scholarly journals Associations Between Plasma Concentrations of Lenvatinib and Angiopoietin and Clinical Responses to Lenvatinib Therapy in Japanese Patients With Thyroid Cancer

2021 ◽  
Author(s):  
Maho Kumagai ◽  
Mitsuji Nagahama ◽  
Yumiko Akamine ◽  
Tomoko Ozeki ◽  
Akifumi Suzuki ◽  
...  
Keyword(s):  
Overall Survival ◽  
Thyroid Cancer ◽  
Progressive Disease ◽  
Plasma Concentrations ◽  
Japanese Patients ◽  
Inhibitory Effect ◽  
Change Rate ◽  
Clinical Responses ◽  
One Year ◽  
Median Change

Abstract Purpose: The purpose of this study was to investigate the relationships among plasma concentrations of lenvatinib, angiopoietin (Ang)-1 and Ang-2, and clinical responses to lenvatinib therapy in Japanese patients with thyroid cancer. Methods: Plasma concentrations of lenvatinib (C0) and Ang-1 and -2 were measured by HPLC and ELISA, respectively.Results: The median change rates of Ang-1 and Ang-2 at 1 month after treatment from baseline in 36 patients were -15.3% and -48.4%, respectively. However, the change of Ang-1 and Ang-2 at 1 month from baseline did not correlate with lenvatinib C0. In patients with partial response (PR) and stable disease to lenvatinib, Ang-2 at 1 month were significantly lower than Ang-2 at baseline (P < 0.001 and P < 0.05, respectively), but were not significantly lower in patients with progressive disease. The area under the ROC for PR prediction was 0.667, giving the best sensitivity (69.2%) and specificity (73.9%) at a threshold of the change rate of Ang-2 of -49.83%. A one year overall survival for patients having the change rate of Ang-2 of at least -49.83% and less than -49.83% were 62.5% and 40%, respectively. In patients who continued treatment with lenvatinib for 1 year, Ang-2 at 1 month and 1 year after treatment were significantly lower than those at baseline (each P < 0.001).Conclusion: The change of Ang-2 at 1 month after treatment from baseline rather than simply the Ang-2 level at baseline may be important as a biomarker of the inhibitory effect of angiogenesis by lenvatinib.

scholarly journals Associations between plasma concentrations of lenvatinib and angiopoietin and clinical responses to lenvatinib therapy in Japanese patients with thyroid cancer

2021 ◽  
Author(s):  
Maho Kumagai ◽  
Mitsuji Nagahama ◽  
Yumiko Akamine ◽  
Tomoko Ozeki ◽  
Akifumi Suzuki ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Partial Response ◽  
Cancer Patients ◽  
Progressive Disease ◽  
Plasma Concentrations ◽  
Japanese Patients ◽  
Inhibitory Effect ◽  
Change Rate ◽  
Clinical Responses ◽  
Median Change

Abstract The purpose of this study was to investigate the relationships among plasma concentrations (C0) of lenvatinib, angiopoietin (Ang)-1 and Ang-2, and clinical responses to lenvatinib therapy in thyroid cancer patients. The median change rates of Ang-1 and Ang-2 at 1 month after treatment from baseline in all patients were − 15.3% and − 48.4%, respectively. However, the change of Ang-1 and Ang-2 at 1 month from baseline did not correlate with lenvatinib C0. In patients with partial response (PR) and stable disease to lenvatinib, Ang-2 at 1 month were significantly lower than Ang-2 at baseline (P < 0.001 and P < 0.05, respectively), but were not significantly lower in patients with progressive disease. The area under the ROC for PR prediction was 0.667, giving the best sensitivity (69.2%) and specificity (73.9%) at a threshold of the change rate of Ang-2 of -49.83%. In patients who continued treatment with lenvatinib for 1 year, Ang-2 at 1 month and 1 year were significantly lower than those at baseline (each P < 0.001). The change of Ang-2 at 1 month after treatment from baseline rather than simply the Ang-2 level at baseline may be important as a biomarker of the inhibitory effect of angiogenesis by lenvatinib.

