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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