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Clinical Cancer Research : An Official... Jul 2023To evaluate the efficacy and safety of dabrafenib-trametinib-131I for the treatment of radioactive iodine refractory metastatic differentiated thyroid cancer (DTC) with...
PURPOSE
To evaluate the efficacy and safety of dabrafenib-trametinib-131I for the treatment of radioactive iodine refractory metastatic differentiated thyroid cancer (DTC) with a BRAF p.V600E mutation.
PATIENTS AND METHODS
A prospective phase II trial including patients with RECIST progression within 18 months and no lesion > 3 cm. Following a baseline recombinant human (rh)TSH-stimulated diagnostic whole-body scan (dc1-WBS), dabrafenib and trametinib were given for 42 days. A second rhTSH-stimulated dc WBS (dc2-WBS) was done at day 28 and 131I (5.5 GBq-150 mCi after rhTSH) was administered at day 35. Primary endpoint was the 6-month RECIST objective response rate. In case of partial response (PR) at 6 or 12 months, a second treatment course could be given. Among 24 enrolled patients, 21 were evaluable at 6 months.
RESULTS
Abnormal 131I uptake was present on 5%, 65%, and 95% of the dc1-WBS, dc2-WBS, and post-therapy scans, respectively. At 6 months, PR was achieved in 38%, stable disease in 52%, and progressive disease (PD) in 10%. Ten patients received a second treatment course: one complete response and 6 PRs were observed at 6 months. The median progression-free survival (PFS) was not reached. The 12- and 24-month PFS were 82% and 68%, respectively. One death due to PD occurred at 24 months. Adverse events (AE) occurred in 96% of the patients, with 10 grade 3-4 AEs in 7 patients.
CONCLUSIONS
Dabrafenib-trametinib is effective in BRAF p.V600E-mutated DTC patients for restoring 131I uptake with PR observed 6 months after 131I administration in 38% of the patients.
Topics: Humans; Thyroid Neoplasms; Iodine Radioisotopes; Proto-Oncogene Proteins B-raf; Thyrotropin Alfa; Prospective Studies; Pyridones; Pyrimidinones; Oximes; Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Mutation
PubMed: 37074727
DOI: 10.1158/1078-0432.CCR-23-0046 -
Advances in Therapy Sep 2021Real-world evidence of the safety and effectiveness of recombinant human thyroid-stimulating hormone (rhTSH; thyrotropin alfa) in Japanese patients is lacking.
INTRODUCTION
Real-world evidence of the safety and effectiveness of recombinant human thyroid-stimulating hormone (rhTSH; thyrotropin alfa) in Japanese patients is lacking.
METHODS
This was a post-marketing surveillance study that included all Japanese patients who received thyrotropin alfa, either as a supporting diagnostic from January 2009 to December 2016, or as adjunctive treatment for ablation from May 2012 to October 2018. Information was collected on patient demographics, thyroid cancer characteristics, adverse drug reactions (ADRs), scintigraphy, serum thyroglobulin (Tg) testing, and hypothyroidism symptoms.
RESULTS
A total of 9268 patients were included in the safety analysis and 9031 in the effectiveness analysis. In the safety analysis set, 3444 patients received thyrotropin alfa as a diagnostic and 5822 received it as treatment. ADRs occurred in 7.1% (n = 660) of patients, including 9.4% (n = 324) of patients who received thyrotropin alfa as a diagnostic and 5.8% (n = 336) of patients who received it as treatment. Nausea was the most common ADR (4.0% of overall safety population). Among patients who received thyrotropin alfa as a diagnostic (n = 1835), the Tg test was positive in 53.6% after the second dose. The scintigram was rated as "readable" in 3023 of the 3054 patients included in this analysis (99.0%). Of the 765 patients who were included in the assessment of response to ablation at 6 months to 1 year after the procedure, 621 (81.2%) were considered to have had "treatment success". There were no significant differences in the proportions of patients who had hypothyroidism symptoms before the first and after the second dose of thyrotropin alfa.
CONCLUSION
In this large post-marketing surveillance study, thyrotropin alfa was well tolerated and showed effectiveness that was comparable to that observed in randomised, controlled trials.
