Clinical Effect of Dose Escalation After Disease Progression in Patients With Metastatic Renal Cell Carcinoma

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Patients taking tyrosine kinase inhibitors (TKIs) for metastatic renal cell carcinoma might benefit from dose escalation at the occurrence of progressive disease (PD). The data from patients who underwent TKI dose escalation at PD were retrospectively reviewed. The median duration of therapy after PD (10.1 months) was longer than that before PD (6.8 months), suggesting an antitumor effect with TKI dose escalation at PD.


Given the variability in drug levels with tyrosine kinase inhibitors (TKIs) in patients with metastatic renal cell carcinoma (mRCC), dose escalation at the occurrence of progressive disease (PD) might have antitumor effects.

Patients and Methods:

The data from patients with mRCC who were treated at the Cleveland Clinic with TKIs and received a dose escalation after PD in accordance with Response Evaluation Criteria In Solid Tumors (RECIST), version 1.1, were retrospectively reviewed. Patient- and disease-related data were collected and summarized as frequency counts and percentages or medians and ranges. The Kaplan-Meier method was used to summarize the treatment duration for the escalated doses.


Twenty-two patients were identified. Most patients (82%) were men; the median age at diagnosis was 58 years (range, 40-71 years). The most common histologic type was clear cell (73%). Axitinib was the most frequently escalated agent after PD (17 patients), followed by sunitinib (3 patients), and pazopanib (2 patients). Before PD, the median treatment duration was 6.8 months (range, 1.6-50.6 months). Of the 18 patients with evaluable tumor measurements after dose escalation, 14 (78%) had a decrease in tumor burden. The median decrease in tumor burden after dose escalation was 14% (range, 2%-58%); 4 patients (22%) had decreases ≥10%, 2 (11%) ≥20%, and 4 (22%) >30% (RECIST partial response). At the last follow-up examination, 5 patients (23%) continued to be treated at escalated doses. The median duration of escalated therapy was estimated at 10.1 months (range, 0.6 to 37.9 months).


Dose escalation of TKIs after PD for select patients with mRCC can lead to a reduction in tumor burden and extend the duration of therapy.

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