Advertisement

World Journal of Urology

, Volume 34, Issue 2, pp 157–162 | Cite as

Neoadjuvant induction dose-dense MVAC for muscle invasive bladder cancer: efficacy and safety compared with classic MVAC and gemcitabine/cisplatin

  • Elisabeth E. Fransen van de Putte
  • Laura S. Mertens
  • Richard P. Meijer
  • Michiel S. van der Heijden
  • Axel Bex
  • Henk G. van der Poel
  • J. Martijn Kerst
  • Andries M. Bergman
  • Simon Horenblas
  • Bas W. G. van Rhijn
Original Article

Abstract

Purpose

To investigate the efficacy and safety of neoadjuvant induction dose-dense MVAC (dd-MVAC) for muscle invasive bladder cancer (MIBC). Results of the 2-week-per-cycle regimen were compared with classic MVAC (4 weeks per cycle) and gemcitabine/cisplatin (GC, 3 weeks per cycle).

Methods

We included 166 patients with non-organ-confined MIBC, who received neoadjuvant induction dd-MVAC (80), classic MVAC (35), or GC (51) between 1990 and 2014. Complete pathological response (pCR) was defined as no evidence of residual tumor in cystectomy and lymphadenectomy specimens (ypT0N0). pCR and toxicity rates were compared among regimens.

Results

pCR was found in 29 % of dd-MVAC-treated patients, which was not significantly different from classic MVAC (20 %, p = 0.366) and GC (32 %, p = 0.845). Grade 3–4 toxicity rates related to dd-MVAC and GC (44 %) were similar (p = 0.202), whereas the toxicity rate for classic MVAC (55 %) was significantly higher than for dd-MVAC (32 %) uncorrected (p = 0.026) and corrected for patient and tumor characteristics (OR 2.84, p = 0.037).

Conclusions

Neoadjuvant induction dd-MVAC resulted in pathological response rates similar to classic MVAC and GC treatment in patients with non-organ-confined MIBC. The shorter cycle duration compared with classic MVAC and GC and the significantly lower toxicity rate compared with classic MVAC indicate that dd-MVAC should be the preferred option for neoadjuvant induction treatment.

Keywords

Bladder cancer Neoadjuvant chemotherapy Dose dense MVAC Cisplatin 

Notes

Compliance with Ethical Standards

Ethical standard

For this type of study, formal consent is not required.