Topics: Humans; Iodine Radioisotopes; Japan; Product Surveillance, Postmarketing; Recombinant Proteins; Thyroglobulin; Thyroid Neoplasms; Thyrotropin; Thyrotropin Alfa
PubMed: 34386895
DOI: 10.1007/s12325-021-01866-9 -
Contact in Context 2023Thyrotropin alfa is a heterodimeric glycoprotein containing human thyroid stimulating hormone (TSH). It is used as an adjunctive diagnostic tool for serum thyroglobulin...
Thyrotropin alfa is a heterodimeric glycoprotein containing human thyroid stimulating hormone (TSH). It is used as an adjunctive diagnostic tool for serum thyroglobulin (Tg) testing with or without radioiodine imaging in the follow-up of patients with well-differentiated thyroid cancer who have previously undergone thyroidectomy. Inter-lot variability in the Fourier transform near-infrared spectra of 30 samples obtained from four separate lots of Thyrogen was detected in the Drug Quality Study (DQS). The vials fell into two distinct groups (r = 0.90, r= 0.98, =0.02). In addition, one vial of the 30 (3%) appeared 4.7 multidimensional SDs from all of the other vials, suggesting that it also represents a different material.
PubMed: 37396298
DOI: 10.6084/m9.figshare.23524530 -
The New England Journal of Medicine May 2012It is not known whether low-dose radioiodine (1.1 GBq [30 mCi]) is as effective as high-dose radioiodine (3.7 GBq [100 mCi]) for treating patients with differentiated... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
It is not known whether low-dose radioiodine (1.1 GBq [30 mCi]) is as effective as high-dose radioiodine (3.7 GBq [100 mCi]) for treating patients with differentiated thyroid cancer or whether the effects of radioiodine (especially at a low dose) are influenced by using either recombinant human thyrotropin (thyrotropin alfa) or thyroid hormone withdrawal.
METHODS
At 29 centers in the United Kingdom, we conducted a randomized noninferiority trial comparing low-dose and high-dose radioiodine, each in combination with either thyrotropin alfa or thyroid hormone withdrawal before ablation. Patients (age range, 16 to 80 years) had tumor stage T1 to T3, with possible spread to nearby lymph nodes but without metastasis. End points were the rate of success of ablation at 6 to 9 months, adverse events, quality of life, and length of hospital stay.
RESULTS
A total of 438 patients underwent randomization; data could be analyzed for 421. Ablation success rates were 85.0% in the group receiving low-dose radioiodine versus 88.9% in the group receiving the high dose and 87.1% in the thyrotropin alfa group versus 86.7% in the group undergoing thyroid hormone withdrawal. All 95% confidence intervals for the differences were within ±10 percentage points, indicating noninferiority. Similar results were found for low-dose radioiodine plus thyrotropin alfa (84.3%) versus high-dose radioiodine plus thyroid hormone withdrawal (87.6%) or high-dose radioiodine plus thyrotropin alfa (90.2%). More patients in the high-dose group than in the low-dose group were hospitalized for at least 3 days (36.3% vs. 13.0%, P<0.001). The proportions of patients with adverse events were 21% in the low-dose group versus 33% in the high-dose group (P=0.007) and 23% in the thyrotropin alfa group versus 30% in the group undergoing thyroid hormone withdrawal (P=0.11).
CONCLUSIONS
Low-dose radioiodine plus thyrotropin alfa was as effective as high-dose radioiodine, with a lower rate of adverse events. (Funded by Cancer Research UK; ClinicalTrials.gov number, NCT00415233.).
Topics: Ablation Techniques; Adolescent; Adult; Aged; Aged, 80 and over; Combined Modality Therapy; Female; Follow-Up Studies; Humans; Hypothyroidism; Iodine Radioisotopes; Length of Stay; Male; Middle Aged; Quality of Life; Radiotherapy Dosage; Thyroid Hormones; Thyroid Neoplasms; Thyroidectomy; Thyrotropin Alfa; Treatment Outcome; Young Adult
PubMed: 22551128
DOI: 10.1056/NEJMoa1109589 -
Recombinant human thyrotropin (rhTSH)-aided radioiodine treatment for non-toxic multinodular goitre.The Cochrane Database of Systematic... Dec 2021Multinodular goitre is common in women. Treatments for non-toxic multinodular goitre include surgery, levothyroxine suppressive therapy, and radioiodine. Radioiodine... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Multinodular goitre is common in women. Treatments for non-toxic multinodular goitre include surgery, levothyroxine suppressive therapy, and radioiodine. Radioiodine therapy is the only non-surgical alternative for non-toxic multinodular goitre. However, a high amount of radioiodine is needed to enable the thyroid nodules to adequately take up the radioiodine, because the multinodular goitre takes up a low amount of iodine. Recombinant human thyrotropin (rhTSH) has been used to increase radioiodine uptake and reduce thyroid volume of the multinodular goitre. Whether the improved reduction of the goitre resulting from rhTSH-stimulated radioiodine therapy is beneficial to the person remains controversial.