Association of lenvatinib trough plasma concentrations with lenvatinib-induced toxicities in Japanese patients with thyroid cancer

2019 ◽  
Vol 36 (5) ◽  
Author(s):  
Mitsuji Nagahama ◽  
Tomoko Ozeki ◽  
Akifumi Suzuki ◽  
Kiminori Sugino ◽  
Takenori Niioka ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Plasma Concentrations ◽  
Japanese Patients ◽  
Trough Plasma

scholarly journals The role of Hashimoto thyroiditis in predicting radioiodine ablation efficacy and prognosis of low to intermediate risk differentiated thyroid cancer

2021 ◽  
Author(s):  
Domenico Albano ◽  
Francesco Dondi ◽  
Valentina Zilioli ◽  
Maria Beatrice Panarotto ◽  
Alessandro Galani ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Treatment Response ◽  
Differentiated Thyroid Cancer ◽  
Hashimoto Thyroiditis ◽  
Prognostic Impact ◽  
Intermediate Risk ◽  
Excellent Response ◽  
Radioiodine Ablation ◽  
One Year

Abstract Objective The baseline treatment of differentiated thyroid cancer (DTC) consists of thyroidectomy followed by postoperative risk-adapted radioiodine therapy (RAIT) when indicated. The choice of most appropriate RAI activities to administer with the aim to reach an efficient remnant ablation and reduce the risk of recurrence is yet an open issue and the detection of basal factors that may predict treatment response seems fundamental. The aim of this study was to investigate the potential role of Hashimoto thyroiditis (HT) in predicting 1-year and 5-year treatment response after RAIT and prognosis. Methods We retrospectively included 314 consecutive patients (174 low-risk and 140 intermediate-risk) who received thyroidectomy plus RAIT. One-year and 5-year disease status was evaluated according to 2015 ATA categories response based upon biochemical and structural findings. Results HT was reported histopathologically in 120 patients (38%). DTC patients with concomitant HT received a higher number of RAITs and cumulative RAI activities. Initial RAIT reached an excellent response in 63% after one year and 84% after 5 years. The rate of excellent response one year and 5-year after first RAIT was significantly lower in HT groups, compared to not HT (p < 0.001). Instead, HT did not have a prognostic role considering PFS and OS; while stimulate thyroglobulin (sTg) at ablation was significantly related to survival. Conclusions HT may affect the efficacy of RAIT in low to intermediate risk DTC, particularly reducing the successful rate of excellent response after RAIT. Instead, HT did not have a prognostic impact such as stimulated sTg.

scholarly journals Poorly Differentiated and Anaplastic Thyroid Cancer: Insights into Genomics, Microenvironment and New Drugs

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3200
Author(s):  
Alessandro Prete ◽  
Antonio Matrone ◽  
Carla Gambale ◽  
Liborio Torregrossa ◽  
Elisa Minaldi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Thyroid Cancer ◽  
Median Overall Survival ◽  
Clinical Problem ◽  
Anaplastic Thyroid Cancer ◽  
New Drugs ◽  
Poor Survival ◽  
Tumor Microenvironments ◽  
Genetic Features ◽  
Poorly Differentiated

PDTC and ATC present median overall survival of 6 years and 6 months, respectively. In spite of their rarity, patients with PDTC and ATC represent a significant clinical problem, because of their poor survival and the substantial inefficacy of classical therapies. We reviewed the newest findings about genetic features of PDTC and ATC, from mutations occurring in DNA to alterations in RNA. Therefore, we describe their tumor microenvironments (both immune and not-immune) and the interactions between tumor and neighboring cells. Finally, we recapitulate how this upcoming evidence are changing the treatment of PDTC and ATC.

