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11.08.2023 | RESEARCH ARTICLE

Neoadjuvant chemotherapy with dose-dense MVAC in muscle-invasive bladder cancer: a tertiary center experience

verfasst von: Marina Serrano, Nerea Muñoz-Unceta, Lucía Andrea Alonso, Ainara Azueta, José Luis Gutiérrez Baños, Laura Ferreira, Mario Domínguez, Albero Torres Zurita, Roberto Ballestero, Diego Cacho, Marta López-Brea, Marta Sotelo, Félix Campos-Juanatey, Enrique Ramos Barseló, Ignacio Duran

Erschienen in: Clinical and Translational Oncology | Ausgabe 2/2024

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Abstract

Purpose

Neoadjuvant chemotherapy in muscle-invasive bladder cancer (MIBC) patients has proven beneficial in overall survival. However, the optimal regimen is still a matter of debate.

Materials and methods

In this retrospective analysis, we evaluate the results obtained in 42 patients treated in our center with 4 cycles of neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) followed by radical cystectomy from August 2015 to October 2020. All patients had cT2 or higher non-metastatic MIBC. Clinical and pathological outcomes are reported.

Results

Of the 42 patients, 90.5% were men (n = 38) and the mean age was 65 years. All of them had ECOG 0–1 at diagnosis and most tumors had an initial clinical stage T2N0 (76%). Thirty-six patients (85.7%) completed 4 cycles of neoadjuvant treatment, and 21.4% required a dose reduction. The most frequent adverse event (AE) was grade 1–2 asthenia (81%), while neutropenia was the most frequent grade 3 or higher AE (38%). Complete pathological response (ypT0, ypN0) was achieved in 50% of patients (n = 21), and down-staging was observed in 57.1% (n = 24). Only one patient presented radiological progressive disease during neoadjuvant treatment (2.4%), and after a mean follow-up time of 31.5 months, 33.3% of patients experienced disease recurrence.

