Grade 3 and/or 4 toxicities are an indication for treatment discontinuation; however, lower-grade side effects may also lead to treatment withdrawal, especially when they appear in clusters and persist for a long time. Apart from implementation of supportive measures,30 as cited in our methodology, we applied drug discontinuation and dose reduction to alleviate symptoms in patients with toxicities.23Recently, a schedule change from 4 weeks on/2 weeks off during treatment with sunitinib to 2 weeks on/1 week off has resulted in significantly fewer events of hand-foot syndrome and fatigue.31 This alternative dosing led to fewer grade 3/4 adverse events without compromising drug efficacy, and so far appears superior to dose reduction.32 Adverse events with one TKI agent do not preclude the use of another drug in this category;33 improvement of hematological toxicity was observed in two patients when treatment was switched from sunitinib to sorafenib.
Previous reports advocate the use of tumor markers (thyroglobulin and calcitonin) as surrogate markers34 for follow-up in treated patients, along with CT and MRI. Although our patient population was small, we also observed a non-significant trend for reduction of tumor markers with treatment. An elevation in TSH was observed, and thyroxine was increased in three patients. In athyreotic patients, increases in TSH with TKI treatment have been previously documented in 17%–33% of patients, depending on the drug used.30 TKIs induce hypothyroidism, probably associated with poor absorption of thyroxine along the gastrointestinal tract as a consequence of diarrhea, thyroid hormone metabolism, or reduction of TSH clearance.35
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This was a retrospective study and included a relatively small number of patients. However, the fact that these data reflect the experience of a single center using standard therapeutic criteria and treating patients from a specific region could counterbalance some of the limitations. Further, since data related to specific populations are not widely available, the present series adds valuable information related to treatment with TKIs. Small groups of patients are common in this research area, as seen in other recently published studies that refer to similar numbers of patients36–38 and contain mixed DTC and MTC populations.16,39,40
CONCLUSION
TKIs represent a valuable therapeutic option in patients with thyroid cancer. However, these agents should be used with caution and under expert supervision because of their adverse events. Younger patients tolerate treatment better. In patients who continue therapy, adverse events may improve over time and become more tolerable. Apart from thorough education of selected patients, topical therapies, dose reduction of the administered TKI, temporary treatment interruption, and/or permanent discontinuation in severe cases may be considered in those not able to continue long-term treatment. As toxicities impact negatively on patients’ quality of life and often restrict their everyday activities, candidate patients must be meticulous selected and close follow-up should be applied.
Disclosure
The authors report no conflicts of interest in this work. The authors alone are responsible for the content and writing of the paper.
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Source: OncoTragets and Therapy
Originally published on September 3, 2015.
