Sunitinib administered on 2/1 schedule in patients with metastatic renal cell carcinoma: The RAINBOW analysis (original) (raw)
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Współczesna Onkologia, 2020
Introduction: Sunitinib is a standard of care first line treatment for patients with metastatic renal cell carcinoma (RCC). Sunitinib standard dose is 50 mg once daily for 4 consecutive weeks followed by 2 weeks' off (4/2 schedule). Long-term and high exposure to this medication lead to severe adverse events (AEs); therefore, this trial was done to find the best schedule which gives the best outcome with minimal toxicity. Materials and methods: Seventy patients were randomly assigned into 2 groups, then received 50 mg/day of sunitinib. Group 1 (40 patients) received sunitinib for 4 consecutive weeks followed by 2 weeks off (4/2 schedule) while 30 patients were admitted to group 2 with 2 weeks on and 1 week off (2/1 schedule). Results: All patients (100%) had significantly higher AEs on schedule 4/2 vs. 73.3% on schedule 2/1 (p = 0.001). Furthermore, the grade 3 AEs on schedule 2/1 were significantly lower than those on schedule 4/2 (26.7% vs. 82.5%) respectively (p = 0.001), such as fatigue, diarrhea, hypertension, hand foot syndrome (HFS) and mucositis. Progression-free survival (PFS) rate was significantly higher in 2/1 schedule (60.9% vs. 38.6%) than in 4/2 schedule (p < 0.008). Multivariate analysis suggested that: age > 60 years, poor International Metastatic RCC Database Consortium (IMDC) risk category, tumor size > 10 cm and treatment schedule (group 1) were poor prognostic factors of PFS. Conclusions: Our study supported the use of 2/1 schedule of sunitinib in patients with metastatic RCC because of lower toxicity profile and better efficacy with improved PFS in comparison to 4/2 schedule.
Cancer, 2012
BACKGROUND: Sunitinib at 50 mg/day on the 4-weeks-on-2-weeks-off schedule is the current approved regimen for advanced/metastatic renal cell carcinoma (mRCC). Escudier et al reported that continuous, once-daily dosing with sunitinib 37.5 mg had a manageable safety profile and significant antitumor activity as second-line mRCC therapy. In this prospective, multicenter, phase II study, we evaluated the activity of continuous once-daily dosing with sunitinib 37.5 mg as first-line mRCC treatment. METHODS: One hundred nineteen treatment-naive patients with measurable mRCC received sunitinib. The primary endpoint was objective response; secondary endpoints included progressionfree survival (PFS), safety, pharmacokinetic measurements, exploration of response biomarkers, and patient reported outcomes (PRO). RESULTS: Objective response rate (ORR) was 35.3%; median response duration was 10.4 months; 36% of patients had stable disease 12 weeks. Median PFS at 1 year was 9 months, and 1-year survival probability was 67.8%. The most common any-grade treatment-related adverse events (AEs) were diarrhea (50%) and hand-foot syndrome (43%); the most common grade 3-4 treatment-related AEs were hand-foot syndrome (13%), neutropenia (11%), and diarrhea (9%). Steady-state pharmacokinetics were reached within 3 weeks, with no disproportionate accumulation of sunitinib or its active metabolite throughout the study. No significant correlations between trough drug, active metabolite, or soluble protein levels and clinical response were observed. PRO was largely maintained, although fatigue appeared to worsen after treatment started, with improvement over time. CONCLUSIONS: Continuous once-daily dosing with sunitinib 37.5 mg was active with a manageable safety profile as first-line mRCC therapy, making this a feasible alternative dosing regimen. Cancer 2012;118:1252-9
Contemporary oncology (Poznań, Poland), 2016
Sunitinib-related side effects may develop as a result of the pharmacokinetic pathway affects the of the drug. Data on mRCC patients were obtained from the hospital archives. Outcomes of patients were evaluated in terms of related prognostic factors, sunitinib adverse events during the treatment, and two different sunitinib dosing schedules. Seventy patients diagnosed with mRCC and treated with sunitinib were analyzed for prognostic factors and survival rates. During the mean follow-up of 33.5 months, 38 (54%) patients were alive and 32 (46%) patients died. The median time of overall survival (OS) and progression-free survival (PFS) was 27 months (12-61) and 19 months (5-45), respectively. In univariate analysis, good prognostic risk group according to the Memorial Sloan-Kettering Cancer Center (MSKCC), hypothyroidism as sunitinib toxicity and patients on sunitinib treatment more than 1 year were favorable prognostic factors for OS. Leukopenia and fatigue as sunitinib toxicity were ...
