This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kraeber-Bodéré, F. Articles by Thédrez, P. Search for Related Content PubMed PubMed Citation Articles by Kraeber-Bodéré, F. Articles by Thédrez, P.

Institut National de la Santé et de la Recherche Médicale Research Unit 463, CEA L. R. C. 18V and Regional Cancer Center, 44093 Nantes, Cedex 01, France

A significant antitumor effect associated with moderate toxicity was obtained previously with anticarcinoembryonic antigen x antidiethylene- triaminepentaacetic acid (DTPA)-indium F6-734 bispecific antibody and iodine-131-labeled DTPA-indium bivalent hapten in an animal model of medullary thyroid cancer (MTC). The purpose of this study was to determine whether the cytotoxic agents doxorubicin and paclitaxel, also known as radiosensitizers, improve efficacy of pretargeted radioimmunotherapy (RIT) in experimental MTC. Nude mice bearing TT MTC xenograft were treated with F6-734 and iodine-131-labeled DTPA-indium bivalent hapten injected 48 h apart with or without doxorubicin or paclitaxel. The maximum tolerated dose (MTD) of RIT was 92.5 MBq (as determined previously) and that of doxorubicin and paclitaxel 200 and 1000 µg, respectively. A control group received no treatment. Animal weight, hematotoxicity, tumor volume, and serum calcitonin were monitored for 5 months. Tumor growth inhibition induced by drugs alone, RIT alone, or combined therapy was characterized by measuring relative tumor volume 20, 40, and 60 days after treatment to detect additivity or synergism. Mean tumor volume doubling time (MTVDT) was 13 ± 4 days in the control group, 15 ± 8 days in the group treated with the MTD of doxorubicin, and 32 ± 13 days in the group treated with the MTD of paclitaxel. After RIT alone at 92.5 MBq, MTVDT was 86 ± 22 days. After RIT at 74 MBq (80% of MTD), MTVDT was 56 ± 10 days. MTVDT was not significantly different from this value after RIT plus doxorubicin, 60 ± 16 days (65 and 100% of the respective single-agent MTDs). Combination of RIT with paclitaxel (65 and 100% of the respective single-agent MTDs) prolonged the suppression of tumor growth. One complete response was observed, and MTVDT was 114 ± 44 days. This value was significantly longer than the value obtained with RIT alone at 74 MBq (P < 0.05) or with RIT combined with doxorubicin (P < 0.02). The change in serum calcitonin levels paralleled those in tumor volume. Analysis of dose-response curves at days 20 and 40 showed additivity between RIT and paclitaxel, and analysis at day 60 suggested a synergistic effect. In conclusion, addition of doxorubicin did not improve RIT efficacy, whereas paclitaxel improved RIT efficacy significantly without increasing toxicity.

This article has been cited by other articles:

				S. M. Azouz, J. Walpole, S. Amirifeli, K. N. Taylor, M. W. Grinstaff, and Y. L. Colson Prevention of local tumor growth with paclitaxel-loaded microspheres. J. Thorac. Cardiovasc. Surg., May 1, 2008; 135(5): 1014 - 1021. [Abstract] [Full Text] [PDF]

				K. A. B. Knostman, S. M. Jhiang, and C. C. Capen Genetic Alterations in Thyroid Cancer: The Role of Mouse Models Vet. Pathol., January 1, 2007; 44(1): 1 - 14. [Abstract] [Full Text] [PDF]

				D. Moosmayer, D. Berndorff, C.-H. Chang, R. M. Sharkey, A. Rother, S. Borkowski, E. A. Rossi, W. J. McBride, T. M. Cardillo, D. M. Goldenberg, et al. Bispecific antibody pretargeting of tumor neovasculature for improved systemic radiotherapy of solid tumors. Clin. Cancer Res., September 15, 2006; 12(18): 5587 - 5595. [Abstract] [Full Text] [PDF]

