Combined modality radioimmunotherapy for human prostate cancer xenografts with taxanes and 90Yttrium-DOTA-peptide-ChL6

Robert T O'Donnell, Sally J. Denardo, Laird A. Miers, Kathleen R. Lamborn, David L. Kukis, Gerald L Denardo, Frederick J Meyers

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)27-37
Number of pages11
JournalProstate
Volume50
Issue number1
DOIs
StatePublished - Jan 1 2002

Fingerprint

docetaxel
Radioimmunotherapy
Taxoids
Heterografts
Prostatic Neoplasms
Paclitaxel
Peptides
Nude Mice
Neoplasms
ChL6 monoclonal antibody
Tumor Burden
Pharmacokinetics
Radiation

Keywords

  • Docetaxel
  • Immunotherapy
  • Paclitaxel
  • Prostate cancer
  • Radioimmunotherapy

ASJC Scopus subject areas

  • Urology

Cite this

Combined modality radioimmunotherapy for human prostate cancer xenografts with taxanes and 90Yttrium-DOTA-peptide-ChL6. / O'Donnell, Robert T; Denardo, Sally J.; Miers, Laird A.; Lamborn, Kathleen R.; Kukis, David L.; Denardo, Gerald L; Meyers, Frederick J.

In: Prostate, Vol. 50, No. 1, 01.01.2002, p. 27-37.

Research output: Contribution to journalArticle

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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.",
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T1 - Combined modality radioimmunotherapy for human prostate cancer xenografts with taxanes and 90Yttrium-DOTA-peptide-ChL6

AU - O'Donnell, Robert T

AU - Denardo, Sally J.

AU - Miers, Laird A.

AU - Lamborn, Kathleen R.

AU - Kukis, David L.

AU - Denardo, Gerald L

AU - Meyers, Frederick J

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N2 - 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.

AB - 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.

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