Multicenter Phase II Clinical Trial of Gemcitabine and Cisplatin as Neoadjuvant Chemotherapy for Patients With High-Grade Upper Tract Urothelial Carcinoma.

Authors

Jonathan A Coleman, Memorial Sloan Kettering Cancer Center
Wesley Yip, Memorial Sloan Kettering Cancer Center
Nathan C Wong, Memorial Sloan Kettering Cancer Center
Daniel D Sjoberg, Memorial Sloan Kettering Cancer Center
Bernard H Bochner, Memorial Sloan Kettering Cancer Center
Guido Dalbagni, Memorial Sloan Kettering Cancer Center
S Machele Donat, Memorial Sloan Kettering Cancer Center
Harry W Herr, Memorial Sloan Kettering Cancer Center
Eugene K Cha, Memorial Sloan Kettering Cancer Center
Timothy F Donahue, Memorial Sloan Kettering Cancer Center
Eugene J Pietzak, Memorial Sloan Kettering Cancer Center
A Ari Hakimi, Memorial Sloan Kettering Cancer Center
Kwanghee Kim, Memorial Sloan Kettering Cancer Center
Hikmat A Al-Ahmadie, Memorial Sloan Kettering Cancer Center
H Alberto Vargas, Memorial Sloan Kettering Cancer Center
Ricardo G Alvim, Memorial Sloan Kettering Cancer Center
Soleen Ghafoor, Memorial Sloan Kettering Cancer Center
Nicole E Benfante, Memorial Sloan Kettering Cancer Center
Anoop M Meraney, Hartford Hospital
Steven J Shichman, Hartford Hospital
Jeffrey M Kamradt, Hartford Hospital
Suresh G. Nair MD, Lehigh Valley Health NetworkFollow
Angelo A. Baccala MD, Lehigh Valley Health NetworkFollow
Paul Palyca MD, Lehigh Valley Health NetworkFollow
Bradley Lash MD, Lehigh Valley Health NetworkFollow
Muhammad A. Rizvi MD, Lehigh Valley Health NetworkFollow
Scott K Swanson, Mayo Clinic Cancer Center
Antonio F Muina, Miami Cancer Institute
Andrea B Apolo, National Cancer Institute
Gopa Iyer, Memorial Sloan Kettering Cancer Center
Jonathan E Rosenberg, Memorial Sloan Kettering Cancer Center
Min Y Teo, Memorial Sloan Kettering Cancer Center
Dean F Bajorin, Memorial Sloan Kettering Cancer Center

Publication/Presentation Date

1-5-2023

Abstract

PURPOSE: Neoadjuvant chemotherapy (NAC) has proven survival benefits for patients with invasive urothelial carcinoma of the bladder, yet its role for upper tract urothelial carcinoma (UTUC) remains undefined. We conducted a multicenter, single-arm, phase II trial of NAC with gemcitabine and split-dose cisplatin (GC) for patients with high-risk UTUC before extirpative surgery to evaluate response, survival, and tolerability.

METHODS: Eligible patients with defined criteria for high-risk localized UTUC received four cycles of split-dose GC before surgical resection and lymph node dissection. The primary study end point was rate of pathologic response (defined as < ypT2N0). Secondary end points included progression-free survival (PFS), overall survival (OS), and safety and tolerability.

RESULTS: Among 57 patients evaluated, 36 (63%) demonstrated pathologic response (95% CI, 49 to 76). A complete pathologic response (ypT0N0) was noted in 11 patients (19%). Fifty-one patients (89%) tolerated at least three complete cycles of split-dose GC, 27 patients (47%) tolerated four complete cycles, and all patients proceeded to surgery. With a median follow up of 3.1 years, 2- and 5-year PFS rates were 89% (95% CI, 81 to 98) and 72% (95% CI, 59 to 87), while 2- and 5-year OS rates were 93% (95% CI, 86 to 100) and 79% (95% CI, 67 to 94), respectively. Pathologic complete and partial responses were associated with improved PFS and OS compared with nonresponders (≥ ypT2N any; 2-year PFS 100% and 95%

CONCLUSION: NAC with split-dose GC for high-risk UTUC is a well-tolerated, effective therapy demonstrating evidence of pathologic response that is associated with favorable survival outcomes. Given that these survival outcomes are superior to historical series, these data support the use of NAC as a standard of care for high-risk UTUC, and split-dose GC is a viable option for NAC.

First Page

2200763

Last Page

2200763

ISSN

1527-7755

Disciplines

Medicine and Health Sciences

PubMedID

36603175

Department(s)

Department of Medicine, Hematology-Medical Oncology Division

Document Type

Article

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