Denardo S J, Richman C M, Kukis D L, Shen S, Lamborn K R, Miers L A, Kroger L A, Perez E A, Denardo G L
Section of Radiodiagnosis and Therapy, University of California Davis Medical Center, Sacramento, USA.
Anticancer Res. 1998 Nov-Dec;18(6A):4011-8.
Paclitaxel (Taxol) has demonstrated synergistic enhancement of radioimmunotherapy (RIT) of breast cancer with Y-90 labeled antibody ChL6, in the xenografted mouse model. To determine the optimal sequence and timing of RIT and Taxol for a prospective clinical trial, efficacy and dosimetry in mice, and dosimetry in patients receiving RIT alone, were examined.
Mice bearing human breast cancer xenografts (HBT 3477) received i.v. Y-90-DOTA-peptide-ChL6 (260 microCi), and i.p. Taxol (300 or 600 micrograms) 72, 48, or 24 hours prior to RIT, or 6, 24, 48, or 72 hours after RIT.
Taxol after RIT resulted in cure, CR, or PR of all mice (70/70 tumors) and demonstrated greater therapeutic enhancement (p = 0.001) than Taxol before RIT. Mice receiving 600 micrograms Taxol 48 hours after RIT achieved 88% cure (7/8 tumors). In mice, 57% and 42% of the radiation dose to tumor and marrow, respectively, was delivered from 48-336 hours after RIT; in patients receiving 90Y-DOTA-peptide-ChL6, the corresponding values were 56% and 22%.
Taxol given approximately 48 hours after RIT provides coincident peak deposition of Taxol and Y-90 in tumor, and no Taxol in the marrow during the major radiation dose to marrow, resulting in therapeutic enhancement without observable additive toxicity. A clinical trial of low dose Taxol given after RIT to patients with metastatic breast cancer is planned.
在异种移植小鼠模型中，紫杉醇（泰素）已证明可与钇 - 90标记的抗体ChL6协同增强乳腺癌的放射免疫治疗（RIT）。为了确定RIT和紫杉醇用于前瞻性临床试验的最佳顺序和时机，研究了小鼠的疗效和剂量测定，以及单独接受RIT的患者的剂量测定。
携带人乳腺癌异种移植瘤（HBT 3477）的小鼠在RIT前72、48或24小时，或RIT后6、24、48或72小时接受静脉注射钇 - 90 - DOTA - 肽 - ChL6（260微居里）和腹腔注射紫杉醇（300或600微克）。
RIT后给予紫杉醇使所有小鼠（70/70个肿瘤）治愈、完全缓解或部分缓解，并且显示出比RIT前给予紫杉醇更大的治疗增强效果（p = 0.001）。RIT后48小时接受600微克紫杉醇的小鼠实现了88%的治愈率（7/8个肿瘤）。在小鼠中，分别有57%和42%的肿瘤和骨髓辐射剂量在RIT后48 - 336小时传递；在接受90Y - DOTA - 肽 - ChL6的患者中，相应的值分别为56%和22%。
RIT后约48小时给予紫杉醇可使紫杉醇和钇 - 90在肿瘤中同时达到峰值沉积，并且在对骨髓的主要辐射剂量期间骨髓中没有紫杉醇，从而在无明显附加毒性的情况下实现治疗增强。计划对转移性乳腺癌患者在RIT后给予低剂量紫杉醇进行临床试验。
