SEARCH

SEARCH BY CITATION

Keywords:

  • radioimmunotherapy;
  • paclitaxel;
  • docetaxel;
  • immunotherapy;
  • prostate cancer

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.