Adjusted-Dose Combination Therapy May Address Needs of Patients with Urothelial Carcinoma Unable to Tolerate Cisplatin Treatment

Overall survival and progression-free survival did not significantly differ when adjusting the dose of cisplatin in combination with Abraxane (paclitaxel) and gemcitabine in patients with advanced/metastatic urothelial carcinoma, according to a study published in Urologic Oncology.

“To the best of our knowledge, this is the first study to suggest a positive outcome of cisplatin-dose-adjusted chemotherapy for cisplatin-unfit patients with advanced/metastatic (urothelial carcinoma) without significant renal dysfunction,” the study authors wrote. “Dose adjustment of cisplatin might show adequate efficacy and safety profiles without deterioration in renal function.”

Despite improvements in systemic chemotherapy, patients with advanced/metastatic urothelial carcinoma, the most common type of bladder cancer, still have a poor prognosis, according to the study’s introduction. Treatments containing Abraxane are currently used in the second-line setting, although the increased use to immune checkpoint inhibitors may change this treatment landscape. Researchers believe that the efficacy and toxicity of Abraxane, cisplatin and gemcitabine need to be reevaluated as a first-line chemotherapy in the current era of immune checkpoint inhibitors and the clinical environment.

To do so, researchers analyzed data from 50 patients with locally advanced or metastatic urothelial carcinoma who were treated with Abraxane, cisplatin and gemcitabine as first-line therapy between 2008 and 2017. Based on international criteria, 30 of these patients were suitable for treatment with cisplatin whereas 20 patients were not suitable for this specific therapy.

All patients were treated with 80 mg/m2 of Abraxane, 1,000 mg/m2 of gemcitabine on days one and eight and a starting dose of 70 mg/m2 of cisplatin every 28 days. Researchers assessed renal function my measuring 24-hour urinary creatinine clearance before starting a chemotherapy cycle to adjust the cisplatin dose accordingly.

Factors of interest in this study included survival outcomes such as progression-free survival (time during and after treatment without disease progression), overall survival (percentage of patients alive after treatment initiation) and overall response rate (percentage of patients with a partial or complete response to treatment), in addition to side effects. Follow-up was conducted for a median of 15 months.

The median overall survival was 15 months in all patients, 15 months in those suitable for treatment with cisplatin and 13.2 months in patients unsuitable for cisplatin. In addition, the median progression-free survival was 9.8 months for all patients, 10 months for those suitable for cisplatin and 9.3 months for patients unsuitable for cisplatin. Overall survival and progression-free survival did not significantly differ between groups.

The most common severe or life-threatening side effects included low white blood cell/neutrophil counts (78%), low blood platelet counts (56%), anemia and fever with low white blood cell/neutrophil count (16%).

Twenty-four hour urinary creatinine clearance did not significantly differ between groups after one, two or three courses of treatment with Abraxane, cisplatin and gemcitabine.

“Further studies in a larger population may be valuable, even in this (immune checkpoint inhibitor) era, to clarify whether first-line (Abraxane, cisplatin and gemcitabine) with dose adjustment of cisplatin delivers a satisfactory outcome in cisplatin-unfit (urothelial carcinoma) patients.”

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