Clinical Experience of Escalated Sunitinib Dose in Select Patients With Metastatic Renal Cell Carcinoma.

Objective: Sunitinib is approved multinationally for the first-line treatment of metastatic renal cell carcinoma (mRCC). After mRCC progressed in patients, we escalated the sunitinib dose in selected patients and then retrospectively evaluated the efficacy and safety of dose-escalated sunitinib in these selected patients.

Methods: From January 2010 to January 2016, 288 patients with mRCC received sunitinib as first-line treatment. Treatment continued until radiologic progression occurred. When the disease progressed, 34 patients with mRCC who had mild or moderate adverse events and missed free second-line target therapy trials were escalated to sunitinib 50 mg once daily continuously. Dose-escalated treatment continued until the disease progressed again, the patient was unable to tolerate sunitinib, or the patient was willing to quit the sunitinib treatment.

Results: All 34 patients (median age, 55 years [range, 28-67 years]; 28 [82.4%] males; 6 [17.6%] females) with confirmed metastatic clear-cell RCC, received an escalated dose of sunitinib and were evaluated for toxicity and response. During treatment at the regular sunitinib dosage, 9 (26.5%) patients achieved partial response and 25 (73.5%) patients had a stable disease condition. With dose-escalated sunitinib, 2 (5.9%) patients achieved partial response, 27 (79.4%) patients had stable disease, and the disease still progressed in 5 (14.7%) patients. Tumor size was reduced in 10 (38.2%) patients. Median progression-free survival was 11.2 months (95% confidence interval [CI], 5.2-17.2 months) with the regular dose of sunitinib. During dose-escalated sunitinib treatment, the median progression-free survival was 4.1 months (95% CI, 2.3-5.9 months). Median overall survival was 25.0 months from the initiation of sunitinib treatment (95% CI, 16.0-34.0 months). During dose escalation, grade 3 adverse events consisted of hand-foot syndrome, fatigue, mucositis, and diarrhea. All grade 3 adverse events were relieved by supporting and symptomatic treatment. No grade 4 adverse events occurred.

Conclusion: Sunitinib was efficacious in the treatment of mRCC. For patients who tolerated sunitinib well, the dosage could be cautiously increased to gain better treatment benefit.