The following is a summary of “Multicenter Phase II Clinical Trial of Gemcitabine and Cisplatin as Neoadjuvant Chemotherapy for Patients With High-Grade Upper Tract Urothelial Carcinoma,” published in the March 2023 issue of Oncology by Coleman, et al.

For a study, researchers sought to evaluate the response, survival, and tolerability of neoadjuvant chemotherapy (NAC) with gemcitabine and split-dose cisplatin (GC) for patients with high-risk upper tract urothelial carcinoma (UTUC) before extirpative surgery.

The multicenter, single-arm, phase II trial included 57 eligible patients with defined criteria for high-risk localized UTUC who received four cycles of split-dose GC before surgical resection and lymph node dissection. The primary endpoint was the pathologic response rate (defined as < ypT2N0). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety and tolerability.

Of the 57 patients evaluated, 36 (63%) demonstrated a pathologic response (95% CI, 49 to 76), with 11 patients (19%) showing a complete pathologic response (ypT0N0). The treatment was well-tolerated, as 89% of patients tolerated at least three complete cycles of split-dose GC, 47% tolerated four complete cycles, and all patients proceeded to surgery. After a median follow-up of 3.1 years, the 2- and 5-year PFS rates were 89% (95% CI, 81 to 98) and 72% (95% CI, 59 to 87), while the 2- and 5-year OS rates were 93% (95% CI, 86 to 100) and 79% (95% CI, 67 to 94), respectively. In addition, pathologic complete and partial responses were associated with improved PFS and OS compared with nonresponders (≥ ypT2N any; 2-year PFS 100% and 95% vs. 76%, P < .001; 2-year OS 100% and 100% vs. 80%, P < .001).

NAC with split-dose GC for high-risk UTUC was an effective and well-tolerated therapy that demonstrated evidence of pathologic response, which is associated with favorable survival outcomes. The study supported the use of NAC as a standard of care for high-risk UTUC, and split-dose GC is a viable option for NAC, given the superior survival outcomes compared to the historical series.

Reference: ascopubs.org/doi/full/10.1200/JCO.22.00763