scholarly journals Beneficial effects of sorafenib on tumor progression, but not on radioiodine uptake, in patients with differentiated thyroid carcinoma

2009 ◽  
Vol 161 (6) ◽  
pp. 923-931 ◽  
Author(s):  
Hendrieke Hoftijzer ◽  
Karen A Heemstra ◽  
Hans Morreau ◽  
Marcel P Stokkel ◽  
Eleonora P Corssmit ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Bone Metastases ◽  
Tumor Progression ◽  
Kinase Inhibitor ◽  
Treatment Options ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Differentiated Thyroid Carcinoma ◽  
Whole Body ◽  
Mutational Status

ObjectiveTreatment options for patients with radioactive iodine (RaI) refractory metastases of differentiated thyroid carcinoma (DTC) are limited. We studied the effects of the multitarget tyrosine kinase inhibitor sorafenib on the reinduction of RaI uptake and tumor progression.DesignOpen, single center, single arm 26-week prospective phase II study with open-ended extension.MethodsWe treated 31 patients with progressive metastatic or locally advanced RaI refractory DTC with sorafenib 400 mg b.i.d. The primary endpoint was reinduction of RaI uptake at 26 weeks. Additional endpoints were the radiological response and the influence of bone metastases.ResultsAt 26 weeks of sorafenib therapy, no reinduction of RaI uptake at metastatic sites was observed, but 19 patients (59%) had a clinical beneficial response, eight of whom had a partial response (25%) and 11 had stable disease (34%). Seven patients had progressive disease (22%). Sorafenib was significantly less effective in patients with bone metastases. The estimated median progression free survival was 58 weeks (95% confidence interval, CI, 47–68). In general, thyroglobulin (Tg) response (both unstimulated and TSH stimulated) reflected radiological responses. The median time of the nadir of Tg levels was 3 months. Responses were not influenced by histological subtype, mutational status or other variables. No unusual side effects were observed.ConclusionsSorafenib has a beneficial effect on tumor progression in patients with metastatic DTC, but was less effective in patients with bone metastases. Diagnostic whole body scintigraphy did not reveal an effect of sorafenib on the reinduction of RaI uptake.

scholarly journals Analysis of the efficacy and toxicity of sorafenib in thyroid cancer: a phase II study in a UK based population

2011 ◽  
Vol 165 (2) ◽  
pp. 315-322 ◽  
Author(s):  
Merina Ahmed ◽  
Yolanda Barbachano ◽  
Angela Riddell ◽  
Jen Hickey ◽  
Katie L Newbold ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Carcinoma ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Differentiated Thyroid Carcinoma ◽  
Free Survival ◽  
Hand Foot Syndrome ◽  
Secondary Endpoints ◽  
Radiological Response ◽  
Dose Reductions

AimTo evaluate the tolerability and efficacy of sorafenib in patients with thyroid carcinoma.MethodsPatients with progressive locally advanced/metastatic medullary thyroid carcinoma (MTC), or differentiated thyroid carcinoma (DTC) with non-radioiodine-avid disease, were treated with sorafenib 400 mg twice daily until disease progression. The primary endpoint was the radiological response rate (RR) at 6 months. Secondary endpoints were RR at 3, 9 and 12 months, biochemical responses, toxicity, biomarker analyses and progression free and overall survival (OS).ResultsA total of 34 patients were recruited to the study (15 medullary and 19 differentiated). After 6 months, the RR rate was 15% and a further 74% of patients achieved stable disease in the first 6 months. After 12 months of treatment, the RR was 21%. In the MTC patients, the RR at 12 months was 25% and OS was 100%. In DTC patients corresponding rates were 18 and 79% respectively. Median overall and progression-free survival points were not reached at 19 months. Commonest adverse events included hand–foot syndrome, other skin toxicities, diarrhoea and alopecia. Dose reduction was required in 79% patients. Median time on treatment was 16.5 months.ConclusionThis study demonstrates that sorafenib is tolerable at reduced doses over prolonged periods of time in patients with thyroid cancer. Sorafenib leads to radiological and biochemical stabilisation of disease in the majority of these patients despite dose reductions.

