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A Phase I Trial Combining High-Dose ⁹⁰Y-Labeled Humanized Anti-CEA Monoclonal Antibody with Doxorubicin and Peripheral Blood Stem Cell Rescue in Advanced Medullary Thyroid Cancer

¹ Center for Molecular Medicine and Immunology, Garden State Cancer Center, Belleville, New Jersey
² St. Joseph’s Hospital and Medical Center, Paterson, New Jersey

View larger version (25K): [in a new window]   FIGURE 1. Treatment plan. Each patient received a pretherapy imaging study with 111In-hMN-14 IgG. This study was used to (a) confirm targeting of at least 1 index lesion, (b) estimate radiation-absorbed doses for 90Y-hMN-14 to ensure that the dose to liver would not exceed 3,000 cGy and the lung and kidney dose would not exceed 2,000 cGy at prescribed 90Y-hMN-14 administered dose, and (c) to verify that amount of 90Y radioactivity remaining in the whole body would be 3 mCi/m2 no later than 14 d in order to reinfuse PBSCs within this time. PBSCs were reinfused between 7 and 12 d, depending on dose level. G-CSF = granulocyte colony-stimulating factor; Mab = monoclonal antibody

View larger version (16K): [in a new window]   FIGURE 2. Impact of plasma CEA on blood pharmacokinetic behavior of 90Y-hMN-14 IgG (observed) and that predicted for 90Y-hMN-14 IgG from 111In-hMN-14 IgG injection given 1 wk earlier (predicted).

View larger version (13K): [in a new window]   FIGURE 3. Frequency distribution shows number of patients for whom radiation-absorbed dose to red marrow (RM) by imaging was calculated to be lower (negative) or higher (positive) than dose derived from blood clearance data. Determination of RM dose by external scintigraphy was possible in 12 of 14 patients given 90Y-hMN-14. Data from a 16-y-old subject were also not included in this analysis of adult patients. In this subject, dose derived from imaging study was 52.5% less than that derived from blood clearance data.

View larger version (46K): [in a new window]   FIGURE 4. Anterior and posterior WB images of patient 1831 shows biodistribution of first injection of 111In-hMN-14 IgG (top) and 111In-hMN-14 IgG given with 90Y-hMN-14 IgG injection 1 wk later (bottom).

View larger version (9K): [in a new window]   FIGURE 5. Potential factors contributing to radiation-absorbed dose to liver. RT-E = residence time, effective.

View larger version (12K): [in a new window]   FIGURE 6. Tumor dosimetry shows distribution of radiation-absorbed dose delivered either on a per MBq basis (A) or total dose (B) based on size of tumor. B also lists total dose in each of 8 patients (4-digit patient numbers) and number of lesions per patient in parentheses.

View larger version (102K): [in a new window]   FIGURE 7. Patient 1853, a 41-y-old man, presented with widely metastatic MTC in neck, chest, and liver and was treated at a dose of 1,850 MBq/m2 with 90Y-hMN-14 IgG + 60 mg/m2 Dox 1 d later. Two index lesions selected in baseline CT images were in liver. (A and B) Sequential slices that show 1 index lesion as an irregularly shaped tumor in upper portion of left lobe of liver. (C and D) Two slices though lower portion of liver show another very large laterally positioned lesion that was apparent in 11 consecutive 7.0-mm slices. Extent of this lateral lesion can be better appreciated in nuclear images to the right, where its size was estimated to be 234 g. Regions are drawn around baseline lesions, since several tumors were poorly enhanced. Three-month CT scan shows considerable reduction in upper lesion with noticeable reduction and more necrosis in lateral lesion. WB and anterior planar nuclear images (E and G, respectively) taken 6 d after 111In-hMN-14 IgG show very high accretion of radioactivity in lateral liver lesion as well as uptake in several other locations throughout liver. (H) Transaxial SPECT view of liver at 48 h also shows intense uptake in lateral lesion. (F) Antibody targeting of what proved to be 5 separate lesions in neck, with a sum of the product of their perpendicular diameters at baseline equaling 9.64 cm2, decreasing to a sum of 3.28 cm2 at 3 mo (66% reduction).