Anti-Tumor Effect of Combination Therapy with Intratumoral Controlled-Release Paclitaxel (PACLIMER®Microspheres) and Radiation

Rena G. Lapidus, Wenbin Dang, David Marc Rosen, Alyssa M. Gady, Yelena Zabelinka, Robert O'Meally, Theodore DeWeese, Samuel R Denmeade

Research output: Contribution to journalArticle

Abstract

BACKGROUND. Paclitaxel is one of the few chemotherapeutics effective in patients with advanced protstate cancer. Paclitaxel has also been reported to have radiosensitizing effects in prostate cancer. Local delivery of a controlled-release paclitaxel product may allow for increase local concentrations of paclitaxel at the tumor site and, in conjunction with radiation, may enhance cell kill by its radiosensitization mechanism. METHODS. Orthotopic LNCaP tumors were injected with 40% PACLIMER® Microspheres (40% loading; w:w) when tumors were 100-200 mm3. Twenty-eight days post cell injection, mice were sacrificed, tumors weighed, and serum measured for PSA. TSU-xenografts were injected with PACLIMER Microspheres (10% and 40% loaded; w:w) or placebo microspheres when the tumors were approximately 100 mm3. Half of xenograft tumors were irradiated with a single dose (10 Gy) of radiation. Tumor volume was followed over time. RESULTS. Forty percent PACLIMER Microspheres significantly reduced tumor growth in the LNCaP orthotopic model. PSA was a good indicator of response. Forty percent PACLIMER Microspheres had a significant effect on slowing TSU growth compared to placebo microspheres. Addition of a single acute dose of radiation significantly enhanced the effect of 10% PACLIMER Microspheres (P <0.05), had minimal effect on 40% PACLIMER Microspheres, and no enhancing effect on tumors treated with placebo microspheres. CONCLUSIONS. A controlled-release formulation of paclitaxel can be very effective in the treatment of prostate cancer. Additionally, PACLIMER Microspheres may be effectively used as a radiosensitizer in genitourinary cancers.

Original languageEnglish (US)
Pages (from-to)291-298
Number of pages8
JournalProstate
Volume58
Issue number3
DOIs
StatePublished - Feb 15 2004

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Paclitaxel
Microspheres
Radiation
Neoplasms
Therapeutics
Placebos
Heterografts
Prostatic Neoplasms
Urogenital Neoplasms
Radiation-Sensitizing Agents
Radiation Dosage
Growth
Tumor Burden
Injections

Keywords

  • LNCaP
  • Orthotopic
  • Radiosensitizer
  • Tsu PR1

ASJC Scopus subject areas

  • Urology

Cite this

Anti-Tumor Effect of Combination Therapy with Intratumoral Controlled-Release Paclitaxel (PACLIMER®Microspheres) and Radiation. / Lapidus, Rena G.; Dang, Wenbin; Rosen, David Marc; Gady, Alyssa M.; Zabelinka, Yelena; O'Meally, Robert; DeWeese, Theodore; Denmeade, Samuel R.

In: Prostate, Vol. 58, No. 3, 15.02.2004, p. 291-298.

Research output: Contribution to journalArticle

Lapidus, Rena G. ; Dang, Wenbin ; Rosen, David Marc ; Gady, Alyssa M. ; Zabelinka, Yelena ; O'Meally, Robert ; DeWeese, Theodore ; Denmeade, Samuel R. / Anti-Tumor Effect of Combination Therapy with Intratumoral Controlled-Release Paclitaxel (PACLIMER®Microspheres) and Radiation. In: Prostate. 2004 ; Vol. 58, No. 3. pp. 291-298.
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abstract = "BACKGROUND. Paclitaxel is one of the few chemotherapeutics effective in patients with advanced protstate cancer. Paclitaxel has also been reported to have radiosensitizing effects in prostate cancer. Local delivery of a controlled-release paclitaxel product may allow for increase local concentrations of paclitaxel at the tumor site and, in conjunction with radiation, may enhance cell kill by its radiosensitization mechanism. METHODS. Orthotopic LNCaP tumors were injected with 40{\%} PACLIMER{\circledR} Microspheres (40{\%} loading; w:w) when tumors were 100-200 mm3. Twenty-eight days post cell injection, mice were sacrificed, tumors weighed, and serum measured for PSA. TSU-xenografts were injected with PACLIMER Microspheres (10{\%} and 40{\%} loaded; w:w) or placebo microspheres when the tumors were approximately 100 mm3. Half of xenograft tumors were irradiated with a single dose (10 Gy) of radiation. Tumor volume was followed over time. RESULTS. Forty percent PACLIMER Microspheres significantly reduced tumor growth in the LNCaP orthotopic model. PSA was a good indicator of response. Forty percent PACLIMER Microspheres had a significant effect on slowing TSU growth compared to placebo microspheres. Addition of a single acute dose of radiation significantly enhanced the effect of 10{\%} PACLIMER Microspheres (P <0.05), had minimal effect on 40{\%} PACLIMER Microspheres, and no enhancing effect on tumors treated with placebo microspheres. CONCLUSIONS. A controlled-release formulation of paclitaxel can be very effective in the treatment of prostate cancer. Additionally, PACLIMER Microspheres may be effectively used as a radiosensitizer in genitourinary cancers.",
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T1 - Anti-Tumor Effect of Combination Therapy with Intratumoral Controlled-Release Paclitaxel (PACLIMER®Microspheres) and Radiation

