Thyroid radiation doses during radioimmunotherapy of CEA-expressing tumours with 131I-labelled monoclonal antibodies

Tm, Behr; Me, Juweid; Rm, Sharkey; Rm, Dunn; Ying, Zhiliang; Ws, Becker; Ja, Siegel; Dm, Goldenberg

doi:10.1097/00006231-199609000-00007

Cited by 7 publications

(8 citation statements)

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Section: Discussionsupporting

confidence: 70%

“…Thyroid radiation doses showed a high variability in this communication, as was the case in several earlier radioimmunotherapy studies that used radioiodinated immunoconjugates 21. We were able to show that the maximal iodine uptake in the thyroid was less than 1% of the injected activity, indicating that more than 99% of the thyroid was blocked in all cases 21. No correlation had been found between these thyroid doses and conditions leading to an enhanced exposure to free radioiodine, such as unbound I − in the radioantibody preparation, enhanced metabolic breakdown of the labeled antibody due to human anti‐MAb antibodies (human antimouse antibodies [HAMA], human antichimeric antibodies [HACA], or human antihuman antibodies [HAHA]), or immune complex formation with circulating antigens 21.…”

Section: Discussionmentioning

confidence: 60%

“…We were able to show that the maximal iodine uptake in the thyroid was less than 1% of the injected activity, indicating that more than 99% of the thyroid was blocked in all cases 21. No correlation had been found between these thyroid doses and conditions leading to an enhanced exposure to free radioiodine, such as unbound I − in the radioantibody preparation, enhanced metabolic breakdown of the labeled antibody due to human anti‐MAb antibodies (human antimouse antibodies [HAMA], human antichimeric antibodies [HACA], or human antihuman antibodies [HAHA]), or immune complex formation with circulating antigens 21. However, a relationship between the thyroid doses and the patients' compliance in taking their cold iodide‐blocking medications was found 21.…”

Section: Discussionmentioning

confidence: 81%

“…No correlation had been found between these thyroid doses and conditions leading to an enhanced exposure to free radioiodine, such as unbound I − in the radioantibody preparation, enhanced metabolic breakdown of the labeled antibody due to human anti‐MAb antibodies (human antimouse antibodies [HAMA], human antichimeric antibodies [HACA], or human antihuman antibodies [HAHA]), or immune complex formation with circulating antigens 21. However, a relationship between the thyroid doses and the patients' compliance in taking their cold iodide‐blocking medications was found 21. Whereas no rising thyroid‐stimulating hormone titers or other signs of (latent) hypothyroidism were seen in low‐dose therapy patients during a 2‐year follow‐up period,15, 20, 21 the considerably higher activities in this myeloablative study led to significantly higher thyroid doses, eventually causing hypothyroidism 7–9, 21…”

Section: Discussionmentioning

confidence: 99%

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High-dose myeloablative radioimmunotherapy of mantle cell non-hodgkin lymphoma with the iodine-131-labeled chimeric anti-CD20 antibody C2B8 and autologous stem cell support

Behr

Griesinger

Riggert

et al. 2002

Cancer

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BACKGROUND CD20 has been used successfully as a target molecule for conventional low‐dose, as well as high‐dose, myeloablative radioimmunotherapy (RIT) of B‐cell non‐Hodgkin lymphoma (NHL). Mantle cell lymphoma (MCL) is an especially aggressive, prognostically unfavorable subtype of B‐cell NHL, associated with an overall 5‐year survival rate of less than 20%. Recent evidence has failed to show convincing therapeutic efficacy of conventional, nonmyeloablative RIT in patients with MCL. The aim of this pilot study was to investigate whether high‐dose, myeloablative RIT with the iodine‐131 (131I)–labeled chimeric anti‐CD20 antibody C2B8 (rituximab, obtained as Mabthera from Roche Pharma, Reinach, Switzerland) is therapeutically effective in MCL patients. METHODS A total of seven patients with chemorefractory or relapsed MCL were studied in this pilot trial. All had relapsed after high‐dose chemotherapy with autologous stem cell transplantation (four of them combined with 12 grays (Gy) total‐body irradiation). A diagnostic‐dosimetric study was performed with approximately 10 mCi of 131I‐labeled C2B8 at a protein dose of 2.5 mg per kg body weight, in order to assess its biodistribution and dosimetry. If splenic pooling was observed, as is typically the case in patients with splenomegaly, the protein dose was doubled in additional studies until a “favorable” biodistribution was obtained. Therapy was performed with myeloablative doses of 261–495 mCi of 131I‐labeled C2B8 at the previously optimized protein dose, aiming at lung doses ≤ 27 Gy. Homologous stem cell support was provided. Clinical follow‐up was obtained at 3‐month intervals for up to 38 months (median observation time, 25 months). Overall, in six patients the 2.5 mg/kg protein dose was used, whereas in one patient with splenomegaly, 10 mg/kg was necessary to overcome the splenic antigenic sink. RESULTS Blood cell nadirs were reached at 2–3 weeks after therapy infusion, but all patients reengrafted at 7–10 days after stem cell reinfusion. Nonhematologic toxicity was restricted to mild‐to‐moderate nausea, fever, transient bilirubin, or liver enzyme elevations. One patient with preexisting alcoholic cirrhosis experienced a deterioration of liver function. Despite thyroid blocking, 5 of 7 patients developed hypothyroidism, requiring thyroxine substitution at 6–18 months after RIT. Six patients experienced a complete and one a good partial remission. Five patients were still in CR at the time this article was written, and six are still alive for more than 3 years; one patient relapsed locally at 3 months and one systemically at 26 months after RIT. CONCLUSIONS High‐dose myeloablative radioimmunotherapy with 131I‐labeled anti‐CD20 antibodies seems to be associated with a high response rate and moderate toxicity in patients with MCL. Further follow‐up to monitor the long‐term outcome as well as systematic prospective clinical studies are indicated. Cancer 2002;94:1363–72. © 2002 American Cancer Society. DOI 10.1002/cncr.10307

