Response to [90Yttrium-DOTA]-TOC Treatment is Associated with Long-term Survival Benefit in Metastasized Medullary Thyroid Cancer: A Phase II Clinical Trial

Iten, Fabienne; Müller, Beat; Schindler, Christian; Rochlitz, Christoph; Oertli, Daniel; Mäcke, Helmut R.; Müller-Brand, Jan; Walter, Martin A.

doi:10.1158/1078-0432.ccr-07-0935

Cited by 152 publications

(105 citation statements)

References 20 publications

(20 reference statements)

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“…However, according to published clinical data, tumor doses and tumor-to-normal-tissue ratios seem to be higher with pretargeting than with directly radiolabeled anti-CEA mAb (9,10,14). 90 Y-DOTATOC induced in 31 progressive metastatic MTC patients a biomarker response in 58% (24). However, only 60%-70% of MTC tumors express somatostatin receptors, whereas .90% of MTCs express CEA.…”

Section: Discussionmentioning

confidence: 99%

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Phase II Trial of Anticarcinoembryonic Antigen Pretargeted Radioimmunotherapy in Progressive Metastatic Medullary Thyroid Carcinoma: Biomarker Response and Survival Improvement

Salaun¹,

Campion²,

Bournaud³

et al. 2012

J Nucl Med

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The prognosis of medullary thyroid carcinoma (MTC) varies from long-to short-term survival based on such prognostic factors as serum calcitonin and carcinoembryonic antigen (CEA) doubling times (DTs). This prospective phase II multicenter trial evaluated the efficacy and safety of anti-CEA pretargeted radioimmunotherapy (pRAIT) in rapidly progressing metastatic MTC patients and also how serum biomarker DTs correlate with clinical outcome. Methods: From June 2004 to January 2008, 42 patients were treated with anti-CEA · anti-diethylenetriaminepentaacetic acid (DTPA) bispecific antibody (hMN-14 · m734) (40 mg/m 2 ), followed by 131 I-di-DTPA-indium bivalent hapten (1.8 GBq/m 2 ) 4-6 d later. Results: The disease control rate (durable stabilization plus objective response) was 76.2%. Grade 3-4 hematologic toxicity was observed in 54.7% of patients and myelodysplastic syndrome in 2, including 1 heavily treated previously. After pRAIT, 21 of 37 assessed patients (56.7%) showed a significant impact on DT ($100% increase of pre-pRAIT calcitonin or CEA DT or prolonged decrease of the biomarker concentration after pRAIT). Pre-pRAIT DT and postpRAIT DT were significant independent predictors for overall survival (OS) from pRAIT (pre-pRAIT: hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.24-0.86; P 5 0.016; and postpRAIT: HR, 5.32; 95% CI, 1.63-17.36; P 5 0.006) and OS from diagnosis (pre-pRAIT: HR, 0.21; 95% CI, 0.08-0.51; P 5 0.001; and post-pRAIT: HR, 6.16; 95% CI, 1.81-20.98; P 5 0.004). Conclusion: pRAIT showed antitumor activity, with manageable hematologic toxicity in progressive MTC. Increased biomarker DT after treatment correlated with increased OS.

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Section: Discussionmentioning

confidence: 99%

“…Several targeted therapies have been assessed recently in MTC (4)(5)(6)(7)(8)(9)(10)24,25). Tumor responses have been reported with directly radiolabeled anti-CEA mAb, but the comparison with pRAIT remains difficult because the eligibility criteria were different (9,10,14).…”

Section: Discussionmentioning

confidence: 99%

Phase II Trial of Anticarcinoembryonic Antigen Pretargeted Radioimmunotherapy in Progressive Metastatic Medullary Thyroid Carcinoma: Biomarker Response and Survival Improvement

Salaun¹,

Campion²,

Bournaud³

et al. 2012

J Nucl Med

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“…90 Yttrium-labeled DOTA-TOC (edotreotide) binds to SSTR subtype 2 on the surface of MTC tumor cells, and emits β-radiation that causes cytotoxicity. In a Phase II trial, 29% patients with metastatic MTC responded to the 90 Yttrium-DOTA-TOC treatment, and response to the treatment was associated with a longer survival from time of diagnosis and time of first treatment [62]. Therapy with 177 Lutetium-DOTATATE, a similar type of peptide receptor radionuclide targeting the SSTR, was reported to achieve stable disease for 9-10 months in two cases [63].…”

Section: • Radionuclide Therapymentioning

confidence: 99%

Recent Advances in the Management of Endocrine Malignancies Associated with Hereditary Hyperparathyroidism Syndromes

Li¹,

Simonds

2017

Int. J. Endo. Oncol.

