Endocrine Abstracts

Introduction: To date, only four tyrosine kinase inhibitors (TKIs) have demonstrated beneficial effect on progression free survival in advanced medullary thyroid cancer (MTC; vandetanib and cabozantinib) andradioiodine-refractory differentiated thyroid cancer (RR-DTC; sorafenib and lenvatinib). However, there is still lack of unequivocal proofs of their significant impact on overall survival. Therefore, treatment-related side effects and their potential impact on quality of life has been recently widely discussed.

Aim: We conducted a retrospective analysis to evaluate TKIs toxicity in advanced thyroid cancer. The comparison of particular drugs was not aimed.

Material and Methods: The study group involved 72 patients at mean age at treatment start of 51 ± 14 years. RR-DTC was diagnosed in 32 patients, whereas MTC in 40 subjects. All side effects were evaluated according to CTCAE (Common Terminology Criteria for Adverse Events), V 4.03. The median treatment time was 20.6 months (range: 0.5 months–142.8 months).

Results: In total, 74 treatment courses were assessed: 27 with lenvatinib, 9 with sorafenib, 22 with vandetanib, 9 with cabozantinib, 4 with motesanib, and 3 with axitinib. Treatment-related side effects were present in 97.3% courses. The most common were skin reactions – 68.9% courses, diarrhea – 67.6% courses, hypertension – 59.5% courses, weight loss – 56.8% courses, mucositis – 48.6% courses, abdominal pain– 29.7% courses, fatigue – 29.7% courses, and nausea in 18.9% courses. Skin changes were more frequent in MTC than in RR-DTC patients (P = 0.0128). Similarly, fatigue was reported more commonly by MTC patients than by RR-DTC patients (P = 0.0387). Fatigue also occurred more frequently in patients ≥55 years old at treatment onset comparing to younger ones <55 years. This difference was statistically significant (P = 0.0108). No other significant differences in the frequency of the most common TKI-related side effects were noticed regrading tumor histopathology, age of treatment start, sex, and comorbidities. Due to poor tolerability drug interruption was necessary in 70.3% treatment courses, dose reduction in 62.2% courses, whereas permanent drug withdrawal was required in 25.7% courses.

Conclusions: TKI-related side effects were present in nearly all patients treated due to advanced thyroid cancer. Early diagnosis of adverse effects as well as a supportive management and dose modifications, if necessary, allowed avoiding serious complications and making possible to keep the patient on treatment as long as it was beneficial.

The study was supported by MILESTONE – STRATEGMED 2/26 7398/4/NCBR/2015.