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Section: Discussionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

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High-dose myeloablative radioimmunotherapy of mantle cell non-hodgkin lymphoma with the iodine-131-labeled chimeric anti-CD20 antibody C2B8 and autologous stem cell support

Behr

Griesinger

Riggert

et al. 2002

Cancer

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“…The standard preventive procedure of oral iodine administration has been shown to reduce thyroid uptake of 131 I to <1% of the injected activity in patients receiving radioimmunotherapy with 131 I-labeled mAbs (27). Interestingly, the only patient to become biochemically hypothyroid only received 5.2 Gy to the thyroid gland-well below the mean experienced by the study population.…”

Section: Discussionmentioning

confidence: 90%

Phase I Trial of 131I-huA33 in Patients with Advanced Colorectal Carcinoma

Chong¹,

Lee²,

Hopkins³

et al. 2005

Clinical Cancer Research

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Radioimmunotherapy of small-volume disease of metastatic colorectal cancer

Behr

Liersch

Greiner-Bechert

et al. 2002

Cancer

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BACKGROUND Whereas radioimmunotherapy (RIT) has shown disappointing results in bulky, solid tumors, preclinical results in small‐volume disease and in an adjuvant setting are promising. In a previous Phase I study, the authors had encouraging results with the iodine‐131 (131I)–labeled humanized anti–carcinoembryonic antigen (anti‐CEA) antibody (MAb) hMN‐14 in small‐volume disease of colorectal cancer. The aim of this study was to evaluate, in a subsequent Phase II trial, the therapeutic efficacy of this 131I‐labeled humanized anti‐CEA antibody in colorectal cancer patients with small‐volume disease or in an adjuvant setting. METHODS Thirty colorectal cancer patients, with small‐volume metastatic disease (n = 21; all lesions ≤ 3.0 cm, and chemorefractory to 5‐fluorouracil and folinic acid) or in an adjuvant setting (n = 9), 4–6 weeks after surgical resection of liver metastases with curative intention, were studied. The patients were given a single injection of 131I‐hMN‐14 immunoglobulin G at a 60 mCi/m2 dose level, which was shown to be the maximum tolerated dose in the previous Phase I study. Follow‐up was obtained at 3‐month intervals for as long as 36 months. RESULTS At a mean blood‐based red marrow dose of 1.8 ± 0.8 Gy, myelotoxicity was the only toxicity observed, but only 1 of 28 assessable patients developed transient Grade 4 thrombocytopenia. Of the 21 patients with radiologically documented lesions, 19 were assessable. Three experienced partial remission and eight showed minor responses up to 15 months in duration (corresponding to an objective response rate of 16% and an overall response rate of 58%; the mean duration of response was 9 months). At the time this article was written, seven of nine patients in the adjuvant setting had remained free of disease for up to 36 months (one patient relapsed after 6 months and another after 30 months), whereas the relapse rate in a historical control group receiving chemotherapy was 67% over the same time period. Five patients with radiologically documented lesions, having experienced at least disease stabilization as a consequence of RIT, were retreated at the same 60‐mCi/m2 dose level at 8–16 months after the first therapy. No evidence of increased toxicity was observed (no hematologic toxicity was higher than Grade 3). Two of four assessable retreated patients experienced partial remissions; one of these four again experienced disease stabilization as a consequence of the second radioantibody therapy injection. CONCLUSIONS These data suggest that RIT is a safe and effective form of therapy for small‐volume colorectal cancer and has potential as treatment for colorectal cancer in an adjuvant setting. Toxicity is restricted to mild and transient leuko‐ and thrombocytopenia. Retreatment seems to be a feasible option. A prospective randomized comparison with standard chemotherapy is indicated. Cancer 2002;94:1373–81. © 2002 American Cancer Society. DOI 10.1002/cncr.10308

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Thyroid radiation doses during radioimmunotherapy of CEA-expressing tumours with 131I-labelled monoclonal antibodies

Cited by 7 publications

References 0 publications

High-dose myeloablative radioimmunotherapy of mantle cell non-hodgkin lymphoma with the iodine-131-labeled chimeric anti-CD20 antibody C2B8 and autologous stem cell support

High-dose myeloablative radioimmunotherapy of mantle cell non-hodgkin lymphoma with the iodine-131-labeled chimeric anti-CD20 antibody C2B8 and autologous stem cell support

Phase I Trial of 131I-huA33 in Patients with Advanced Colorectal Carcinoma

Radioimmunotherapy of small-volume disease of metastatic colorectal cancer

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