Multicenter prospective phase II trial of neoadjuvant dose-dense gemcitabine plus cisplatin in patients with muscle-invasive bladder cancer Journal Article


Authors: Iyer, G.; Balar, A. V.; Milowsky, M. I.; Bochner, B. H.; Dalbagni, G.; Donat, S. M.; Herr, H. W.; Huang, W. C.; Taneja, S. S.; Woods, M.; Ostrovnaya, I.; Al-Ahmadie, H.; Arcila, M. E.; Riches, J. C.; Meier, A.; Bourque, C.; Shady, M.; Won, H.; Rose, T. L.; Kim, W. Y.; Kania, B. E.; Boyd, M. E.; Cipolla, C. K.; Regazzi, A. M.; Delbeau, D.; McCoy, A. S.; Vargas, H. A.; Berger, M. F.; Solit, D. B.; Rosenberg, J. E.; Bajorin, D. F.
Article Title: Multicenter prospective phase II trial of neoadjuvant dose-dense gemcitabine plus cisplatin in patients with muscle-invasive bladder cancer
Abstract: Purpose Neoadjuvant chemotherapy followed by radical cystectomy (RC) is a standard of care for the management of muscle-invasive bladder cancer (MIBC). Dose-dense cisplatin-based regimens have yielded favorable outcomes compared with standard-dose chemotherapy, yet the optimal neoadjuvant regimen remains undefined. We assessed the efficacy and tolerability of six cycles of neoadjuvant dose-dense gemcitabine and cisplatin (ddGC) in patients with MIBC. Patients and Methods In this prospective, multicenter phase II study, patients received ddGC (gemcitabine 2,500 mg/m2 on day 1 and cisplatin 35 mg/m2 on days 1 and 2) every 2 weeks for 6 cycles followed by RC. The primary end point was pathologic downstaging to non–muscle-invasive disease (, pT2N0). Patients who did not undergo RC were deemed nonresponders. Pretreatment tumors underwent next-generation sequencing to identify predictors of chemosensitivity. Results Forty-nine patients were enrolled from three institutions. The primary end point was met, with 57% of 46 evaluable patients downstaged to, pT2N0. Pathologic response correlated with improved recurrence-free survival and overall survival. Nineteen patients (39%) required toxicity-related dose modifications. Sixty-seven percent of patients completed all six planned cycles. No patient failed to undergo RC as a result of chemotherapy-associated toxicities. The most frequent treatment-related toxicity was anemia (12%; grade 3). The presence of a presumed deleterious DNA damage response (DDR) gene alteration was associated with chemosensitivity (positive predictive value for, pT2N0 [89%]). No patient with a deleterious DDR gene alteration has experienced recurrence at a median follow-up of 2 years. Conclusion Six cycles of ddGC is an active, well-tolerated neoadjuvant regimen for the treatment of patients with MIBC. The presence of a putative deleterious DDR gene alteration in pretreatment tumor tissue strongly predicted for chemosensitivity, durable response, and superior long-term survival. © 2018 by American Society of Clinical Oncology
Journal Title: Journal of Clinical Oncology
Volume: 36
Issue: 19
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2018-07-01
Start Page: 1949
End Page: 1956
Language: English
DOI: 10.1200/jco.2017.75.0158
PROVIDER: scopus
PUBMED: 29742009
PMCID: PMC6049398
DOI/URL:
Notes: Article -- Export Date: 1 August 2018 -- Source: Scopus
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MSK Authors
  1. Dean Bajorin
    505 Bajorin
  2. Guido Dalbagni
    270 Dalbagni
  3. Sherri M Donat
    138 Donat
  4. David Solit
    538 Solit
  5. Gopakumar Vasudeva Iyer
    166 Iyer
  6. Bernard Bochner
    359 Bochner
  7. Michael Forman Berger
    495 Berger
  8. Maria Eugenia Arcila
    455 Arcila
  9. Harry W Herr
    485 Herr
  10. Ashley Regazzi
    46 Regazzi
  11. Helen Hyeong-Eun Won
    90 Won
  12. Jamie C Riches
    23 Riches
  13. Jonathan Eric Rosenberg
    294 Rosenberg
  14. Mariel Elena Boyd
    12 Boyd
  15. Asia S McCoy
    11 McCoy
  16. Brooke Elizabeth Kania
    7 Kania
  17. Andreas Alexander Meier
    5 Meier
  18. Maha Shady
    7 Shady