic)H-Index: 63
Last. Matthew K. Tollefson (Mayo Clinic)H-Index: 35
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Abstract Introduction The objective of the study was to determine whether sarcopenia is associated with pathologic and survival outcomes for patients with muscle-invasive bladder cancer (MIBC) treated with neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC). Patients and Methods We identified MIBC patients treated with cisplatin-based NAC in our cystectomy registry from 2000 to 2016. Pre- and post-NAC computed tomography images were analyzed with BodyCompSlicer, a validated body c...
#1Charles C. PeytonH-Index: 10
#2Dominic H. TangH-Index: 13
Last. Scott M. GilbertH-Index: 27
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Importance Neoadjuvant chemotherapy (NAC) followed by radical cystectomy improves survival compared with cystectomy alone for patients with bladder cancer. Although gemcitabine with cisplatin has become a standard NAC regimen, a dose-dense combination of methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) is being adopted at some institutions. Objective To assess the association of neoadjuvant ddMVAC vs standard regimens with downstaging and overall survival among patients treated wit...
#2Jay B. Shah (University of Texas MD Anderson Cancer Center)H-Index: 22
#4Sia Daneshmand (SC: University of Southern California)H-Index: 9
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Purpose: Level I evidence supports the usefulness of neoadjuvant cisplatin based chemotherapy for muscle invasive bladder cancer. Since dose dense MVAC (methotrexate, vinblastine, doxorubicin and cisplatin) has mostly replaced traditional MVAC, we compared pathological response and survival rates in patients with locally advanced bladder cancer who received neoadjuvant chemotherapy with dose dense MVAC vs gemcitabine and cisplatin.Materials and Methods: We retrospectively reviewed the records of...
#1Stangl-Kremser (Medical University of Vienna)H-Index: 1
#2Andrea MariH-Index: 32
Last. Tobias KlatteH-Index: 31
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PURPOSE: We hypothesized sarcopenia as predictive factor as a response to upfront chemotherapy of muscle-invasive urothelial bladder cancer (MIBC). METHODS: We retrospectively studied 30 patients who received upfront cisplatin-based chemotherapy for MIBC (pT2-4 N0/+ M0) before planned radical cystectomy. Skeletal muscle index (SMI) was calculated by CT at study baseline and following completion of chemotherapy. Patients were stratified according to the presence of sarcopenia. Endpoints included ...
#1Elizabeth R. Plimack (Fox Chase Cancer Center)H-Index: 65
#2Jean H. Hoffman-Censits (Thomas Jefferson University)H-Index: 21
Last. Gary R. Hudes (Fox Chase Cancer Center)H-Index: 61
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Purpose Neoadjuvant cisplatin-based chemotherapy is standard of care for muscle-invasive bladder cancer (MIBC); however, it is infrequently adopted in practice because of concerns regarding toxicity and delay to cystectomy. We hypothesized that three cycles of neoadjuvant accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC) would be safe, shorten the time to surgery, and yield similar pathologic complete response (pT0) rates compared with historical controls. Patients and Me...
#1Anna Spathis (St George's, University of London)H-Index: 10
#2Kate Fife (St George's, University of London)H-Index: 4
Last. Bee WeeH-Index: 24
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Purpose Fatigue is a distressing symptom occurring in more than 60% of patients with cancer. The CNS stimulants modafinil and methylphenidate are recommended for the treatment of cancer-related fatigue, despite a limited evidence base. We aimed to evaluate the efficacy and tolerability of modafinil in the management of fatigue in patients with non–small-cell lung cancer (NSCLC). Patients and Methods Adults with advanced NSCLC and performance status of 0 to 2, who were not treated with chemothera...
#1Toni K. Choueiri (Harvard University)H-Index: 120
#2Susanna Jacobus (Lahey Hospital & Medical Center)H-Index: 1
Last. Jonathan E. Rosenberg (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 66
view all 19 authors...
Purpose In advanced urothelial cancer, treatment with dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) results in a high response rate, less toxicity, and few dosing delays. We explored the efficacy and safety of neoadjuvant ddMVAC with pegfilgrastim support in muscle-invasive urothelial cancer (MIUC). Patients and Methods Patients with cT2-cT4, N0-1, M0 MIUC were enrolled. Four cycles of ddMVAC were administered, followed by radical cystectomy. The primary end point was...
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