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Sunitinib in metastatic renal cell carcinoma: recommendations for management of noncardiovascular toxicities.

ABSTRACT: The multitargeted tyrosine-kinase inhibitor sunitinib has emerged as one of the standards of care for good- and intermediate-risk metastatic renal cell carcinoma. Although generally associated with acceptable toxicity, sunitinib exhibits a novel and distinct toxicity profile that requires monitoring and management. Fatigue, diarrhea, anorexia, oral changes, hand-foot syndrome and other skin toxicity, thyroid dysfunction, myelotoxicity, and hypertension seem to be the most common and clinically relevant toxicities of sunitinib. Drug dosing and treatment duration are correlated with response to treatment and survival. Treatment recommendations for hypertension have been published but, currently, no standard guidelines exist for the management of noncardiovascular side effects. To discuss the optimal management of noncardiovascular side effects, an international, interdisciplinary panel of experts gathered in November 2009. Existing literature on incidence, severity, and underlying mechanisms of side effects as well as on potential treatment options were carefully reviewed and discussed. On the basis of these proceedings and the thorough review of the existing literature, recommendations were made for the monitoring, prevention, and treatment of the most common noncardiovascular side effects and are summarized in this review. The proactive assessment and consistent and timely management of sunitinib-related side effects are critical to ensure optimal treatment benefit by allowing appropriate drug dosing and prolonged treatment periods.

SUBMITTER: Kollmannsberger C

PROVIDER: S-EPMC3228204 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Sunitinib in metastatic renal cell carcinoma: recommendations for management of noncardiovascular toxicities.

Kollmannsberger Christian C Bjarnason Georg G Burnett Patrick P Creel Patricia P Davis Mellar M Dawson Nancy N Feldman Darren D George Suzanne S Hershman Jerome J Lechner Thomas T Potter Amy A Raymond Eric E Treister Nathaniel N Wood Laura L Wu Shenhong S Bukowski Ronald R

The oncologist 20110413 5

The multitargeted tyrosine-kinase inhibitor sunitinib has emerged as one of the standards of care for good- and intermediate-risk metastatic renal cell carcinoma. Although generally associated with acceptable toxicity, sunitinib exhibits a novel and distinct toxicity profile that requires monitoring and management. Fatigue, diarrhea, anorexia, oral changes, hand-foot syndrome and other skin toxicity, thyroid dysfunction, myelotoxicity, and hypertension seem to be the most common and clinically r ...[more]

PMID: 21490127

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Project description:BackgroundMetastatic renal cell carcinoma (mRCC) patients receiving first-line sunitinib typically survive >2 yr, with chronic treatment sometimes extending to ≥6 yr.ObjectiveTo analyze long-term safety with sunitinib in mRCC patients.Design, setting, and participantsData were pooled from 5739 patients in nine trials, comprising seven phase II studies, a phase III study, and an expanded-access trial in various treatment settings (e.g., cytokine refractory or treatment-naïve).Outcome measurements and statistical analysisInterval and cumulative time-period analyses evaluated the incidence of treatment-related adverse events (TRAEs) for up to 6 yr, in the overall population and in those with long-term (≥2 yr) sunitinib treatment.Results and limitationsAmong long-term patients (n=807), most TRAEs occurred initially in the first year and then decreased in frequency; TRAEs following this pattern included decreased appetite, diarrhea, dysgeusia, dyspepsia, fatigue, hypertension, mucosal inflammation, nausea, and stomatitis. However, hypothyroidism increased by interval analysis from 6% at 0-<6 mo to 42% at 5-<6 yr and by cumulative analysis from 14% at 0-<1 yr to 36% over 6 yr. Grade 3/4 TRAEs in long-term patients peaked during the first year and then steadily decreased. The overall population displayed only minor differences from long-term patients, with no clinically significant differences between grade ≥3 TRAE profiles (<5% difference in incidence rates at all intervals). Limitations included retrospective design, assessment variability, lack of pharmacokinetic data, and absence of baseline characteristics for long-term patients.ConclusionsProlonged sunitinib was not associated with new types or increased severity of TRAEs. Except hypothyroidism, toxicity was not cumulative.Patient summaryMore than 800 mRCC patients received sunitinib for between 2 and 6 yr without experiencing new or more severe treatment-related toxicity. Clinicians may be able to prescribe chronic sunitinib treatment for as long as patients continue to derive clinical benefit, without untoward additional risk.

Project description:Following approval of the oral, multitargeted tyrosine kinase inhibitor sunitinib malate for the treatment of patients with metastatic renal cell carcinoma (mRCC) in Europe and the USA in 2006, the agent has had a substantial impact on the treatment landscape in this setting. Sunitinib is now recommended in international treatment guidelines for the first-line treatment of favourable- or intermediate-risk mRCC and as an alternative option in poor-risk mRCC. In the 6 years since the approval of sunitinib, the range of agents available for the treatment of mRCC has expanded substantially, and this, together with a number of additional therapies in late-stage development, has increased the treatment options available to patients. Results from a phase III trial and a global expanded access study have provided robust data to support the efficacy of sunitinib in mRCC, including in real-world populations. Data also suggest a significant quality of life benefit with sunitinib, with superior patient-reported outcomes observed with this agent compared with interferon-α therapy. Both clinical and real-world study data also support the safety profile of sunitinib; most treatment-associated adverse events are mild to moderate in severity and can be managed effectively with close monitoring and proactive management. Clinical experience with sunitinib has demonstrated that therapy management, involving optimal dosing, maximum treatment duration and prompt and effective adverse event management, supports optimal patient outcomes with sunitinib. In this review we discuss clinical experience with sunitinib in mRCC, with an emphasis on real-world data, and utilize clinical case studies to examine the successful implementation of therapy management strategies for optimal patient outcomes. An increasing body of evidence suggests that side effects associated with sunitinib therapy, including hypertension, hand-foot syndrome and hypothyroidism, may represent effective markers of treatment response, and these will also be discussed.

Dataset Information

Sunitinib in metastatic renal cell carcinoma: recommendations for management of noncardiovascular toxicities.

Publications

Sunitinib in metastatic renal cell carcinoma: recommendations for management of noncardiovascular toxicities.

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