scholarly journals Bexarotene increases uptake of radioiodide in metastases of differentiated thyroid carcinoma

2006 ◽  
Vol 154 (4) ◽  
pp. 525-531 ◽  
Author(s):  
Ying Y Liu ◽  
Marcel P Stokkel ◽  
Alberto M Pereira ◽  
Eleonora P Corssmit ◽  
Hans A Morreau ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Single Photon ◽  
Treatment Options ◽  
Photon Emission ◽  
Ct Scanning ◽  
Differentiated Thyroid Carcinoma ◽  
Whole Body ◽  
Iodide Uptake ◽  
Beneficial Effects

Objective: Treatment options for metastases of differentiated thyroid carcinoma (DTC) are limited due to decreased uptake of radioiodide (I-131). Therefore, strategies to improve I-131 uptake are mandatory. It has been suggested that retinoids have beneficial effects on iodide uptake in vitro and in humans. However, to date, only studies with 13-cis-retinoic acid have been performed in humans. We therefore decided to study the effects of 6 weeks of treatment with the retinoid X receptor activator bexarotene on I-131 uptake in patients with metastatic DTC. Design: Open prospective intervention study. Methods: Twelve patients with metastases of DTC, with insufficient uptake of I-131, received 6 weeks of treatment with 300 mg bexarotene/day. Prior to, and after this intervention, I-131 uptake was measured by whole-body scintigraphy and single photon emission tomography (SPECT) 3 days after 185 MBq I-131. Diagnostic imaging was preceded by two consecutive injections of recombinant human TSH. Results: Bexarotene treatment induced I-131 uptake in metastases of 8 out of 11 patients (one patient died for reasons not related to the study). However, uptake was only discernable at SPECT and had incomplete matching with metastases as visualized by CT scanning. Conclusions: Bexarotene partially restores I-131 uptake in metastases of DTC. The clinical relevance of this observation may be limited due to the differential responses of the different metastases within each patient and the low intensity of I-131 uptake.

131J-speichernde pulmonale und ossäre Metastasen differenzierter Schilddrüsenkarzinome bei niedrigem Serum-Thyreoglobulinspiegel – Ausnahme in der Tumornachsorge?

1987 ◽  
Vol 26 (03) ◽  
pp. 139-142 ◽  
Author(s):  
G. Arning ◽  
O. Schober ◽  
H. Hundeshagen ◽  
Ch. Ehrenheim
Keyword(s):  
Serum Level ◽  
Thyroid Carcinoma ◽  
Bone Metastases ◽  
Differentiated Thyroid Carcinoma ◽  
Serum Thyroglobulin ◽  
Thyroglobulin Level ◽  
Low Serum

In the follow-up of differentiated thyroid carcinoma it is discussed whether the tumormarker thyroglobulin can replace the1311 scan, especially when the thyroglobulin serum level is normal. A positive1311 scan of metastases in the follow-up of patients with differentiated thyroid carcinoma combined with a low serum thyroglobulin level is extremely rare. The literature shows a frequency of about 4%. Recently we found 3 cases with a positive1311 scan demonstrating pulmonary and bone metastases whereas the serum thyroglobulin level was low.

scholarly journals Radioiodine in Differentiated Thyroid Carcinoma: Do We Need Diagnostic Pre-Ablation Iodine-123 Scintigraphy to Optimize Treatment?

