INTRODUCTION: Regorafenib (Reg) a Tyrosine kinase inhibitor (TKI) recently approved for the treatment of metastatic colorectal cancer patients could be responsible, like others TKIs of potential endocrine side effects, but scanty data are presently available on this specific drug. METHODS: Prospective evaluation of thyroid function, autoimmunity and morphology during treatment with Regorafenib. From November 2015, 17 consecutive patients (7 males and 10 females; mean age 64.2 ± 7.8) with metastatic colorectal cancer with comparable tumor staging, normal thyroid function and no evidence of associated thyroid autoimmunity, were studied before and at monthly intervals after beginning Regorafenib at scheduled dose of 160 mg oral daily according to standard protocols. In all cases FT3, FT4, TSH and thyroid antibodies (TgAb and TPOAb) were measured together with clinical assessment and thyroid ultrasonography up to five months. RESULTS: 8/17 patients (66%) became hypothyroid (TSH 7.9 ± 4.9 mIU/l, range 7.0–18.5) within 30 days of therapy. Interestingly, in 4 of those who developed higher degree of hypothyroidism, we observed highest score of fatigue (G3), the most common general serious adverse event during Reg administration. TPOAb became detectable in 2 (12%) patients 1 month after therapy. Thyroid volume significantly decreased in 9 (52%) patients (from 8.6 ± 2.2 ml before to 4.8 ± 1.6 ml 5 months after Reg, p < 0.01 by paired Student t test), together with the appearance of mild hypoechogenicity and a significant reduction of parenchymal thyroid vascularity (p < 0.05). RESULTS: These data indicate that Reg, similarly to other TKIs inhibitors, may rapidly cause hypothyroidism in about one half of patients, and probably trigger thyroid autoimmunity. An early diagnosis and management of hypothyroidism is therefore mandatory for an effective clinical control of fatigue in most of the cases, in order to prevent unnecessary Reg dose reductions and modifications. Further studies are needed to characterize longer-term effects on thyroid function/autoimmunity and to assess whether hypothyroidism may have a prognostic value as a potential biomarker of clinical response.
Thyroid dysfunction and ultrasonography features in patients with metastatic colorectal cancer treated with Regorafenib. Results from a single centre prospective cohort study.
Pani F
;Orgiano L;Massa E;Boi F;Scartozzi M;Mariotti S.
2016-01-01
Abstract
INTRODUCTION: Regorafenib (Reg) a Tyrosine kinase inhibitor (TKI) recently approved for the treatment of metastatic colorectal cancer patients could be responsible, like others TKIs of potential endocrine side effects, but scanty data are presently available on this specific drug. METHODS: Prospective evaluation of thyroid function, autoimmunity and morphology during treatment with Regorafenib. From November 2015, 17 consecutive patients (7 males and 10 females; mean age 64.2 ± 7.8) with metastatic colorectal cancer with comparable tumor staging, normal thyroid function and no evidence of associated thyroid autoimmunity, were studied before and at monthly intervals after beginning Regorafenib at scheduled dose of 160 mg oral daily according to standard protocols. In all cases FT3, FT4, TSH and thyroid antibodies (TgAb and TPOAb) were measured together with clinical assessment and thyroid ultrasonography up to five months. RESULTS: 8/17 patients (66%) became hypothyroid (TSH 7.9 ± 4.9 mIU/l, range 7.0–18.5) within 30 days of therapy. Interestingly, in 4 of those who developed higher degree of hypothyroidism, we observed highest score of fatigue (G3), the most common general serious adverse event during Reg administration. TPOAb became detectable in 2 (12%) patients 1 month after therapy. Thyroid volume significantly decreased in 9 (52%) patients (from 8.6 ± 2.2 ml before to 4.8 ± 1.6 ml 5 months after Reg, p < 0.01 by paired Student t test), together with the appearance of mild hypoechogenicity and a significant reduction of parenchymal thyroid vascularity (p < 0.05). RESULTS: These data indicate that Reg, similarly to other TKIs inhibitors, may rapidly cause hypothyroidism in about one half of patients, and probably trigger thyroid autoimmunity. An early diagnosis and management of hypothyroidism is therefore mandatory for an effective clinical control of fatigue in most of the cases, in order to prevent unnecessary Reg dose reductions and modifications. Further studies are needed to characterize longer-term effects on thyroid function/autoimmunity and to assess whether hypothyroidism may have a prognostic value as a potential biomarker of clinical response.
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
