Evaluation of Gemcitabine and Carboplatin Dosing in Patients With Cisplatin-Ineligible Metastatic Urothelial Carcinoma

Background: The National Comprehensive Cancer Network Bladder Cancer Guidelines recommend carboplatin and gemcitabine first-line treatment in patients with cisplatin-ineligible, metastatic urothelial cancer (mUC) -- a Category 1 recommendation. For these patients, the median overall survival is 9.3 months. While carboplatin is purported to offer a more tolerable side-effect profile, many patients still require dose-reductions, dose-delays, and hospitalizations. Given the inability for mUC patients to tolerate this palliative regimen, we aim to determine whether initiating therapy with a lower dose regimen is justified.

Methods: A single-institution retrospective analysis was conducted to review eligible patients treated with carboplatin plus gemcitabine from May 2014 through October 2022. Data collected via manual chart review included patient baseline characteristics, chemotherapy doses, reductions, delays, toxicities, and effectiveness.

Results: Forty-three patients met inclusion criteria. Nineteen patients (44%) required ≥ 1 dose reduction during therapy. Twenty-six patients (60%) started with a full-dose regimen, and 14 (54%) of those patients required a dose reduction during treatment. Seventeen patients (40%) started with a reduced-dose regimen, and 5 (29%) of those patients required a dose reduction during treatment. No patients received the anticipated 6 cycles at full dose, but 14% completed 6 cycles with dose reductions. One patient (2%) was able to tolerate >80% relative dose intensity of both carboplatin and gemcitabine.

Conclusions: Cisplatin-ineligible mUC patients were unable to tolerate full-dose carboplatin and gemcitabine. As this is a palliative regimen, it would be pertinent to consider starting therapy at a reduced dose to minimize treatment interruptions, dose omissions and side effects.