OBJECTIVES
To assess the effects of recombinant human thyrotropin-aided radioiodine treatment for non-toxic multinodular goitre.
SEARCH METHODS
We searched the CENTRAL, MEDLINE, Scopus as well as ICTRP Search Portal and ClinicalTrials.gov. The date of the last search of all databases was 18 December 2020.
SELECTION CRITERIA
We included randomised controlled clinical trials (RCTs) comparing the effects of rhTSH-aided radioiodine treatment compared with radioiodine alone for non-toxic multinodular goitre, with at least 12 months of follow-up.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened titles and abstracts for relevance. Screening for inclusion, data extraction, and risk of bias assessment were carried out by one review author and checked by a second. Our main outcomes were health-related quality of life (QoL), hypothyroidism, adverse events, thyroid volume, all-cause mortality, and costs. We used a random-effects model to perform meta-analyses, and calculated risk ratios (RRs) for dichotomous outcomes, and mean differences (MDs) for continuous outcomes, using 95% confidence intervals (CIs) for effect estimates. We evaluated the certainty of the evidence using the GRADE approach.
MAIN RESULTS
We included six RCTs. A total of 197 participants were allocated to rhTSh-aided radioiodine therapy, and 124 participants were allocated to radioiodine. A single dose of radioiodine was administered 24 hours after the intramuscular injection of a single dose of rhTSH. The duration of follow-up ranged between 12 and 36 months. Low-certainty evidence from one study, with 85 participants, showed uncertain effects for QoL for either intervention. RhTSH-aided radioiodine increased hypothyroidism compared with radioiodine alone (64/197 participants (32.5%) in the rhTSH-aided radioiodine group versus 15/124 participants (12.1%) in the radioiodine alone group; RR 2.53, 95% CI 1.52 to 4.20; 6 studies, 321 participants; moderate-certainty evidence in favour of radioiodine alone). A total of 118/197 participants (59.9%) in the rhTSH-aided radioiodine group compared with 60/124 participants (48.4%) in the radioiodine alone group experienced adverse events (random-effects RR 1.24, 95% CI 0.94 to 1.63; 6 studies, 321 participants; fixed-effect RR 1.23, 95% CI 1.02 to 1.49 in favour of radioiodine only; low-certainty evidence). RhTSH-aided radioiodine reduced thyroid volume with a MD of 11.9% (95% CI 4.4 to 19.4; 6 studies, 268 participants; moderate-certainty evidence). One study with 28 participants reported one death in the radioiodine alone group (very-low certainty evidence). No study reported on costs.
AUTHORS' CONCLUSIONS
RhTSH-aided radioiodine treatment for non-toxic multinodular goitre, compared to radioiodine alone, probably increased the risk of hypothyroidism but probably led to a greater reduction in thyroid volume. Data on QoL and costs were sparse or missing.
Topics: Female; Goiter; Humans; Iodine Radioisotopes; Quality of Life; Randomized Controlled Trials as Topic; Thyrotropin; Thyrotropin Alfa
PubMed: 34961921
DOI: 10.1002/14651858.CD010622.pub2 -
Renal Failure Dec 2023This cohort study was designed to explore whether roxadustat or erythropoietin could affect thyroid function in patients with renal anemia.
PURPOSE
This cohort study was designed to explore whether roxadustat or erythropoietin could affect thyroid function in patients with renal anemia.