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Hereditary hyperparathyroidism syndromes, such as multiple endocrine neoplasm type 1, type 2A and the hyperparathyroidism-jaw tumor syndrome, are associated with an increased incidence of malignancies involving the neuroendocrine tissue of the pancreas and thymus, parathyroid and thyroid glands. The natural history of these endocrine tumors can differ from nonhereditary malignancies. The surgical approach, the only potentially curative treatment option for these endocrine malignancies, has evolved considerably in recent years. Newer targeted therapies, such as small molecule kinase inhibitors, somatostatin analogs and peptide receptor radionuclide therapy, are being developed. We provide here a comprehensive review of the current standards of treatment and emerging novel therapies for the endocrine malignancies commonly associated with hereditary hyperparathyroidism syndromes.

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“…The results obtained with 90 Y and 177 Lu-DOTATOC are encouraging in terms of tumour regression and symptomatic improvement [1][2][3][4][5][6][7]. If reno-protective agents are used, the side effects of PRRT are few and transient.…”

Section: Introductionmentioning

confidence: 99%

Monitoring and Predicting Response to Peptide Receptor Radionuclide Therapy: A Quantitative SPECT-CT Based Analysis~!2009-12-10~!2010-02-04~!2010-04-21~!

Chinnadurai¹,

Berg²,

Nicolas³

et al. 2010

TONMEDJ

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Abstract:Purpose: A standard imaging protocol for monitoring and predicting the response to Peptide Receptor Radionuclide Therapy (PRRT) has not been established yet. The aim of this study was to evaluate the response to PRRT by quantitative SPECT-CT and assess the value of SPECT-CT over routine planar scintigraphy in predicting the outcome of PRRT.Methods: 32 patients with neuroendocrine tumour, who underwent SPECT-CT imaging after the first and second course of radiolabelled DOTATOC were retrospectively analysed. The response to therapy was defined by decrease in tumour volume in CT. The uptake in planar scintigraphy was evaluated by visual assessment based on a 5-point scoring scale. From SPECT images, ratios of maximum and mean values of tumour uptake to normal liver uptake were calculated. The value of SPECT-CT over planar scintigraphy in predicting therapy response was assessed by Receiver Operating Characteristic (ROC) analysis.Results: Evaluation of 77 target lesions (in 32 patients) by SPECT-CT imaging, showed that the mean uptake ratio decreased from a median value of 5.66 (range 0.5 to 32.37) to 3.85 (range 0.95 to 15.75), with an overall 26 % decrease (P < 0.001). The maximum uptake ratio decreased from a median value of 7.98 (0.97 to 54.21) to 5.59 (1.95 to 29.71), with an overall 30 % decrease (P < 0.002). On evaluation of 67 measurable lesions by CT (in 23 patients), the tumour volume decreased from a median value of 58.5 cm 3 (14.1 to 411.7) to 38.3 cm 3 (9.9 to 428.4) with an overall 35 % decrease (P = 0.001). The area under the ROC curve was 0.733 (95 % Confidence Interval: 0.203, 0.819) for SPECT-CT and 0.551 (95 % Confidence Interval: 0.485, 0.981) for planar scintigraphy. Conclusion:Our results highlight the value of SPECT-CT in monitoring, quantitative evaluation of response to PRRT and its superiority in the prediction of decrease in tumour volume. The initial tumour uptake ratio from SPECT-CT could serve as a prognostic factor in the prediction of response to PRRT.

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Response to [90Yttrium-DOTA]-TOC Treatment is Associated with Long-term Survival Benefit in Metastasized Medullary Thyroid Cancer: A Phase II Clinical Trial

Abstract: Purpose: We aimed to explore the efficacy of 90 Yttrium^1,4,7,N ¶,N

Cited by 152 publications

References 20 publications

Phase II Trial of Anticarcinoembryonic Antigen Pretargeted Radioimmunotherapy in Progressive Metastatic Medullary Thyroid Carcinoma: Biomarker Response and Survival Improvement

Phase II Trial of Anticarcinoembryonic Antigen Pretargeted Radioimmunotherapy in Progressive Metastatic Medullary Thyroid Carcinoma: Biomarker Response and Survival Improvement

Recent Advances in the Management of Endocrine Malignancies Associated with Hereditary Hyperparathyroidism Syndromes

Monitoring and Predicting Response to Peptide Receptor Radionuclide Therapy: A Quantitative SPECT-CT Based Analysis~!2009-12-10~!2010-02-04~!2010-04-21~!

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