Conclusions

Neoadjuvant chemotherapy with 4 cycles of dd-MVAC is an effective regimen with high rates of pathological complete responses and down-staging along with an acceptable toxicity profile. DD-MVAC should be considered as an alternative to cisplatin and gemcitabine in patients with good clinical performance status.
Literatur
2.
Zurück zum Zitat Stein JP, Lieskovsky G, Cote R, Groshen S, Feng AC, Boyd S, et al. Radical cystectomy in the treatment of invasive bladder cancer. long-term results in patients. J Clin Oncol. 2001;19(3):666–75.CrossRefPubMed Stein JP, Lieskovsky G, Cote R, Groshen S, Feng AC, Boyd S, et al. Radical cystectomy in the treatment of invasive bladder cancer. long-term results in patients. J Clin Oncol. 2001;19(3):666–75.CrossRefPubMed
3.
Zurück zum Zitat Moschini M, Karnes RJ, Sharma V, Gandaglia G, Fossati N, Dell’Oglio P, et al. Patterns and prognostic significance of clinical recurrences after radical cystectomy for bladder cancer: a 20-year single center experience. Eur J Surg Oncol. 2016;42:735–43.CrossRefPubMed Moschini M, Karnes RJ, Sharma V, Gandaglia G, Fossati N, Dell’Oglio P, et al. Patterns and prognostic significance of clinical recurrences after radical cystectomy for bladder cancer: a 20-year single center experience. Eur J Surg Oncol. 2016;42:735–43.CrossRefPubMed
4.
Zurück zum Zitat Grossman HB, Natale RB, Tangen CM, Speights VO, Vogelzand NJ, Trump DL, et al. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med. 2003;349:859–66.CrossRefPubMed Grossman HB, Natale RB, Tangen CM, Speights VO, Vogelzand NJ, Trump DL, et al. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med. 2003;349:859–66.CrossRefPubMed
5.
Zurück zum Zitat Advanced Bladder Cancer Meta-analysis Collaboration. Neoadjuvant chemotherapy in invasive bladder cancer: update of a systematic review and meta-analysis of individual patient data advanced bladder cancer meta-analysis collaboration. Eur Urol. 2005;48:202–5.CrossRef Advanced Bladder Cancer Meta-analysis Collaboration. Neoadjuvant chemotherapy in invasive bladder cancer: update of a systematic review and meta-analysis of individual patient data advanced bladder cancer meta-analysis collaboration. Eur Urol. 2005;48:202–5.CrossRef
6.
Zurück zum Zitat Yin M, Joshi M, Meijer RP, Glantz M, Holder S, Harvey HA, et al. Neoadjuvant chemotherapy for muscle-invasive bladder cancer: a systematic review and two-step meta-analysis. Oncologist. 2016;21(6):708–15.CrossRefPubMedPubMedCentral Yin M, Joshi M, Meijer RP, Glantz M, Holder S, Harvey HA, et al. Neoadjuvant chemotherapy for muscle-invasive bladder cancer: a systematic review and two-step meta-analysis. Oncologist. 2016;21(6):708–15.CrossRefPubMedPubMedCentral
7.
Zurück zum Zitat Kassouf W, Spiess PE, Brown GA, Munsell MF, Grossman HB, Siefker-Radtke A, et al. P0 stage at radical cystectomy for bladder cancer is associated with improved outcome independent of traditional clinical risk factors. Eur Urol. 2007;52:769–74.CrossRefPubMedPubMedCentral Kassouf W, Spiess PE, Brown GA, Munsell MF, Grossman HB, Siefker-Radtke A, et al. P0 stage at radical cystectomy for bladder cancer is associated with improved outcome independent of traditional clinical risk factors. Eur Urol. 2007;52:769–74.CrossRefPubMedPubMedCentral
9.
Zurück zum Zitat Petrelli F, Coinu A, Cabiddu M, Ghilardi M, Vavassori I, Barni S. Correlation of pathologic complete response with survival after neoadjuvant chemotherapy in bladder cancer treated with cystectomy: a meta-analysis. Eur Urol. 2014;65:350–7.CrossRefPubMed Petrelli F, Coinu A, Cabiddu M, Ghilardi M, Vavassori I, Barni S. Correlation of pathologic complete response with survival after neoadjuvant chemotherapy in bladder cancer treated with cystectomy: a meta-analysis. Eur Urol. 2014;65:350–7.CrossRefPubMed
11.
Zurück zum Zitat Witjes A, Bruins H, Cathomas R, Compérat EM, Cowan NC, Gakis G, et al. European Association of Urology Guidelines on Muscle-Invasive and Metastatic Bladder Cancer. Eur Urol 2020. Witjes A, Bruins H, Cathomas R, Compérat EM, Cowan NC, Gakis G, et al. European Association of Urology Guidelines on Muscle-Invasive and Metastatic Bladder Cancer. Eur Urol 2020.
