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Medline ® Abstract for Reference 9

of '进展期(晚期)或转移性肾透明细胞癌的抗血管生成和分子靶向治疗'

Outcomes in patients with metastatic renal cell cancer treated with individualized sunitinib therapy: correlation with dynamic microbubble ultrasound data and review of the literature.
Bjarnason GA, Khalil B, Hudson JM, Williams R, Milot LM, Atri M, Kiss A, Burns PN
Urol Oncol. 2014 May;32(4):480-7. Epub 2013 Dec 8.
BACKGROUND: Increased sunitinib exposure (area under the curve) is associated with better outcome in metastatic renal cell cancer. Recommendations for dose modification do not take this into account. A treatment strategy, based on individual patient toxicity, was developed to maximize dose and minimize time without therapy for patients who could not tolerate the standard sunitinib schedule of 50mg given for 28 days with a 14-day break (50mg, 28/14).
METHODS: A single-center retrospective review was conducted on patients with metastatic renal cell cancer treated from October 2005 to March 2010. Dose/schedule modifications (DSM) were done to keep toxicity (hematological, fatigue, skin, and gastrointestinal) at≤grade 2. DSM-1 was 50mg, 14 days on/7 days off with individualized increases in days on treatment. DSM-2 was 50mg, 7 days on/7 days off with individualized increase in days on treatment. DSM-3 was 37.5mg with individualized 7-day breaks. DSM-4 was 25mg with individualized 7-day breaks. Multivariable analysis was performed for outcome as a function of patient and treatment variables.
RESULTS: Overall, 172 patients were included in the analysis. Most patients had clear cell histology (79.1%) with sunitinib given as a first-line therapy in 59%. The DSM-1 and 2 and DSM-3 and 4 groups had a progression-free survival (PFS) (10.9-11.9 mo) and overall survival (OS) (23.4-24.5 mo) that was significantly better than the PFS (5.3 mo; P<0.001) and OS (14.4 mo; P = 0.03 and 0.003) for the standard schedule (50mg, 28/14). DCE-US in a subset of patients showed that maximum antiangiogenic activity was achieved after 14 days on therapy.
CONCLUSIONS: Individualized sunitinib scheduling based on toxicity may improve PFS and OS. This hypothesis is supported by several other respective data that are reviewed. A confirmatory prospective trial is ongoing.
Division of Medical Oncology, Sunnybrook Odette Cancer Centre, Toronto, Canada. Electronic address: georg.bjarnason@sunnybrook.ca.