90IN - Endocrine toxicity

Date 27 September 2014
Event ESMO 2014
Session Targeting precision medicine toxicity
Topics Complications/Toxicities of Treatment
Supportive Measures
Presenter Fausto Roila
Citation Annals of Oncology (2014) 25 (suppl_4): iv33-iv34. 10.1093/annonc/mdu310
Authors F. Roila
  • Oncologia Medica, Azienda Ospedaliera Sta Maria, 05100 - Terni/IT




Different endocrine toxicities induced by targeted therapies have been reported; the most important will be described. Hypothyroidism is generally induced by the multikinase inhibitors sunitinib, sorafenib, axitinib, pazopanib, regorafenib and cabozantinib. Thyroid dysfunction occurs in 20–50% of the patients (pts) receiving these drugs. Despite this, symptoms of hypothyroidism, such as fatigue, weakness, constipation, depression, and cold intolerance may be incorrectly attributed to the primary disease or to the antineoplastic agent. This can have important conseguences for cancer patient management; in fact, the symptoms can lead to dose reductions of potentially life-saving therapies, to alter kinetics and clearance of medictions, with undesirable side effects and to a negative impact on the patient's quality of life. The hypothiroidism can be classified into 2 types: recurrent and de novo hypothyroidism. The former, described with imatinib, sorafenib and motesanib, is characterized by increased TSH levels within 2 weeks of starting therapy and occurs in thyroidectomized pts with known hypothyroidism controlled with stable dose of levothyroxine. The second, described with sunitinib, sorafenib, and axitinib, is the de novo hypothyroidism, diagnosed in pts with regular thyroid function before the start of therapies. Therefore, in pts starting multikinase inhibitors it is recommended to monitor TSH and T4 at baseline and every 4 weeks. Central hypogonadism has recently been reported in 80–100% male pts receiving crizotinib. It occurs within 2–3 weeks of crizotinib initiation, is diagnosed by reduction in testosterone, FSH and LH levels and is reversible with treatment interruption. In pts submitted to crizotinib it is important to monitor symptoms of hypogonadism such as erectile dysfunction, fatigue, loss of muscle mass, to check testosterone levels, and, if indicated, to administer testosterone replacement. Finally different immune-related endocrinopaties have been described with ipilimumab. Therefore evaluation is suggested before and during treatment of the pituitary, thyroid, adrenal, and gonadal status. Endocrine toxicities have a negative impact on the patient's quality of life; therefore, they should be known and adequately treated.


The author has declared no conflicts of interest.