Cancer Medicine, 2014
Angiogenesis inhibitors have become standard of care for advanced and/or metastatic renal cell carcinoma (RCC), but data on the impact of adverse events (AEs) and treatment modifications associated with these agents are limited. Medical records were abstracted at 10 tertiary oncology centers in Europe for 291 patients ≥18 years old treated with sunitinib as first-line treatment for advanced RCC (no prior systemic treatment for advanced disease). Logistic regression models were estimated to compare dose intensity among patients who did and did not experience AEs during the landmark periods (18, 24, and 30 weeks). Cox proportional hazard models were used to explore the possible relationship of low-dose intensity (defined using thresholds of 0.7, 0.8, and 0.9) and treatment modifications during the landmark periods to survival. 64.4% to 67.9% of patients treated with sunitinib reported at least one AE of any grade, and approximately 10% of patients experienced at least one severe (grade 3 or 4) AE. Patients reporting severe AEs were statistically significantly more likely to have dose intensities below either 0.8 or 0.9. Dose intensity below 0.7 and dose discontinuation during all landmark periods were statistically significantly associated with shorter survival time. This study of advanced RCC patients treated with sunitinib in Europe found a significant relationship between AEs and dose intensity. It also found correlations between dose intensity and shorter survival, and between dose discontinuation and shorter survival. These results confirm the importance of tolerable treatment and maintaining dose intensity.
Journal of Urology, 2014
Purpose-To identify sunitinib alternative schedules (AS) that maintained dose intensity while decreasing adverse events (AEs) in patients with metastatic renal cell cancer (mRCC), and to determine impact of AS on clinical outcomes. Patients and Methods-A retrospective review of patients ≥ 18 yr of age with clear-cell mRCC who received first-line sunitinib between 1/26/06 and 3/1/11 at a major Comprehensive Cancer Center. Subset of patients switched at first intolerable AE from traditional schedule (28 d on, 14 d off; TS) to 14 d on/7 d off schedule or other AS. Control group underwent standard dose reduction. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Predictors of PFS and OS were analyzed using Cox regression. Results-One hundred eighty five patients were included for analysis; 87% were on TS at baseline. During treatment, 53% of patients continued TS and 47% initiated or transitioned to AS. Baseline characteristics were similar. AEs prompting schedule modification included fatigue (64%), hand-foot syndrome (38%) and diarrhea (32%). Median time to AS was 5.6 mo. Median OS was 17.7 mo (95% confidence interval [CI], 10.8-22.2) on TS compared to 33.0 mo (95% CI, 29.3-not estimable) on AS (P < 0.0001). By multivariable analysis; poor ECOG PS, increased LDH, decreased albumin, unfavorable Heng criteria, and TS are associated with decreased OS (P < 0.05).
Japanese Journal of Clinical Oncology, 2011
Objective: Therapy targeted against the vascular endothelial growth factor pathway is a standard of care for patients with metastatic renal cell carcinoma. This study assessed the response rates and toxicity profiles of sunitinib on a continuous once-daily dosing regimen in Turkish patients with metastatic renal cell carcinoma. Methods: Between April 2006 and August 2010, 74 patients with metastatic renal cell carcinoma who received sunitinib on a continuous, once-daily dosing regimen were included. Sunitinib was administered daily at a dose of either 37.5 mg (94% of the patients) or 25 mg (6% of the patients), without interruption, either as a second-line treatment after interferon-a or as a first-line treatment. Response, toxicity, progression-free survival and overall survival were evaluated. Results: Of the 74 patients, 65 (88%) were diagnosed with clear cell renal cell carcinoma. The median treatment duration was 10 months (range, 2 -42 months). The most common treatment-related adverse events were fatigue (75%), stomatitis (51%) and hypertension (50%). The most common Grade 3 or 4 adverse events were anemia (10%) and hand -foot syndrome (7%). Dose reductions were required in 50% of the patients, and early treatment discontinuation was necessary in 16% of the patients. Cardiovascular events were the most common adverse events that resulted in drug discontinuation. The objective response rate and the disease control rate were 30 and 78%, respectively. The median progression-free survival and overall survival were 13 and 25 months, respectively. Conclusions: Continuous, once-daily administration of sunitinib was generally well tolerated in Turkish patients with advanced renal cell carcinoma in a daily practice setting. This study's response rates were comparable to those in previous randomized trials.
