Stein R, Juweid M, Zhang C H, Goldenberg D M
Garden State Cancer Center, Belleville, New Jersey 07109, USA.
Clin Cancer Res. 1999 Oct;5(10 Suppl):3199s-3206s.
We have shown previously significant antitumor effects using 90Y-MN-14 anti-CEA monoclonal antibody (MAb) for radioimmunotherapy (RAIT) of human medullary thyroid cancer (MTC) xenografts using the TT cell line. The purpose of this investigation was to determine the effect of combining chemotherapy and RAIT with 90Y-MN-14 in MTC. In particular, the toxicity and efficacy of various dose schedules of RAIT and doxorubicin were examined and compared with that at the maximum tolerated dose (MTD) of each single modality treatment. The MTD of RAIT of 105 microCi of 90Y-MN-14 was given alone and combined with 100 and 75% of the MTD of doxorubicin (60 mg/m2); and the MTD of doxorubicin was given alone and combined with 100 and 75% of the MTD of RAIT. In addition, 75% of each agent was also administered in combination. The MTD of RAIT was also evaluated in combination with 58 and 78% of the MTD of Taxol. Whereas 90Y-MN-14 (105 microCi) led to significant antitumor effects (P < 0.0001), doxorubicin at 60 mg/m2 or Taxol at 225 mg/m2 yielded only a slight tumor growth delay. The combinations of 100% of the MTD of RAIT and 75% of the MTD of doxorubicin and 100% of the MTD of doxorubicin and 75% of the MTD of RAIT were equitoxic to the MTD of RAIT alone and appear to result in improved efficacy compared with either RAIT or doxorubicin alone. For the 100% RAIT and 75% doxorubicin combination, the therapeutic efficacy was similar when doxorubicin was administered on the same day or 1 day after RAIT, but the treatment was less effective when doxorubicin was administered 2 days after RAIT (P < 0.03). Prolonged retardation of tumor progression was also observed in animals treated with the MTD of RAIT combined with 175 mg/m2 of Taxol, without increases in toxicity above that observed with RAIT alone. In conclusion, the combination of RAIT and chemotherapy appears to augment the antitumor effects of either treatment alone without a significant increase in toxicity. In addition, the timing of drug administration relative to RAIT in the combined therapy appears to be important.
我们之前已经证明，使用90Y-MN-14抗癌胚抗原单克隆抗体（MAb）对人甲状腺髓样癌（MTC）异种移植瘤进行放射免疫治疗（RAIT），以TT细胞系构建模型，具有显著的抗肿瘤作用。本研究的目的是确定在MTC中联合化疗与90Y-MN-14进行RAIT的效果。具体而言，研究并比较了RAIT和阿霉素不同剂量方案的毒性和疗效，并与每种单一治疗方式的最大耐受剂量（MTD）进行比较。单独给予90Y-MN-14 105微居里的RAIT的MTD，并分别联合阿霉素MTD的100%和75%（60mg/m2）；单独给予阿霉素的MTD，并分别联合RAIT MTD的100%和75%。此外，还将两种药物75%的剂量联合使用。还评估了RAIT的MTD与紫杉醇MTD的58%和78%联合使用的情况。虽然90Y-MN-14（105微居里）可产生显著的抗肿瘤作用（P<0.0001），但60mg/m2的阿霉素或225mg/m2的紫杉醇仅能轻微延迟肿瘤生长。RAIT的MTD与阿霉素MTD的75%联合使用以及阿霉素的MTD与RAIT MTD的75%联合使用，与单独使用RAIT的MTD毒性相当，且与单独使用RAIT或阿霉素相比，似乎疗效更佳。对于RAIT的100%与阿霉素的75%联合使用，当阿霉素在同一天或RAIT后1天给药时，治疗效果相似，但当阿霉素在RAIT后2天给药时，疗效较差（P<0.03）。在接受RAIT的MTD与175mg/m2紫杉醇联合治疗的动物中，也观察到肿瘤进展的长期延迟，且毒性未超过单独使用RAIT时观察到的毒性。总之，RAIT与化疗联合使用似乎可增强单独使用任何一种治疗的抗肿瘤作用，且毒性无显著增加。此外，联合治疗中药物给药相对于RAIT的时间似乎很重要。
Anticancer Res. 2003
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