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 553
Author(s):  
Elizabeth de Koster ◽  
Taban Sulaiman ◽  
Jaap Hamming ◽  
Abbey Schepers ◽  
Marieke Snel ◽  
...  
Keyword(s):  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Thyroid Carcinoma ◽  
Treatment Success ◽  
Differentiated Thyroid Carcinoma ◽  
Whole Body ◽  
Thyroid Remnant ◽  
Node Metastasis ◽  
Unsuccessful Treatment

Changing insights regarding radioiodine (I-131) administration in differentiated thyroid carcinoma (DTC) stir up discussions on the utility of pre-ablation diagnostic scintigraphy (DxWBS). Our retrospective study qualitatively and semi-quantitatively assessed posttherapy I-131 whole-body scintigraphy (TxWBS) data for thyroid remnant size and metastasis. Findings were associated with initial treatment success after nine months, as well as clinical, histopathological, and surgical parameters. Possible management changes were addressed. A thyroid remnant was reported in 89 of 97 (92%) patients, suspicion of lymph node metastasis in 26 (27%) and distant metastasis in 6 (6%). Surgery with oncological intent and surgery by two dedicated thyroid surgeons were independently associated with a smaller remnant. Surgery at a community hospital, aggressive tumor histopathology, histopathological lymph node metastasis (pN1) and suspicion of new lymph node metastasis on TxWBS were independently associated with an unsuccessful treatment. Thyroid remnant size was unrelated to treatment success. All 13 pN1 patients with suspected in situ lymph node metastases on TxWBS had an unsuccessful treatment, opposite 19/31 (61%) pN1 patients without (p = 0.009). Pre-ablative knowledge of these TxWBS findings had likely influenced management in 48 (50%) patients. Additional pre-ablative diagnostics could optimize patient-tailored I-131 administration. DxWBS should be considered, especially in patients with pN1 stage or suspected in situ lymph node metastasis. Dependent on local surgical expertise, DxWBS is not recommended to evaluate thyroid remnant size.

scholarly journals Questions and Controversies in the Clinical Application of Tyrosine Kinase Inhibitors to Treat Patients with Radioiodine-Refractory Differentiated Thyroid Carcinoma: Expert Perspectives

2021 ◽  
Vol 53 (03) ◽  
pp. 149-160
Author(s):  
Frederik A. Verburg ◽  
Holger Amthauer ◽  
Ina Binse ◽  
Ingo Brink ◽  
Andreas Buck ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Performance Status ◽  
Progression Free Survival ◽  
Placebo Treatment ◽  
Differentiated Thyroid Carcinoma ◽  
Future Research ◽  
Prospective Comparison

AbstractNotwithstanding regulatory approval of lenvatinib and sorafenib to treat radioiodine-refractory differentiated thyroid carcinoma (RAI-R DTC), important questions and controversies persist regarding this use of these tyrosine kinase inhibitors (TKIs). RAI-R DTC experts from German tertiary referral centers convened to identify and explore such issues; this paper summarizes their discussions. One challenge is determining when to start TKI therapy. Decision-making should be shared between patients and multidisciplinary caregivers, and should consider tumor size/burden, growth rate, and site(s), the key drivers of RAI-R DTC morbidity and mortality, along with current and projected tumor-related symptomatology, co-morbidities, and performance status. Another question involves choice of first-line TKIs. Currently, lenvatinib is generally preferred, due to greater increase in progression-free survival versus placebo treatment and higher response rate in its pivotal trial versus that of sorafenib; additionally, in those studies, lenvatinib but not sorafenib showed overall survival benefit in subgroup analysis. Whether recommended maximum or lower TKI starting doses better balance anti-tumor effects versus tolerability is also unresolved. Exploratory analyses of lenvatinib pivotal study data suggest dose-response effects, possibly favoring higher dosing; however, results are awaited of a prospective comparison of lenvatinib starting regimens. Some controversy surrounds determination of net therapeutic benefit, the key criterion for continuing TKI therapy: if tolerability is acceptable, overall disease control may justify further treatment despite limited but manageable progression. Future research should assess potential guideposts for starting TKIs; fine-tune dosing strategies and further characterize antitumor efficacy; and evaluate interventions to prevent and/or treat TKI toxicity, particularly palmar-plantar erythrodysesthesia and fatigue.

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