				R. M. Sharkey and D. M. Goldenberg Targeted Therapy of Cancer: New Prospects for Antibodies and Immunoconjugates CA Cancer J Clin, July 1, 2006; 56(4): 226 - 243. [Abstract] [Full Text] [PDF]

				D. M. Goldenberg, R. M. Sharkey, G. Paganelli, J. Barbet, and J.-F. Chatal Antibody Pretargeting Advances Cancer Radioimmunodetection and Radioimmunotherapy J. Clin. Oncol., February 10, 2006; 24(5): 823 - 834. [Abstract] [Full Text] [PDF]

				F. Kraeber-Bodere, C. Rousseau, C. Bodet-Milin, L. Ferrer, A. Faivre-Chauvet, L. Campion, J.-P. Vuillez, A. Devillers, C.-H. Chang, D. M. Goldenberg, et al. Targeting, Toxicity, and Efficacy of 2-Step, Pretargeted Radioimmunotherapy Using a Chimeric Bispecific Antibody and 131I-Labeled Bivalent Hapten in a Phase I Optimization Clinical Trial J. Nucl. Med., February 1, 2006; 47(2): 247 - 255. [Abstract] [Full Text] [PDF]

				C. J. Strock, J.-I. Park, D. M. Rosen, B. Ruggeri, S. R. Denmeade, D. W. Ball, and B. D. Nelkin Activity of Irinotecan and the Tyrosine Kinase Inhibitor CEP-751 in Medullary Thyroid Cancer J. Clin. Endocrinol. Metab., January 1, 2006; 91(1): 79 - 84. [Abstract] [Full Text] [PDF]

				J. Barbet, L. Campion, F. Kraeber-Bodere, J.-F. Chatal, and and the GTE Study Group Prognostic Impact of Serum Calcitonin and Carcinoembryonic Antigen Doubling-Times in Patients with Medullary Thyroid Carcinoma J. Clin. Endocrinol. Metab., November 1, 2005; 90(11): 6077 - 6084. [Abstract] [Full Text] [PDF]

				H. Karacay, P.-Y. Brard, R. M. Sharkey, C.-H. Chang, E. A. Rossi, W. J. McBride, D. R. Ragland, I. D. Horak, and D. M. Goldenberg Therapeutic Advantage of Pretargeted Radioimmunotherapy Using a Recombinant Bispecific Antibody in a Human Colon Cancer Xenograft Clin. Cancer Res., November 1, 2005; 11(21): 7879 - 7885. [Abstract] [Full Text] [PDF]

				R. M. Sharkey, H. Karacay, T. M. Cardillo, C.-H. Chang, W. J. McBride, E. A. Rossi, I. D. Horak, and D. M. Goldenberg Improving the Delivery of Radionuclides for Imaging and Therapy of Cancer Using Pretargeting Methods Clin. Cancer Res., October 1, 2005; 11(19): 7109s - 7121s. [Abstract] [Full Text] [PDF]

				R. M. Sharkey and D. M. Goldenberg Perspectives on Cancer Therapy with Radiolabeled Monoclonal Antibodies J. Nucl. Med., January 1, 2005; 46(1_suppl): 115S - 127S. [Abstract] [Full Text] [PDF]

				R. Stein and D. M. Goldenberg A humanized monoclonal antibody to carcinoembryonic antigen, labetuzumab, inhibits tumor growth and sensitizes human medullary thyroid cancer xenografts to dacarbazine chemotherapy Mol. Cancer Ther., December 1, 2004; 3(12): 1559 - 1564. [Abstract] [Full Text] [PDF]

				C.-H. Chang, R. M. Sharkey, E. A. Rossi, H. Karacay, W. McBride, H. J. Hansen, J.-F. Chatal, J. Barbet, and D. M. Goldenberg Molecular Advances in Pretargeting Radioimunotherapy with Bispecific Antibodies Mol. Cancer Ther., May 1, 2002; 1(7): 553 - 563. [Abstract] [Full Text] [PDF]