Synergistic therapy of breast cancer with Y-90-chimeric L6 and paclitaxel in the xenografted mouse model: Development of a clinical protocol

Background. 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 timin g of RIT and Taxol for a prospective clinical trial efficacy and dosimetry in mice, and dosimetry in patients receiving RIT alone, were examined. Mate rials and Methods. Mice bearing human breast cancer xenografts (HBT 3477) r eceived iv Y-90-DOTA-peptide-ChL6 (260 mu Ci), and i.p. Taxol (300 or 600 m u g) 72, 48, or 24 hours prior to RIT, or 6, 24, 48, or 72 hours after RIT. Results. Taxol after RIT resulted in cure, CR or PR of all mice (70/70 tum ors) and demonstrated greater therapeutic enhancement (p = 0.001) than Taxo l before RIT. Mice receiving 600 mu g 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 Y-90-DOTA-peptide-ChL6, the corresponding values were 56% and 22 %. Conclusions. Taxol given approximately 48 hours after RIT provides coinc ident peak deposition of Taxol and Y-90 in tumor; and no Taxol in the marro w during the major radiation dose to marrow, resulting in therapeutic enhan cement without observable additive toxicity A clinical trial of low dose Ta xol given after RIT to patients with metastatic breast cancer is planned.