medwireNews: A phase 2 trial has demonstrated the promising efficacy and tolerability of neoadjuvant gemcitabine plus split-dose cisplatin in patients with localised high-grade upper tract urothelial carcinoma (UTUC).
Almost two-thirds of study participants had a pathological response and all were able to proceed to surgery, report the researchers in the Journal of Clinical Oncology.
They note that these outcomes are “superior” to those of historical series and “there are no completed randomized controlled phase III neoadjuvant trials at this time” in this rare disease setting.
Therefore, “[t]hese results lend significant support to the consideration of [neoadjuvant chemotherapy] as a standard of care to allow for expansion of perioperative cisplatin-based chemotherapy to more patients with UTUC, and split-dose [gemcitabine–cisplatin] is a viable option for [neoadjuvant chemotherapy]”, writes the team.
In the multicentre study, 57 patients with localised high-grade disease received up to four 21-day cycles of gemcitabine 1000 mg/m2 and cisplatin 35 mg/m2 given on days 1 and 8, with the majority (89%) able to receive at least three full cycles and 47% all four cycles.
Nine percent of patients had a dose delay due to toxicity, 21% needed a dose reduction and 14% discontinued treatment prematurely.
Treatment-related adverse events (TRAEs) of grade 3 or worse occurred in 74% of participants, with the most common being decreases in lymphocyte and neutrophil counts, in 33% and 32%, respectively. But there were no deaths due to TRAEs and all patients were able to undergo surgery.
Jonathan Coleman (Memorial Sloan Kettering Cancer Center, New York, USA) and co-investigators also highlight that “[r]enal function was minimally affected during chemotherapy”, with median estimated glomerular filtration rates of 72% and 70% at baseline and after chemotherapy, respectively.
The primary endpoint of the study was pathological response after neoadjuvant treatment (defined as < ypT2N0) – this was achieved by 63% of patients and “met the prespecified criteria to be considered promising”, say the investigators.
A total of 19% of patients had a complete pathological response, and the 2- and 5-year progression-free survival rates were 89% and 72%, respectively, with corresponding overall survival rates of 93% and 79%.
Describing the survival rates as “excellent”, Coleman and colleagues conclude that their findings “offer support that neoadjuvant split-dose [gemcitabine–cisplatin] has substantial activity in UTUC.”
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