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Advanced Bladder Cancer (ABC) Meta-analysis Collaboration (2005) Neoadjuvant chemotherapy in invasive bladder cancer: update of a systematic review and meta-analysis of individual patient data. Eur Urol 48:202–206CrossRefGoogle Scholar
  2. 2.
    Sherif A, Holmberg L, Rintala E et al (2004) Neoadjuvant cisplatinum based combination chemotherapy in patients with invasive bladder cancer: a combined analysis of two Nordic studies. Eur Urol 45:297–303CrossRefPubMedGoogle Scholar
  3. 3.
    International Collaboration of Trialists on behalf of the Medical Research Council Advanced Bladder Cancer Working Party (now the National Cancer Research Institute Bladder Cancer Clinical Studies Group), the European Organisation for Research and Treatment of Cancer Genito-Urinary Tract Cancer Group, the Australian Bladder Cancer Study Group, et al. (2011) International phase III trial assessing neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: long-term results of the BA06 30894 Trial. J Clin Oncol 29:2171–7Google Scholar
  4. 4.
    Fedeli U, Fedewa SA, Ward EM (2011) Treatment of muscle invasive bladder cancer: evidence from the National Cancer Database, 2003–2007. J Urol 185:72–78CrossRefPubMedGoogle Scholar
  5. 5.
    David KA, Milowsky MI, Ritchey J et al (2007) Low incidence of perioperative chemotherapy for stage III bladder cancer 1998–2003: a report from the National Cancer Data Base. J Urol 178:451–454CrossRefPubMedGoogle Scholar
  6. 6.
    Porter MP, Kerrigan MC, Donato BMK et al (2011) Patterns of use of systemic chemotherapy for Medicare beneficiaries with urothelial bladder cancer. Urol Oncol 29:252–258CrossRefPubMedGoogle Scholar
  7. 7.
    Sternberg CN, de Mulder PH, van Oosterom AT et al (1993) Escalated M-VAC chemotherapy and recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) in patients with advanced urothelial tract tumors. Ann Oncol 4:403–407PubMedGoogle Scholar
  8. 8.
    Sternberg C, de Mulder PH, Schornagel JH et al (2001) Randomized Phase III trial of high–dose-intensity methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) chemotherapy and recombinant human granulocyte colony-stimulating factor. J Clin Oncol 19:2638–2646PubMedGoogle Scholar
  9. 9.
    Culp SH, Dickstein RJ, Grossman HB et al (2015) Refining patient selection for neoadjuvant chemotherapy before radical cystectomy. J Urol 191:40–47CrossRefGoogle Scholar
  10. 10.
    Galsky MD, Hahn NM, Rosenberg J et al (2011) A consensus definition of patients with metastatic urothelial carcinoma who are unfit for cisplatin-based chemotherapy. Lancet Oncol 12:211–214CrossRefPubMedGoogle Scholar
  11. 11.
    Sobin L, Gospodarowicz M, Wittekind C (2009) Urological tumours, urinary bladder. In: Sobin L, Gospodarowicz M, Wittekind C (eds) TNM classification of malignant tumors, 7th edn. Wiley, New York, pp 262–265Google Scholar
  12. 12.
    Plimack ER, Hoffman-Censits JH, Viterbo R et al (2014) 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 32:1895–1901PubMedCentralCrossRefPubMedGoogle Scholar
  13. 13.
    Choueiri TK, Jacobus S, Bellmunt J et al (2014) Neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin with pegfilgrastim support in muscle-invasive urothelial cancer: pathologic, radiologic, and biomarker correlates. J Clin Oncol 32:1889–1894CrossRefPubMedGoogle Scholar
  14. 14.
    Blick C, Hall P, Pwint T et al (2012) Accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC) as neoadjuvant chemotherapy for patients with muscle-invasive transitional cell carcinoma of the bladder. Cancer 118:3920–3927CrossRefPubMedGoogle Scholar
  15. 15.
    Rosenblatt R, Sherif A, Rintala E et al (2012) Pathologic downstaging is a surrogate marker for efficacy and increased survival following neoadjuvant chemotherapy and radical cystectomy for muscle-invasive urothelial bladder cancer. Eur Urol 61:1229–1238CrossRefPubMedGoogle Scholar
  16. 16.
    Meijer RP, Nieuwenhuijzen JA, Meinhardt W et al (2013) Response to induction chemotherapy and surgery in non-organ confined bladder cancer: a single institution experience. Eur J Surg Oncol 39:365–371CrossRefPubMedGoogle Scholar
  17. 17.
    von der Maase H, Hansen SW, Roberts JT et al (2000) Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol 18:3068–3077PubMedGoogle Scholar
  18. 18.
    von der Maase H, Sengelov L, Roberts JT et al (2005) 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 23:4602–4608CrossRefPubMedGoogle Scholar
  19. 19.
    Zargar H, Espiritu PN, Fairey AS et al (2015) Multicenter assessment of neoadjuvant chemotherapy for muscle-invasive bladder cancer. Eur Urol 67:241–249CrossRefPubMedGoogle Scholar
  20. 20.
    Pouessel D, Gauthier H, Serrate C et al (2014) Dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin neoadjuvant chemotherapy in bladder cancer: ready for prime time? J Clin Oncol 32:4168–4169CrossRefPubMedGoogle Scholar
  21. 21.
    Meijer RP, Mertens LS, van Rhijn BWG et al (2014) Induction chemotherapy followed by surgery in node positive bladder cancer. Urology 83:134–139CrossRefPubMedGoogle Scholar
  22. 22.
    Nieuwenhuijzen JA, Bex A, Meinhardt W et al (2005) Neoadjuvant methotrexate, vinblastine, doxorubicin and cisplatin for histologically proven lymph node positive bladder cancer. J Urol 174:80–85CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Elisabeth E. Fransen van de Putte
    • 1
  • Laura S. Mertens
    • 1
  • Richard P. Meijer
    • 1
    • 2
  • Michiel S. van der Heijden
    • 3
  • Axel Bex
    • 1
  • Henk G. van der Poel
    • 1
  • J. Martijn Kerst
    • 3
  • Andries M. Bergman
    • 3
  • Simon Horenblas
    • 1
  • Bas W. G. van Rhijn
    • 1
  1. 1.Department of UrologyThe Netherlands Cancer Institute-Antoni van Leeuwenhoek HospitalAmsterdamThe Netherlands
  2. 2.Department of UrologyUniversity Medical Center UtrechtUtrechtThe Netherlands
  3. 3.Department of Medical OncologyThe Netherlands Cancer Institute-Antoni van Leeuwenhoek HospitalAmsterdamThe Netherlands

Personalised recommendations