HDCN Abstract:  ASN Annual Meeting 2020 -- Digital Meeting  

Cote G, Alqaisi HA, Sridhar SS, et al.

Kidney and Cancer Outcomes with Standard vs. Kidney Protective Chemotherapy Regimens for First-Line Treatment of Metastatic Urothelial Carcinoma

ASN Annual Meeting 2020 -- Digital Meeting
J Am Soc Nephrol (Oct) 31:10A 2020

BACKGROUND

Cisplatin-based combination chemotherapy regimen is the optimal initial treatment for metastatic urothelial carcinoma, but kidney function eligibility and nephrotoxicity are treatment-limiting for many patients. For patients unfit to receive cisplatin, other options include alternative administration schedules (e.g. split dose cisplatin), carboplatin -based regimens and non-platinum regimens. The aims of this study were to compare cancer outcomes and incidence of acute kidney injury (AKI) during treatment among 3 regimens of chemotherapy.

METHODS

We conducted a single-center retrospective study of patients receiving first- line chemotherapy for metastatic urothelial carcinoma (2005-2019). We compared standard gemcitabine-cisplatin (gem-cis) to: 1) gemcitabine- cisplatin split dose regimen (split) with cisplatin divided over day 1 and 8; and 2) combination of gemcitabine-carboplatin or single-agent gemcitabine (gem/gem-carbo). We used Fine and Gray hazard models accounting for baseline covariates and competing risk of death.

RESULTS

We identified 183 patients (98 gem-cis, 32 split and 53 gem/gem-carbo). Median age was 67 years-old (IQR: 61-73) and 76% were male. Median baseline eGFR was 78 mL/min/1.73m2 (IQR: 66-91) in gem-cis, 64 (48-77) in split, and 45 (33-57) in gem/gem-carbo. Patients receiving split and gem/gem-carbo were older, had worse performance status, and hypertension was more frequent. Split and gem/gem-carbo regimens were associated with higher mortality and progressive disease relative to gem-cis when adjusted for age, baseline eGFR, ECOG, hypertension and diabetes with hazard ratio (HR) of 1.56 (95%CI: 1.04- 2.34; p=0.03) and 2.02 (95%CI: 1.36-3.01; p<0.01) respectively. Median time to progressive disease was 242 (IQR: 137-444), 182 (122-279) and 131 (68 -257) days in gem-cis, split and gem/gem-carbo groups. There was no significant association between regimen type and AKI with HR of 1.32 (95%CI: 0.62-2.81; p=0.47) and 0.98 (95%CI:0.46-2.09; p=0.96) for split and gem/gem- carbo groups versus gem-cis.

CONCLUSION

Kidney protective chemotherapy regimens were associated with increased disease progression and mortality, without a significant difference in AKI. Alternative kidney protective strategies are needed for patients with CKD and urothelial cancer.

c Copyright 2020 -2021 American Society of Nephrology. Reproduced with permission.
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