Targeting and Treatment of Medullary Thyroid Cancer With I-131-Labeled Murine Anti-Cea Monoclonal Antibodies

Juweid, Malik; Sharkey, Robert M.; Rubin, Arnold D.; Behr, T.; Dunlop, D.G.; Dunn, Robert M.; Vagg, Rae; Goidenberg, D. M.

doi:10.1097/00002371-199408000-00063

Cited by 18 publications

(24 citation statements)

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“…Moreover, this population with frequent bone marrow involvement does not allow demonstration of improved of safety with pRAIT, because the hematologic toxicity is due to the specific uptake of mAb by tumor cells in bone marrow. 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).…”

Section: Discussionmentioning

confidence: 97%

“…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%

“…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). Moreover, this population with frequent bone marrow involvement does not allow demonstration of improved of safety with pRAIT, because the hematologic toxicity is due to the specific uptake of mAb by tumor cells in bone marrow.…”

Section: Discussionmentioning

confidence: 99%

“…Radioimmunotherapy has shown promising results in MTC using anti-CEA monoclonal antibodies (mAbs) (9,10). Pretargeted radioimmunotherapy (pRAIT) was developed to improve the therapeutic index (tumor-to-normaltissue ratios) and to deliver increased tumor-absorbed doses to solid tumors, which are more radioresistant than indolent lymphomas (11,12).…”

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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: 97%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

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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“…[1][2][3][4] Clinical response in solid tumors has not been as promising. [5][6][7] Efforts to improve the outcome with RAIT include the development of combination therapy strategies that use RAIT and a second modality of therapy. The primary focus has been on the use of chemotherapy with RAIT.…”

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confidence: 99%

Optimizing the use of combined radioimmunotherapy and hypoxic cytotoxin therapy as a function of tumor hypoxia

et al. 2001

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Combined radioimmunotherapy (RAIT) and hypoxic cytotoxin therapy (SR4233 or NLCQ-1) have been evaluated with both modalities administered on the same day with only moderate improvement compared with the effects of RAIT alone. In a series of studies using oxygen electrodes, immunohistochemistry and radiotracers, we have demonstrated that RAIT induces a prolonged state of hypoxia in most tumors, without affecting the pO 2 levels in normal tissues. Using serial microelectrode measurements through subcutaneous (s.c.) GW-39 human colonic xenografts, we established that the median pO 2 was unrelated to the initial size of the tumor, over a range of sizes from 1.0 to 4.0 cm. Fourteen days after mice were given a 240-Ci dose of 131 I-MN-14 anti-carcinoembryonic antigen immunoglobulin G, their median pO 2 declined from 26.1 ؎ 9.6 mmHg to 9.8 ؎ 3.9 mmHg (p < 0.001). Using the radiotracer 3 H-MISO that accumulates in hypoxic regions, uptake in GW-39, LoVo and LS174T s.c. human colonic tumors increased 3.0-to 4.2-fold from day 14 through day 28 post-RAIT, but uptake of 3 H-MISO in CALU-3 tumors remained unchanged after RAIT. Normal tissue (liver, kidney, lung) uptake of 3 H-MISO did not exhibit significant changes. The increase in tumor hypoxia was also demonstrated visually using anti-PIMO staining of tumor sections. We postulated that sequential delivery of the 2 therapeutic agents, with the hypoxic cytotoxin given 2 weeks after RAIT when tumor pO 2 levels were at their nadir, would improve the therapeutic response above either modality alone or above the 2 agents delivered on the same day. Tumor growth was compared in mice given either RAIT or cytotoxin alone, the combined treatment on the same day or with the cytotoxin delivered 14 days after RAIT. Tumor size on day 35 for RAIT-treated and SR4233-treated GW-39 were 3.56 ؎ 0.40 and 7.98 ؎ 2.50 cm 3 . When RAIT ؉ SR4233 were delivered on the same day, tumor size dropped to 2.78 ؎ 0.80 cm 3 . If RAIT was given on day 0 and SR4233 on day 14, size further declined further to 1.74 ؎ 0.32 cm 3 (p < 0.05 compared with same day delivery). For LS174T, tumor size on day 28 for RAIT-treated and SR4233-treated tumors were 1.14 ؎ 0.36 cm 3 and 3.65 ؎ 0.78 cm 3 , respectively. When RAIT ؉ SR4233 were delivered on the same day, size was 0.51 ؎ 0.174 cm 3 . If RAIT was dosed on day 0 and SR4233 was given on day 14, tumor size was 0.13 ؎ 0.07 cm 3 (p < 0.05). Similar results were obtained for LoVo, but not for CALU-3 tumors. Another hypoxic cytotoxin, NLCQ-1, was also more efficacious 2 weeks after RAIT, compared with same-day dosing. Thus, information on tumor hypoxia after radioantibody therapy could be important for ascertaining a window of opportunity when the surviving tumor regions are most responsive to hypoxic cytotoxins.

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Detection of Medullary Thyroid Carcinoma and Regional Lymph Node Metastases by Magnetic Resonance Imaging

Wang

Takashima²,

Fukuda³

et al. 1999

Arch Otolaryngol Head Neck Surg

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Targeting and Treatment of Medullary Thyroid Cancer With I-131-Labeled Murine Anti-Cea Monoclonal Antibodies

Cited by 18 publications

References 0 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

Optimizing the use of combined radioimmunotherapy and hypoxic cytotoxin therapy as a function of tumor hypoxia

Detection of Medullary Thyroid Carcinoma and Regional Lymph Node Metastases by Magnetic Resonance Imaging

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