The tyrosine kinase inhibitors (TKIs) sunitinib target the vascular
endothelial growth factor (VEGF) pathway, is the first targeted
agent to be approved for the first line treatment of metastatic RCC.
The objective of this study was to investigate the efficacy and safety
of Sunitinib in treating metastatic clear-cell RCC and to confirm if
hypertension is an effective predictive factor.
A total of 36 patients with metastatic RCC were enrolled
between June 2008 and Dec 2010.Among them 29 cases were
first line therapy and 7 cases were in progression on first-line
cytokine or sorafinib therapy. The pathology of all patients was
confirmed predominant in clear cell type. Sunitinib monotherapy
was administered in repeated 6-week cycles of daily oral
therapy for 4 weeks, followed by 2 weeks off in 34 patients; and 3
patients were administered with 37.5 mg Qd continuously until
disease progression or unacceptable toxicities occurred. Overall
response rate and safety were evaluated. Hypertension is defined
as a repeatedly (at least twice) elevated BP, with a systolic
pressure >140 mmHg and/or a diastolic pressure >90 mmHg.
We divided patients into Group A and Group B according to
blood pressure level.
The median follow-up was 15 months (10 cycles), range
1.5-30 months (1 - 20 cycles). 29.4% (10/34) of the patients
achieved partial responses (PR); 67.6% (23/34) of the patients
demonstrated stable disease (SD) lasting ≥2 cycles. 17 (50%)
patients developed progressive disease (PD) during follow-up.
The median PFS is 15 (range, 3-28.5) months. A total of 9 patients
died; the overall survival has not been reached; the median survival
time of the deceased patients was 13 (7-24) months. The most
common adverse events (AEs) were hand-foot syndrome (77.8%),
thrombocytopenia (75%), hypertension (61.1%) and diarrhea
(46%). Most AEs were reversible by treatment interruption. 22
(61.1%) patients developed hypertension; hypertension was
associated with a long time to disease progression and long overall
survival (P=.004, .000, respectively).
The results of this study demonstrate the efficacy and
manageable adverse event profile of Sunitinib as a single agent in
first- or second-line therapy for patients with metastatic clear cell
RCC. Further, Sunitinib-associated hypertension may be a strong
predictive marker for treatment efficacy in metastatic RCC.