METHODS
The study involved 110 patients with renal anemia. Thyroid profile and baseline investigations were carried out for each patient. The patients were divided into two groups: 60 patients taking erythropoietin served as the control group (rHuEPO group) and 50 patients using roxadustat served as the experimental group (roxadustat group).
RESULTS
The results indicated that there were no significant differences in serum total thyroxine (TT4), total triiodothyronine (TT3), free triiodothyronine (FT3), free thyroxine (FT4) or thyroid stimulating hormone (TSH) between the two groups at baseline. After treatment, TSH, FT3, and FT4 were significantly lower in the roxadustat group than in the rHuEPO group ( < 0.05). After adjusting for age, sex, dialysis modality, thyroid nodules and causes of kidney disease, Cox regression showed that roxadustat was an independent influencing factor on thyroid dysfunction (HR 3.37; 95% CI 1.94-5.87; < 0.001). After 12 months of follow-up, the incidence of thyroid dysfunction was higher in the roxadustat group than in the rHuEPO group (log-rank < 0.001).
CONCLUSION
Roxadustat may lead to a higher risk of thyroid dysfunction, including low TSH, FT3 and FT4, than rHuEPO in patients with renal anemia.
Topics: Humans; Triiodothyronine; Thyroxine; Thyroid Gland; Cohort Studies; Thyrotropin; Erythropoietin; Chronic Disease; Kidney Diseases; Epoetin Alfa; Anemia
PubMed: 37051660
DOI: 10.1080/0886022X.2023.2199093 -
Endocrine Practice : Official Journal... 2013In order to effectively treat differentiated thyroid cancer (DTC) with radioiodine (RAI) it is necessary to raise serum TSH levels either endogenously by thyroid hormone... (Review)
Review
OBJECTIVE
In order to effectively treat differentiated thyroid cancer (DTC) with radioiodine (RAI) it is necessary to raise serum TSH levels either endogenously by thyroid hormone withdrawal (THW) or exogenously by administration of recombinant human TSH (rhTSH). The goal of this review is to present current data on the relative efficacy and side effects profile of rhTSH-aided versus THW-aided RAI therapy for the treatment of patients with distant metastases of DTC.
METHODS
We have searched the PubMed database for articles including the keywords "rhTSH", "thyroid cancer", and "distant metastases" published between January 1, 1996 and January 7, 2012. As references, we used clinical case series, case reports, review articles, and practical guidelines.
RESULTS
Exogenous stimulation of TSH is associated with better quality of life because it obviates signs and symptoms of hypothyroidism resulting from endogenous TSH stimulation. The rate of neurological complications after rhTSH and THW-aided RAI therapy for brain and spine metastases is similar. The rate of leukopenia, thrombocytopenia, xerostomia, and pulmonary fibrosis is similar after preparation for RAI treatment with rhTSH and THW. There is currently a controversy regarding RAI uptake in metastatic lesions after preparation with rhTSH versus THW, with some studies suggesting equal and some superior uptake after preparation with THW. Analysis of available retrospective studies comparing survival rates, progression free survival, and biochemical and structural response to a dosimetrically-determined dose of RAI shows similar efficacy after preparation for therapy with rhTSH and THW.
CONCLUSION
The rhTSH stimulation is not presently approved by the FDA as a method of preparation for adjunctive therapy with RAI in patients with metastatic DTC. Data on rhTSH compassionate use suggest that rhTSH stimulation is as equally effective as THW as a method of preparation for dosimetry-based RAI treatment in patients with RAI-avid metastatic DTC.
Topics: Humans; Neoplasm Metastasis; Thyroid Neoplasms; Thyrotropin Alfa
PubMed: 23186979
DOI: 10.4158/EP12244.RA -
Journal of Nuclear Medicine : Official... Oct 2022It is well known that ionizing radiation can induce genetic damage and that oxidative stress is a major factor inducing it. Our aim was to investigate whether thyroid...
Analysis of Short-Term and Stable DNA Damage in Patients with Differentiated Thyroid Cancer Treated with I in Hypothyroidism or with Recombinant Human Thyroid-Stimulating Hormone for Remnant Ablation.