13.
Zurück zum Zitat Reardon ZD, Patel SG, Zaid HB, Stimson CJ, Resnick MJ, Keegan KA, et al. Trends in the use of perioperative chemotherapy for localized and locally advanced muscle-invasive bladder cancer: a sign of changing tides. Eur Urol. 2015;67(1):165–70.CrossRefPubMed Reardon ZD, Patel SG, Zaid HB, Stimson CJ, Resnick MJ, Keegan KA, et al. Trends in the use of perioperative chemotherapy for localized and locally advanced muscle-invasive bladder cancer: a sign of changing tides. Eur Urol. 2015;67(1):165–70.CrossRefPubMed
14.
Zurück zum Zitat Lavery HJ, Stensland KD, Niegisch G, Albers P, Droller MJ. Pathological T0 following radical cystectomy with or without neo-adjuvant chemotherapy: a useful surrogate. J Urol. 2014;191(4):898–906.CrossRefPubMed Lavery HJ, Stensland KD, Niegisch G, Albers P, Droller MJ. Pathological T0 following radical cystectomy with or without neo-adjuvant chemotherapy: a useful surrogate. J Urol. 2014;191(4):898–906.CrossRefPubMed
15.
Zurück zum Zitat Choueiri TK, Jacobus S, Bellmunt J, Qu A, Appleman LJ, Tretter C, et al. Neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin and cisplatin with pegfilgrastim support in muscle invasive urothelial cancer: pathologic, radiologic and biomarker correlates. J Clin Oncol. 2014;32:1882–94.CrossRef Choueiri TK, Jacobus S, Bellmunt J, Qu A, Appleman LJ, Tretter C, et al. Neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin and cisplatin with pegfilgrastim support in muscle invasive urothelial cancer: pathologic, radiologic and biomarker correlates. J Clin Oncol. 2014;32:1882–94.CrossRef
16.
Zurück zum Zitat Pouessel D, Chevret S, Rolland F, Gravis G, Geoffrois L, Roubaud G, et al. Standard or accelerated methotrexate, vinblastine, doxorubicin and cisplatin as neoadjuvant chemotherapy for locally advanced urothelial bladder cancer: does dose intensity matter? Eur J Cancer. 2016;54:69–74.CrossRefPubMed Pouessel D, Chevret S, Rolland F, Gravis G, Geoffrois L, Roubaud G, et al. Standard or accelerated methotrexate, vinblastine, doxorubicin and cisplatin as neoadjuvant chemotherapy for locally advanced urothelial bladder cancer: does dose intensity matter? Eur J Cancer. 2016;54:69–74.CrossRefPubMed
17.
Zurück zum Zitat von der Maase H, Sengelov L, Roberts JT, Ricci S, Dogliotti L, Oliver T, et al. Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. J Clin Oncol. 2005;23(21):4602–8. https://doi.org/10.1200/JCO.2005.07.757.CrossRefPubMed von der Maase H, Sengelov L, Roberts JT, Ricci S, Dogliotti L, Oliver T, et al. Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. J Clin Oncol. 2005;23(21):4602–8. https://​doi.​org/​10.​1200/​JCO.​2005.​07.​757.CrossRefPubMed
18.
Zurück zum Zitat Zargar H, Espiritu PN, Fairey AS, Mertens LS, Dinney CP, Mir MC, et al. Multicenter assessment of neoadjuvant chemotherapy for muscle-invasive bladder cancer. Eur Urol. 2015;67(2):241–9.CrossRefPubMed Zargar H, Espiritu PN, Fairey AS, Mertens LS, Dinney CP, Mir MC, et al. Multicenter assessment of neoadjuvant chemotherapy for muscle-invasive bladder cancer. Eur Urol. 2015;67(2):241–9.CrossRefPubMed
19.
Zurück zum Zitat Galsky MD, Pal SK, Chowdhury S, Harshman LC, Crabb SJ, Wong YN, et al. Retrospective international study of cancers of the Urothelial tract (RISC) investigators. comparative effectiveness of gemcitabine plus cisplatin versus methotrexate, vinblastine, doxorubicin, plus cisplatin as neoadjuvant therapy for muscle-invasive bladder cancer. Cancer. 2015;121(15):2586–93. https://doi.org/10.1002/cncr.29387.CrossRefPubMed Galsky MD, Pal SK, Chowdhury S, Harshman LC, Crabb SJ, Wong YN, et al. Retrospective international study of cancers of the Urothelial tract (RISC) investigators. comparative effectiveness of gemcitabine plus cisplatin versus methotrexate, vinblastine, doxorubicin, plus cisplatin as neoadjuvant therapy for muscle-invasive bladder cancer. Cancer. 2015;121(15):2586–93. https://​doi.​org/​10.​1002/​cncr.​29387.CrossRefPubMed
20.
