Sunitinib in patients with metastatic renal cell carcinoma: Birmingham experience

Abstract

Abstract. Sunitinib is a novel, multi-targeted receptor tyrosine kinase inhibitor, which has demonstrated evidence of improved survival when compared to interferon (IFN)-· in patients with metastatic renal cell carcinoma (RCC). Recently published National Institute for Health and Clinical Excellence guidance recommends sunitinib as a first-line treatment option for patients with advanced and/or metastatic RCC. We assessed the efficacy and toxicity of sunitinib in an unselected group of patients with metastatic RCC, and compared outcomes in clinical practice with published clinical trial results. Between June 2006 and March 2008, 56 patients with metastatic RCC gave informed consent for commencement of sunitinib treatment at our institution. Median age was 61 years (range: 33-78); 68% had clear-cell histology; 86% had undergone prior nephrectomy; and 50% had progressed on IFN-· prior to commencement of sunitinib. Sunitinib was administered orally at a dose of 50 mg once daily, in 6-week cycles consisting of 4 weeks of treatment followed by a 2-week break. All patients were evaluable for toxicity, and 49 for response. The mean dose of sunitinib was 38.15 mg/cycle (range: 25-50); and 402 cycles of sunitinib were delivered. Partial response and stable disease were observed in 41 and 37% of patients, respectively. Median progression-free survival and overall survival were 12.2 and 18.2 months, respectively. The most common adverse events (all grades) were mucositis (79%) and fatigue (75%). Grade 3/4 neutropenia was observed in 13%, and treatmentrelated hypothyroidism in 20%, of patients. Dose-reduction was necessary in 75% of patients, and 32% needed hospital admission for treatment-related toxicities. The results from this study confirm the efficacy of sunitinib in the first-and second-line treatment of an unselected group of patients with metastatic RCC. Compared to published data, there was a higher incidence of treatment-related toxicities and a greater necessity for dose-reductions. Despite the increase in toxicity, these results are encouraging and imply that the clinical trial results seen with sunitinib can be translated into routine clinical practice.

Synergistic Survival: A New Phenomenon Connected to Adverse Events of First-Line Sunitinib Treatment in Advanced Renal Cell Carcinoma

“…The frequency of mucositis and/or stomatitis for sunitinib treatment was reported to be 9% to 79%. 20,26 In our study mucositis and/or stomatitis were associated with significantly better ORR, but not with longer survival.…”

“…1 The orally available drug, sunitinib, is a targeted inhibitor of multiple tyrosine kinases, including VEGF receptors and PDGF. It was approved by the US Food and Drug Administration for the treatment of RCC on January 26,2006. Currently, sunitinib remains the gold standard of care in the treatment of mRCC.…”

Real‐life patterns of use, safety and effectiveness of sunitinib in first‐line therapy of metastatic renal cell carcinoma: the SANTORIN cohort study

“…Owing to the sample size and homogeneity, indirect comparisons with results from the PCT 9,11 and other clinical trials [13][14][15] are more relevant than those derived from other published observational studies. [16][17][18][19][20][21][22][23][24][25] These studies were limited by small sample size, by the concomitant inclusion of mRCC patients treated for second-line therapy, or focus on use and safety or effectiveness only, whereas a global overview is required for relevant drug evaluation. Comparisons between trials and real-life practice are crucial for clinical and policy decision-making, especially here because the populations included in the PCT 9,11 and in SANTORIN were different regarding some important prognostic factors including non-clear cell RCC histology, ECOG status ≥2 and brain metastases that were exclusion criteria for the PCT 9,11 (Table 4).…”

Angiogenesis inhibitor therapies for advanced renal cell carcinoma: Toxicity and treatment patterns in clinical practice from a global medical chart review

“…In the Korean study by Hwang et al (15), 29% of sunitinib patients experienced a dose reduction. In the UK study by Ansari et al (16), 15% of sunitinib patients experienced a dose discontinuation in their first cycle of treatment, and 75% experienced at least one dose reduction. Notably, the number of patients in the current study was several fold higher than the aforementioned observational studies.…”