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J Nucl Med. 2008; 49 (Supplement 1):326P
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Oncology-Basic Science: Therapy, Metrics & Intervention

Therapy, Metrics & Intervention Posters

Optimizing combination chemotherapy/BB2r targeted radiotherapy in preclinical models of breast cancer

Tammy Rold2, G. Sieckman1, J. Garrison2 and T. Hoffman1

1 Harry S Truman Memorial VA Hospital, Columbia, Missouri; 2 Internal Medicine, University of Missouri-Columbia, Columbia, Missouri

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Objectives: The objective of this study was to evaluate multi-dose Docetaxel and Capecitabine, administered alone and in combination with Bombesin receptor subtype 2 (BB2r) targeted radiotherapy (TRT) in preclinical models of breast cancer.

Methods: SCID mice (supplemented with estradiol) were inoculated with T47D (ER+) human breast cancer cells. Docetaxel and Capecitabine were administered at high (15mg/kg and 360mg/kg), medium (8mg/kg and 180mg/kg), and low (4mg/kg and 90mg/kg) dose levels, respectively, alone and in combination with Lu-177-DOTA-8-AOC-BBN(7-14)NH2 (TRT)at 40mCi/kg for three 21-day (D) cycles. The regimen for each treatment cycle was Docetaxel-D1 and D8, Capecitabine-D1-D5 and D8-D12, and TRT-D3.

Results: No statistical difference in median survival was observed between the non-treated tumor bearing control arm (100±35D) as compared to the TRT arm (87±2D). Median survival of combination Docetaxel/Capecitabine administered at low dose levels (73±35D) and medium dose levels (120±75D) showed no evidence of enhanced survival. Combination chemotherapy/TRT demonstrated linear enhancement of median survival as a function of escalating chemotherapy dosing with the low dose combination chemotherapy/TRT arm, medium dose combination chemotherapy/TRT arm and high dose combination chemotherapy/TRT arm exhibiting a median survival of 107±8D, 211±66D, and 305±24D, respectively.

Conclusions: BB2r targeted radiation therapy employing Lu-177-DOTA-8-AOC-BBN(7-14)NH2 in combination with chemotherapy demonstrated potential synergism in a pre-clinical xenograft breast cancer model. These data suggest further evaluation with expanded pre-clinical study populations and refinement of chemotherapy dosing is required to optimize chemotherapy/BB2r TRT utility.





This Article
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Right arrow Articles by Rold, T.
Right arrow Articles by Hoffman, T.
PubMed
Right arrow Articles by Rold, T.
Right arrow Articles by Hoffman, T.