Zurück zum Zitat Plimack ER, Hoffman-Censits JH, Viterbo R, Trabulsi EJ, Ross EA, Greenberg RE, et al. Accelerated methotrexate, vinblastine, doxorubicin and cisplatin is safe effective and efficient neoadjuvant treatment for muscle invasive bladder cancer results of a multicenter phase II study with molecular correlates of response and toxicity. J Clin Oncol. 2014;32:1895–901.CrossRefPubMedPubMedCentral Plimack ER, Hoffman-Censits JH, Viterbo R, Trabulsi EJ, Ross EA, Greenberg RE, et al. Accelerated methotrexate, vinblastine, doxorubicin and cisplatin is safe effective and efficient neoadjuvant treatment for muscle invasive bladder cancer results of a multicenter phase II study with molecular correlates of response and toxicity. J Clin Oncol. 2014;32:1895–901.CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Zargar H, Shah JB, Van Rhijn BW, Daneshmand S, Bivalacqua TJ, Spiess PE, et al. Neoadjuvant dose dense MVAC versus gemcitabine and cisplatin in patients with cT3-4a N0M0 bladder cancer treated with radical cystectomy. J Urol. 2018;199:1452–8.CrossRefPubMed Zargar H, Shah JB, Van Rhijn BW, Daneshmand S, Bivalacqua TJ, Spiess PE, et al. Neoadjuvant dose dense MVAC versus gemcitabine and cisplatin in patients with cT3-4a N0M0 bladder cancer treated with radical cystectomy. J Urol. 2018;199:1452–8.CrossRefPubMed
22.
Zurück zum Zitat Pfister C, Gravis G, Flechon A, Soulié M, Guy L, Laguerre B, et al. Dose-dense methotrexate, vinblastine, doxorubicin and cisplatin (dd-MVAC) or gemcitabine and cisplatin (GC) as perioperative chemotherapy for patients with muscle-invasive bladder cancer (MIBC): Results of the GETUG/AFU VESPER V05 phase III trial. ESMO Congress 2021 (16–21 September). Pfister C, Gravis G, Flechon A, Soulié M, Guy L, Laguerre B, et al. Dose-dense methotrexate, vinblastine, doxorubicin and cisplatin (dd-MVAC) or gemcitabine and cisplatin (GC) as perioperative chemotherapy for patients with muscle-invasive bladder cancer (MIBC): Results of the GETUG/AFU VESPER V05 phase III trial. ESMO Congress 2021 (16–21 September).
23.
Zurück zum Zitat Brant A, Kates M, Chappidi MR, Patel HD, Sopko NA, Netto GJ, et al. Pathologic response in patients receiving neoadjuvant chemotherapy for muscle-invasive bladder cancer: Is therapeutic effect owing to chemotherapy or TURBT? Urologic Oncology: Seminars Original Investigations. 2017;35(34):e17-34.e25. Brant A, Kates M, Chappidi MR, Patel HD, Sopko NA, Netto GJ, et al. Pathologic response in patients receiving neoadjuvant chemotherapy for muscle-invasive bladder cancer: Is therapeutic effect owing to chemotherapy or TURBT? Urologic Oncology: Seminars Original Investigations. 2017;35(34):e17-34.e25.
24.
Zurück zum Zitat Mmeje CO, Benson CR, Nogueras-González GM, Jayaratna IS, Gao J, Siefker-Radtke AO, et al. Determining the optimal time for radical cystectomy after neoadjuvant chemotherapy. BJU Int. 2018;122(1):89–98.CrossRefPubMed Mmeje CO, Benson CR, Nogueras-González GM, Jayaratna IS, Gao J, Siefker-Radtke AO, et al. Determining the optimal time for radical cystectomy after neoadjuvant chemotherapy. BJU Int. 2018;122(1):89–98.CrossRefPubMed
25.
Zurück zum Zitat Rouanne M, Bajorin DF, Hannan R, Galsky MD, Williams SB, Necchi A, et al. Rationale and outcomes for neoadjuvant immunotherapy in urothelial carcinoma of the bladder. Eur Urol Oncol. 2020;3(6):728–38.CrossRefPubMed Rouanne M, Bajorin DF, Hannan R, Galsky MD, Williams SB, Necchi A, et al. Rationale and outcomes for neoadjuvant immunotherapy in urothelial carcinoma of the bladder. Eur Urol Oncol. 2020;3(6):728–38.CrossRefPubMed
Metadaten
Titel
Neoadjuvant chemotherapy with dose-dense MVAC in muscle-invasive bladder cancer: a tertiary center experience
verfasst von
Marina Serrano
Nerea Muñoz-Unceta
Lucía Andrea Alonso
Ainara Azueta
José Luis Gutiérrez Baños
Laura Ferreira
Mario Domínguez
Albero Torres Zurita
Roberto Ballestero
Diego Cacho
Marta López-Brea
Marta Sotelo
Félix Campos-Juanatey
Enrique Ramos Barseló
Ignacio Duran
Publikationsdatum
11.08.2023
Verlag
Springer International Publishing
Erschienen in
Clinical and Translational Oncology / Ausgabe 2/2024
Print ISSN: 1699-048X
Elektronische ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-023-03277-4

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