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Predictive factors for severe toxicity of sunitinib in unselected patients with advanced renal cell cancer.

van der Veldt AA, Boven E, Helgason HH, van Wouwe M, Berkhof J, de Gast G, Mallo H, Tillier CN, van den Eertwegh AJ, Haanen JB - Br. J. Cancer (2008)

Bottom Line: Importantly, 47 patients (57%) needed a dose reduction, 35 (43%) because of treatment-related adverse events, 10 (12%) because of continuous dosing, and two because of both.Stomatitis, fatigue, hand-foot syndrome and a combination of grade 1-2 adverse events were the most frequent reasons for dose reduction.In 40 patients (49%), there was severe toxicity, defined as dose reduction or permanent discontinuation, which was highly correlated with low body surface area, high age and female gender.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology, VU University medical center, Amsterdam, The Netherlands.

ABSTRACT
Sunitinib has been registered for the treatment of advanced renal cell cancer (RCC). As patient inclusion was highly selective in previous studies, experience with sunitinib in general oncological practice remains to be reported. We determined the efficacy and safety of sunitinib in patients with advanced RCC included in an expanded access programme. ECOG performance status >1, histology other than clear cell and presence of brain metastases were no exclusion criteria. Eighty-two patients were treated: 23% reached a partial response, 50% had stable disease, 20% progressed and six patients were not evaluable. Median progression-free survival (PFS) was 9 months and median overall survival (OS) was 15 months. Importantly, 47 patients (57%) needed a dose reduction, 35 (43%) because of treatment-related adverse events, 10 (12%) because of continuous dosing, and two because of both. Stomatitis, fatigue, hand-foot syndrome and a combination of grade 1-2 adverse events were the most frequent reasons for dose reduction. In 40 patients (49%), there was severe toxicity, defined as dose reduction or permanent discontinuation, which was highly correlated with low body surface area, high age and female gender. On the basis of age and gender, a model was developed that could predict the probability of severe toxicity.

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Related in: MedlinePlus

Probability of severe toxicity from sunitinib (50 mg per day 4 weeks on and 2 weeks off) in patients with advanced RCC based on the following model: Probability of severe toxicity in male patients=exp (−3.986+0.059*age)/(exp (−3.986+0.059*age)+1) Probability of severe toxicity in female patients=exp (−2.750+0.059*age)/(exp (−2.750+0.059*age)+1) Grey lines represent confidence intervals.
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fig2: Probability of severe toxicity from sunitinib (50 mg per day 4 weeks on and 2 weeks off) in patients with advanced RCC based on the following model: Probability of severe toxicity in male patients=exp (−3.986+0.059*age)/(exp (−3.986+0.059*age)+1) Probability of severe toxicity in female patients=exp (−2.750+0.059*age)/(exp (−2.750+0.059*age)+1) Grey lines represent confidence intervals.

Mentions: Female gender, high age, low BSA and to a lesser extent also high LDH were significantly related with severe toxicity (univariate logistic regression; P=0.006, P=0.006, P=0.005 and P=0.035, respectively). There was no significant relation between severe toxicity and the separate prognostic risk groups according to the MSKCC criteria (Motzer et al, 2002) as well as the criteria of Choueiri et al (2007). In multivariate logistic regression of gender, age, BSA and LDH, the latter two variables appeared to be of no additional significance in the prediction of severe toxicity. In multivariate logistic regression, gender and age had a significant effect (P=0.018 and P=0.024, respectively) and the combination of these two variables was highly predictive for severe toxicity (P=0.001). On the basis of gender and age, a model was developed to predict the probability of severe toxicity in male patients and female patients (Figure 2).


Predictive factors for severe toxicity of sunitinib in unselected patients with advanced renal cell cancer.

van der Veldt AA, Boven E, Helgason HH, van Wouwe M, Berkhof J, de Gast G, Mallo H, Tillier CN, van den Eertwegh AJ, Haanen JB - Br. J. Cancer (2008)

Probability of severe toxicity from sunitinib (50 mg per day 4 weeks on and 2 weeks off) in patients with advanced RCC based on the following model: Probability of severe toxicity in male patients=exp (−3.986+0.059*age)/(exp (−3.986+0.059*age)+1) Probability of severe toxicity in female patients=exp (−2.750+0.059*age)/(exp (−2.750+0.059*age)+1) Grey lines represent confidence intervals.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2480961&req=5

fig2: Probability of severe toxicity from sunitinib (50 mg per day 4 weeks on and 2 weeks off) in patients with advanced RCC based on the following model: Probability of severe toxicity in male patients=exp (−3.986+0.059*age)/(exp (−3.986+0.059*age)+1) Probability of severe toxicity in female patients=exp (−2.750+0.059*age)/(exp (−2.750+0.059*age)+1) Grey lines represent confidence intervals.
Mentions: Female gender, high age, low BSA and to a lesser extent also high LDH were significantly related with severe toxicity (univariate logistic regression; P=0.006, P=0.006, P=0.005 and P=0.035, respectively). There was no significant relation between severe toxicity and the separate prognostic risk groups according to the MSKCC criteria (Motzer et al, 2002) as well as the criteria of Choueiri et al (2007). In multivariate logistic regression of gender, age, BSA and LDH, the latter two variables appeared to be of no additional significance in the prediction of severe toxicity. In multivariate logistic regression, gender and age had a significant effect (P=0.018 and P=0.024, respectively) and the combination of these two variables was highly predictive for severe toxicity (P=0.001). On the basis of gender and age, a model was developed to predict the probability of severe toxicity in male patients and female patients (Figure 2).

Bottom Line: Importantly, 47 patients (57%) needed a dose reduction, 35 (43%) because of treatment-related adverse events, 10 (12%) because of continuous dosing, and two because of both.Stomatitis, fatigue, hand-foot syndrome and a combination of grade 1-2 adverse events were the most frequent reasons for dose reduction.In 40 patients (49%), there was severe toxicity, defined as dose reduction or permanent discontinuation, which was highly correlated with low body surface area, high age and female gender.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology, VU University medical center, Amsterdam, The Netherlands.

ABSTRACT
Sunitinib has been registered for the treatment of advanced renal cell cancer (RCC). As patient inclusion was highly selective in previous studies, experience with sunitinib in general oncological practice remains to be reported. We determined the efficacy and safety of sunitinib in patients with advanced RCC included in an expanded access programme. ECOG performance status >1, histology other than clear cell and presence of brain metastases were no exclusion criteria. Eighty-two patients were treated: 23% reached a partial response, 50% had stable disease, 20% progressed and six patients were not evaluable. Median progression-free survival (PFS) was 9 months and median overall survival (OS) was 15 months. Importantly, 47 patients (57%) needed a dose reduction, 35 (43%) because of treatment-related adverse events, 10 (12%) because of continuous dosing, and two because of both. Stomatitis, fatigue, hand-foot syndrome and a combination of grade 1-2 adverse events were the most frequent reasons for dose reduction. In 40 patients (49%), there was severe toxicity, defined as dose reduction or permanent discontinuation, which was highly correlated with low body surface area, high age and female gender. On the basis of age and gender, a model was developed that could predict the probability of severe toxicity.

Show MeSH
Related in: MedlinePlus