AU - Lapidus, Rena G.

AU - Dang, Wenbin

AU - Rosen, David Marc

AU - Gady, Alyssa M.

AU - Zabelinka, Yelena

AU - O'Meally, Robert

AU - DeWeese, Theodore

AU - Denmeade, Samuel R

PY - 2004/2/15

Y1 - 2004/2/15

N2 - BACKGROUND. Paclitaxel is one of the few chemotherapeutics effective in patients with advanced protstate cancer. Paclitaxel has also been reported to have radiosensitizing effects in prostate cancer. Local delivery of a controlled-release paclitaxel product may allow for increase local concentrations of paclitaxel at the tumor site and, in conjunction with radiation, may enhance cell kill by its radiosensitization mechanism. METHODS. Orthotopic LNCaP tumors were injected with 40% PACLIMER® Microspheres (40% loading; w:w) when tumors were 100-200 mm3. Twenty-eight days post cell injection, mice were sacrificed, tumors weighed, and serum measured for PSA. TSU-xenografts were injected with PACLIMER Microspheres (10% and 40% loaded; w:w) or placebo microspheres when the tumors were approximately 100 mm3. Half of xenograft tumors were irradiated with a single dose (10 Gy) of radiation. Tumor volume was followed over time. RESULTS. Forty percent PACLIMER Microspheres significantly reduced tumor growth in the LNCaP orthotopic model. PSA was a good indicator of response. Forty percent PACLIMER Microspheres had a significant effect on slowing TSU growth compared to placebo microspheres. Addition of a single acute dose of radiation significantly enhanced the effect of 10% PACLIMER Microspheres (P <0.05), had minimal effect on 40% PACLIMER Microspheres, and no enhancing effect on tumors treated with placebo microspheres. CONCLUSIONS. A controlled-release formulation of paclitaxel can be very effective in the treatment of prostate cancer. Additionally, PACLIMER Microspheres may be effectively used as a radiosensitizer in genitourinary cancers.

AB - BACKGROUND. Paclitaxel is one of the few chemotherapeutics effective in patients with advanced protstate cancer. Paclitaxel has also been reported to have radiosensitizing effects in prostate cancer. Local delivery of a controlled-release paclitaxel product may allow for increase local concentrations of paclitaxel at the tumor site and, in conjunction with radiation, may enhance cell kill by its radiosensitization mechanism. METHODS. Orthotopic LNCaP tumors were injected with 40% PACLIMER® Microspheres (40% loading; w:w) when tumors were 100-200 mm3. Twenty-eight days post cell injection, mice were sacrificed, tumors weighed, and serum measured for PSA. TSU-xenografts were injected with PACLIMER Microspheres (10% and 40% loaded; w:w) or placebo microspheres when the tumors were approximately 100 mm3. Half of xenograft tumors were irradiated with a single dose (10 Gy) of radiation. Tumor volume was followed over time. RESULTS. Forty percent PACLIMER Microspheres significantly reduced tumor growth in the LNCaP orthotopic model. PSA was a good indicator of response. Forty percent PACLIMER Microspheres had a significant effect on slowing TSU growth compared to placebo microspheres. Addition of a single acute dose of radiation significantly enhanced the effect of 10% PACLIMER Microspheres (P <0.05), had minimal effect on 40% PACLIMER Microspheres, and no enhancing effect on tumors treated with placebo microspheres. CONCLUSIONS. A controlled-release formulation of paclitaxel can be very effective in the treatment of prostate cancer. Additionally, PACLIMER Microspheres may be effectively used as a radiosensitizer in genitourinary cancers.

KW - LNCaP

KW - Orthotopic

KW - Radiosensitizer

KW - Tsu PR1

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DO - 10.1002/pros.10331

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