It is well known that ionizing radiation can induce genetic damage and that oxidative stress is a major factor inducing it. Our aim was to investigate whether thyroid remnant ablation with low activities of I (1,850 MBq) is associated with DNA damage by evaluating the CometAssay, micronuclei, and chromosome aberrations with multicolor fluorescent in situ hybridization. We studied 62 patients prepared with recombinant human thyroid-stimulating hormone (rhTSH) or by thyroid hormone withdrawal. In both groups, we analyzed stable and unstable genetic alterations before I therapy and 1 wk and 3 mo after I administration. We also correlated the genetic damage with several variables, including the degree of radiation-induced oxidative stress, genetic polymorphisms of enzymes involved in DNA repair, and antioxidative stress. We found a comparable amount of DNA breaks evaluated by CometAssay and micronuclei testing in both groups of patients at different time points, but there was a significant increase in stable chromosome aberrations evaluated by multicolor fluorescent in situ hybridization (breaks and translocations) in patients prepared with thyroid hormone withdrawal. Overall, high chromosome damage was associated with higher retained body radioactivity and unfavorable gene polymorphism. A high level of free oxygen radicals and a low level of antioxidants were found in all patients at any time point. In particular, patients prepared with thyroid hormone withdrawal, at 3 mo, had significantly higher levels of free oxygen radicals than those prepared with rhTSH. An increase in stable chromosome aberrations with respect to baseline is detectable after administration of low doses of I in patients prepared with thyroid hormone withdrawal but not in patients prepared with rhTSH. The clinical significance of these chromosomal alterations remains to be determined.
Topics: Adenocarcinoma; Chromosome Aberrations; DNA Damage; Humans; Hypothyroidism; In Situ Hybridization, Fluorescence; Iodine Radioisotopes; Reactive Oxygen Species; Thyroid Hormones; Thyroid Neoplasms; Thyrotropin; Thyrotropin Alfa
PubMed: 35115370
DOI: 10.2967/jnumed.121.263442 -
Japanese Journal of Radiology Nov 2023Thyroid hormone withdrawal (THW) in preparation for radioactive iodine therapy (RIT) may lead to hyponatremia and hyperkalemia because hypothyroidism reduces the...
PURPOSE
Thyroid hormone withdrawal (THW) in preparation for radioactive iodine therapy (RIT) may lead to hyponatremia and hyperkalemia because hypothyroidism reduces the glomerular filtration rate. Using recombinant human thyrotropin (rhTSH) may avoid these changes; however, these two preparation methods have not been compared in the literature. The purpose of this study was to reveal whether THW and rhTSH as preparation methods for RIT affect serum electrolytes differently. We also evaluated clinical factors influencing the onset of hyponatremia and hyperkalemia during RIT.
MATERIALS AND METHODS
From April 2005 to December 2020, we analyzed 278 patients with thyroid cancer who received RIT. The patients were classified into two groups based on the preparation method, and renal function and serum electrolytes were compared between the groups. We also evaluated clinical factors that may affect overt hyponatremia (serum sodium level < 134 mmol/L) and hyperkalemia (serum potassium level ≥ 5.0 mmol/L).
RESULTS
Serum sodium and chloride levels in the THW group were significantly lower than those in the rhTSH group (p < 0.001 and p = 0.002, respectively). In contrast, the serum potassium level in the THW group was significantly higher than that in the rhTSH group (p = 0.008). As for clinical factors that may influence hyponatremia, age and estimated glomerular filtration rate (eGFR) were significantly associated with serum sodium level in the univariate analysis (p = 0.033 and p = 0.006, respectively). In the multivariate analysis, only age was significantly associated with serum sodium level (p = 0.030). Regarding hyperkalemia, distant metastases, the preparation method and eGFR were significantly associated with the serum potassium level in the univariate analysis (p = 0.005, p = 0.005 and p = 0.001, respectively). In the multivariate analysis, only eGFR was significantly associated with hyperkalemia (p = 0.019).
CONCLUSION
THW and rhTSH affect serum sodium and potassium levels differently. Renal function may be risk factors for hyperkalemia, whereas older age may be a risk factor for hyponatremia.
Topics: Humans; Thyroid Neoplasms; Thyrotropin Alfa; Iodine Radioisotopes; Hyperkalemia; Hyponatremia; Retrospective Studies; Thyrotropin; Potassium; Sodium; Electrolytes
PubMed: 37184818
DOI: 10.1007/s11604-023-01444-9