Combined modality radioimmunotherapy for human prostate cancer xenografts with taxanes and 90yttrium-DOTA-peptide-ChL6
Article first published online: 14 DEC 2001
Copyright © 2002 Wiley-Liss, Inc.
Volume 50, Issue 1, pages 27–37, 1 January 2002
How to Cite
O'Donnell, R. T., DeNardo, S. J., Miers, L. A., Lamborn, K. R., Kukis, D. L., DeNardo, G. L. and Meyers, F. J. (2002), Combined modality radioimmunotherapy for human prostate cancer xenografts with taxanes and 90yttrium-DOTA-peptide-ChL6. Prostate, 50: 27–37. doi: 10.1002/pros.10029
- Issue published online: 21 DEC 2001
- Article first published online: 14 DEC 2001
- Manuscript Accepted: 10 SEP 2001
- Manuscript Received: 30 JUN 2001
- NCI. Grant Number: PO1-CA47829
- Cancer Research Institute, New York, NY. Grant Number: 57310
- prostate cancer
Therapy for prostate cancer in the PC3 tumor-nude mouse model with 90yttrium-(90Y)-DOTA-peptide-ChL6 (5.55 MBq;150 μCi) has resulted in durable responses. To make radioimmunotherapy (RIT) more effective, the radiation-enhancing drugs Taxol (paclitaxel) and Taxotere (docetaxel) were tested for synergy with 90Y-DOTA-peptide-ChL6.
Nude mice bearing human prostate cancer PC3 xenografts were treated with 90Y-DOTA-peptide-ChL6 (2.78 MBq; 75 μCi) and after 24 hr, paclitaxel (300 or 600 μg), or docetaxel (300 μg). Tumor size, survival, blood counts, and pharmacokinetics were monitored to assess efficacy and toxicity.
Docetaxel plus RIT had a 67% cure rate, whereas no mice were cured among the RIT alone, chemotherapy alone, or untreated controls. Paclitaxel (600 μg) plus RIT produced a 100% response rate with 20% cures. Average tumor volume was reduced to a greater degree in the combined modality radioimmunotherapy (CMRIT) groups compared to controls and the anti-tumor response was durable. Myelotoxicity in the combined modality groups (RIT plus paclitaxel or RIT plus docetaxel) were similar to groups receiving the same dose of RIT alone.
In the PC3-tumor nude mouse model, addition of paclitaxel or docetaxel to 90Y-DOTA-peptide-ChL6, in doses clinically achievable in humans, provided therapeutic synergy without increased or excessive toxicity. Prostate 50: 27–37, 2002. © 2002 Wiley-Liss, Inc.