Continuation Therapy with Amitriptyline in Depression

1978 ◽  
Vol 133 (1) ◽  
pp. 28-33 ◽  
Author(s):  
A. Coppen ◽  
K. Ghose ◽  
S. Montgomery ◽  
V. A. Rama Rao ◽  
J. Bailey ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Plasma Concentrations ◽  
Antidepressant Medication ◽  
Depressive Illness ◽  
Continuation Therapy ◽  
One Year ◽  
To Receive

SummaryThirty-two patients who had responded to amitriptyline (150 mg daily) when suffering from a depressive illness were allocated either to receive placebo or to remain on the same medication for one year.Plasma concentrations of the drug were regularly estimated. There was no correlation between plasma concentration and subsequent residual affective morbidity. In spite of considerable encouragement, three of the patients did not take the prescribed amitriptyline and they all relapsed. Five out of sixteen patients who received placebo relapsed. None of the patients who continued to take amitriptyline relapsed.It is emphasized that the patients studied were selected, inasmuch as they were apparent responders to amitriptyline. It is concluded that this group of patients should continue to be treated with antidepressant medication for eight months after apparent recovery, and care should be taken to ensure the patients' compliance.

Overall survival benefit from tebentafusp in patients with best response of progressive disease.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9509-9509
Author(s):  
Anthony M. Joshua ◽  
Jean-Francois Baurain ◽  
Sophie Piperno-Neumann ◽  
Paul Nathan ◽  
Jessica Cecile Hassel ◽  
...  
Keyword(s):  
Overall Survival ◽  
Safety Profile ◽  
Progressive Disease ◽  
Analysis Data ◽  
Cell Receptor ◽  
Kaplan Meier ◽  
Immortal Time Bias ◽  
Best Response ◽  
Overall Survival Benefit

9509 Background: Tebentafusp (tebe) is the first T cell receptor (TCR) therapeutic to demonstrate an overall survival (OS) benefit in a randomized Phase 3 (Ph3) study [ NCT03070392 ]. In Ph2, 42% of pts with best overall response (BOR) of progressive disease (PD) survived > 1 year (yr), suggesting RECIST-based radiographic assessments underestimate OS benefit of tebe. Here we analyzed OS in the Ph3 study in a cohort of pts with BOR of PD by comparing tebe to the control arm of investigator’s choice (IC). Methods: 378 pts were randomized in a 2:1 ratio to tebe vs. IC. BOR was assessed by investigators using RECIST v1.1. Treatment beyond first disease progression (TBP) was permitted for both arms. On the IC arm, only patients receiving pembrolizumab (pembro) continued with TBP and were included in the TBP-related analyses. No crossover to tebe was permitted; investigators were free to choose subsequent therapy. This analysis was conducted on the first interim analysis (data extracted Nov-2020). Kaplan-Meier estimates of OS were based on Day 100 landmark to eliminate immortal time bias and to capture majority of the PDs. Results: By Day 100, PD as BOR occurred in 52% (130/252) of tebe pts (PD-tebe) vs. 60% (76/126) of IC pts (PD-IC). Key baseline characteristics including lactate dehydrogenase, alkaline phosphatase, ECOG performance, age, and sex were similar between PD-tebe vs PD-IC. The proportion of pts with PD due to progression of target lesions (TL), non-TL, or new lesions were also similar between the two groups. More pts received TBP among PD-tebe 53% (69/130) vs PD-pembro 16% (10/61). Median duration of TBP was longer for PD-tebe (7 weeks) vs PD-Pembro (3 weeks). The safety profile of PD-tebe pts during TBP was similar to all tebe-treated pts. OS was superior for PD-tebe vs PD-IC, HR = 0.41 (95%CI 0.25-0.66), even when considering key baseline covariates. While some pts had regression of TL despite diagnosis of PD ( < 10% of pts), the OS benefit remained even when limited to pts with best change of tumor growth of TL, HR 0.46 (0.29, 0.73). 58% (75/130) PD-tebe and 52% (40/76) PD-IC pts received subsequent therapies. In a landmark OS analysis of these pts beginning on 1st day of subsequent therapy, prior tebe was associated with better OS vs. prior IC, HR 0.59 (95%CI 0.36-0.96). Conclusions: Tebe is the first TCR therapeutic to demonstrate an OS benefit in a solid tumor. Surprisingly, a strong OS benefit from tebe is observed even in pts with BOR of PD, suggesting that RECIST-based radiographic assessments do not capture the complete benefit from tebe. The safety profile of tebe during TBP was consistent with that for long-term tebe treatment. Clinical trial information: NCT03070392.

Sign in / Sign up

Export Citation Format

Share Document