Long-term Safety of Sunitinib in Metastatic Renal Cell Carcinoma.
Eur Urol
; 69(2): 345-51, 2016 Feb.
Article
en En
| MEDLINE
| ID: mdl-26215605
ABSTRACT
BACKGROUND:
Metastatic renal cell carcinoma (mRCC) patients receiving first-line sunitinib typically survive >2 yr, with chronic treatment sometimes extending to ≥6 yr.OBJECTIVE:
To analyze long-term safety with sunitinib in mRCC patients. DESIGN, SETTING, ANDPARTICIPANTS:
Data 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 STATISTICALANALYSIS:
Interval 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 ANDLIMITATIONS:
Among 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.CONCLUSIONS:
Prolonged sunitinib was not associated with new types or increased severity of TRAEs. Except hypothyroidism, toxicity was not cumulative. PATIENTSUMMARY:
More 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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Pirroles
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Carcinoma de Células Renales
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Indoles
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Neoplasias Renales
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Antineoplásicos
Límite:
Female
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Humans
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Male
Idioma:
En
Revista:
Eur Urol
Año:
2016
Tipo del documento:
Article