Combining taxanes with radiation for solid tumors

Choy, Hak

doi:10.1002/1097-0215(20000620)90:3<113::aid-ijc1>3.3.co;2-3

Cited by 1 publication

(2 citation statements)

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“…Enhancement of 177 Lu-hu3S193 anti-tumor activity with the taxane docetaxel was also explored, as docetaxel is widely used in the treatment of solid tumors such as prostate cancer, in addition to having recognized radiosensitizing properties [20,45]. Upon combination of 177 Lu-hu3S193 with docetaxel in vivo, marked enhancement of DU145 tumor radiosensitivity was observed, resulting in significantly reduced tumor volume in all mice receiving combined therapies.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to targeted molecular therapies, standard cytotoxic drugs have been investigated for their ability to enhance tumor response to radiation. These include taxanes such as docetaxel, for which the key mechanism of action involves microtubular stabilization resulting in mitotic block at the radiosensitive G2/M phase of the cell cycle [20,21]. Synergistic enhancement of radiotherapy following combination with taxanes has been observed in prostate cancer using both external beam radiotherapy and RIT [22][23][24].…”

Section: Introductionmentioning

confidence: 99%

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Therapeutic efficacy of ¹⁷⁷Lu‐CHX‐A″‐DTPA‐hu3S193 radioimmunotherapy in prostate cancer is enhanced by EGFR inhibition or docetaxel chemotherapy

Kelly

Lee

et al. 2008

The Prostate

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BACKGROUND. This study investigated the biodistribution and therapeutic efficacy of 177 Lu) radiolabeled anti-Lewis Y monoclonal antibody hu3S193 radioimmunotherapy (RIT) in mice bearing prostate cancer xenografts. The ability of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor AG1478 and docetaxel chemotherapy to enhance the efficacy of RIT was also assessed in vivo. METHODS. The in vitro cytotoxicity of 177 Lu labeled hu3S193 on Le y positive DU145 prostate cancer cells was assessed using proliferation assays, with induction of apoptosis measured by ELISA. The in vivo biodistribution and tumor localization of 177 Lu-hu3S193 was assessed in mice bearing established DU145 tumor xenografts. The efficacy and maximum tolerated dose of 177 Lu-hu3S193 RIT in vivo was determined by a dose escalation study. EGFR inhibitor AG1478 or docetaxel chemotherapy was administered at sub-therapeutic doses in conjunction with RIT in vivo. RESULTS.177 Lu-hu3S193 mediated significant induction of cytotoxicity and apoptosis in vitro. In vivo analysis of 177 Lu-hu3S193 biodistribution demonstrated specific targeting of DU145 prostate cancer xenografts, with maximal tumor uptake of 33.2 AE 3.9%ID/g observed at 120 hr post-injection. In RIT studies, 177 Lu-hu3S193 caused specific and dose-dependent inhibition of prostate cancer tumor growth. A maximum tolerated dose of 350 mCi was determined for 177 Lu-hu3S193. Combination of 177 Lu-hu3S193 RIT with EGFR inhibitor AG1478 or docetaxel chemotherapy both significantly improved efficacy. CONCLUSIONS.177 Lu-hu3S193 RIT is effective as a single agent in the treatment of Le y positive prostate cancer models. The enhancement of RIT by AG1478 or docetaxel indicates the promise of combined modality strategies.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Therapeutic efficacy of ¹⁷⁷Lu‐CHX‐A″‐DTPA‐hu3S193 radioimmunotherapy in prostate cancer is enhanced by EGFR inhibition or docetaxel chemotherapy

Kelly

Lee

et al. 2008

The Prostate

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Combining taxanes with radiation for solid tumors

Cited by 1 publication

References 43 publications

Therapeutic efficacy of ¹⁷⁷Lu‐CHX‐A″‐DTPA‐hu3S193 radioimmunotherapy in prostate cancer is enhanced by EGFR inhibition or docetaxel chemotherapy

Therapeutic efficacy of ¹⁷⁷Lu‐CHX‐A″‐DTPA‐hu3S193 radioimmunotherapy in prostate cancer is enhanced by EGFR inhibition or docetaxel chemotherapy

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Combining taxanes with radiation for solid tumors

Cited by 1 publication

References 43 publications

Therapeutic efficacy of 177Lu‐CHX‐A″‐DTPA‐hu3S193 radioimmunotherapy in prostate cancer is enhanced by EGFR inhibition or docetaxel chemotherapy

Therapeutic efficacy of 177Lu‐CHX‐A″‐DTPA‐hu3S193 radioimmunotherapy in prostate cancer is enhanced by EGFR inhibition or docetaxel chemotherapy

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Therapeutic efficacy of ¹⁷⁷Lu‐CHX‐A″‐DTPA‐hu3S193 radioimmunotherapy in prostate cancer is enhanced by EGFR inhibition or docetaxel chemotherapy

Therapeutic efficacy of ¹⁷⁷Lu‐CHX‐A″‐DTPA‐hu3S193 radioimmunotherapy in prostate cancer is enhanced by EGFR inhibition or docetaxel chemotherapy