Safety and efficacy of sunitinib for metastatic renal-cell carcinoma: an expanded-access trial
The Lancet Oncology, 2009
Background Results from clinical trials have established sunitinib as a standard of care for fi rst-line treatment of advanced or metastatic renal-cell carcinoma (RCC); however, many patients, particularly those with a poorer prognosis, do not meet inclusion criteria and little is known about the activity of sunitinib in these subgroups. The primary objective of this trial was to provide sunitinib on a compassionate-use basis to trial-ineligible patients with RCC from countries where regulatory approval had not been granted. Methods Previously treated and treatment-naive patients at least 18 years of age with metastatic RCC were eligible. All patients received open-label sunitinib 50 mg orally once daily on schedule 4-2 (4 weeks on treatment, 2 weeks off). Safety was assessed regularly, tumour measurements done per local practice, and survival data collected where possible. Analyses were done in the modifi ed intention-to-treat (ITT) population, which consisted of all patients who received at least one dose of sunitinib. This study is registered with ClinicalTrials.gov, NCT00130897. Findings As of December, 2007, 4564 patients were enrolled in 52 countries. 4371 patients were included in the modifi ed ITT population. This population included 321 (7%) patients with brain metastases, 582 (13%) with Eastern Cooperative Oncology Group (ECOG) performance status of 2 or higher, 588 (13%) non-clear-cell RCC, and 1418 (32%) aged 65 years or more. Patients received a median of fi ve treatment cycles (range 1-25). Reasons for discontinuation included lack of effi cacy (n=1168 [27%]) and adverse events (n=362 [8%]). The most common treatment-related adverse events were diarrhoea (n=1936 [44%]) and fatigue (n=1606 [37%]). The most common grade 3-4 adverse events were fatigue (n=344 [8%]) and thrombocytopenia (n=338 [8%]) with incidences of grade 3-4 adverse events similar across subgroups. In 3464 evaluable patients, the objective response rate (ORR) was 17% (n=603), with subgroup ORR as follows: brain metastases (26 of 213 [12%]), ECOG performance status 2 or higher (29 of 319 [9%]), non-clear-cell RCC (48 of 437 [11%]) and age 65 years or more (176 of 1056 [17%]). Median progression-free survival was 10•9 months (95% CI 10•3-11•2) and overall survival was 18•4 months (17•4-19•2). Interpretation In a broad population of patients with metastatic RCC, the safety profi le of sunitinib 50 mg once-daily (initial dose) on schedule 4-2 was manageable and effi cacy results were encouraging, particularly in subgroups associated with poor prognosis who are not usually entered into clinical trials.
BMC cancer, 2018
In patients with metastatic renal cell cancer, based on limited evidence, increased sunitinib exposure is associated with better outcome. The survival and toxicity data of patients receiving individualized dose escalated sunitinib therapy as compared to standard management were analyzed in this study. From July 2013, the data of metastatic renal cell cancer patients with slight progression but still a stable disease according to RECIST 1.1 criteria treated with an escalated dose of sunitinib (first level: 62.5 mg/day in 4/2 or 2 × 2/1 scheme, second level: 75 mg/day in 4/2 or 2 × 2/1 scheme) were collected prospectively. Regarding characteristics, outcome, and toxicity data, an explorative retrospective analysis of the register was carried out, comparing treatments after and before July 1, 2013 in the study (selected patients for escalated dose) and control (standard dose) groups, respectively. The study involved 103 patients receiving sunitinib therapy with a median overall and pro...