Anti‐tumor effect of combination therapy with intratumoral controlled‐release paclitaxel (PACLIMER® microspheres) and radiation

Lapidus, Rena G.; Dang, Wenbin; Rosen, David; Gady, Alyssa M.; Zabelinka, Yelena; O’Meally, Robert N.; DeWeese, Theodore L.; Denmeade, Samuel R.

doi:10.1002/pros.10331

Cited by 28 publications

(20 citation statements)

References 19 publications

(26 reference statements)

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“…Treatment of the xenografts with intratumoral Paclimer® alone significantly decreased tumor size compared to controls, and showed synergistic activity when combined with radiation therapy (35). This effect has also been observed by our group in intracranial 9L gliosarcomas in rats using a combination of Paclimer® and radiation therapy (36).…”

Section: Discussionsupporting

confidence: 79%

“…Paclimer® has also demonstrated beneficial effects against human prostate tumors implanted in nude mice (35). Treatment of the xenografts with intratumoral Paclimer® alone significantly decreased tumor size compared to controls, and showed synergistic activity when combined with radiation therapy (35).…”

Section: Discussionmentioning

confidence: 99%

“…This effect has also been observed by our group in intracranial 9L gliosarcomas in rats using a combination of Paclimer® and radiation therapy (36). This effect appears to be related to the radiosensitizing properties of paclitaxel (20,37), which depends on stabilization of tubulin formation that creates a block in the G2-M phase of the cell cycle (the most radiosensitive phases) (35).…”

Section: Discussionmentioning

confidence: 99%

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Local Intracerebral Administration of Paclitaxel with the Paclimer® Delivery System: Toxicity Study in a Canine Model

et al. 2005

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Introduction: Paclitaxel, a microtubule binding agent with potent anti-glioma activity in vitro, exhibits poor penetrance to the CNS when delivered systemically. To minimize toxicity and reach therapeutic concentrations in the CNS, paclitaxel was previously incorporated into biodegradable microspheres (Paclimer®), and the efficacy of Paclimer® was determined in a rat model of malignant glioma. In this study we report the safety of intracranial Paclimer® in a canine dose escalation toxicity study to prepare its translation into clinical scenarios.

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Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Local Intracerebral Administration of Paclitaxel with the Paclimer® Delivery System: Toxicity Study in a Canine Model

et al. 2005

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“…Paclitaxel is one of a few chemotherapeutic agents that is effective in patients with advanced prostate cancer (14,15). Studies using prostate-specific antigen response as an end point showed the efficacy of paclitaxel in the treatment of metastatic prostate cancer (16 -18).…”

mentioning

confidence: 99%

“…Treatment of patients with paclitaxel alone or in combination with estramustine resulted in a >50% decrease in serum prostate-specific antigen in 40% to 60% of the treated patients (16 -18). Unfortunately, patients treated with paclitaxel or other chemotherapeutic drugs experience significant systemic side effects that include neutropenia, mucositis, neurotoxicity, and gastrointestinal effects (15,17,18). These adverse effects severely limit the duration and dose of drug treatment that can be administered (14,18).…”

mentioning

confidence: 99%

Effects of 12-O-Tetradecanoylphorbol-13-acetate (TPA) in Combination with Paclitaxel (Taxol) on Prostate Cancer LNCaP Cells Cultured In vitro or Grown as Xenograft Tumors in Immunodeficient Mice

Zheng¹,

Chang²,

Cui³

et al. 2006

Clinical Cancer Research

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Purpose: To investigate the effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) in combination with paclitaxel (Taxol) on prostate cancer cells cultured in vitro or grown as tumors in immunodeficient mice. Experimental Design: Human prostate cancer LNCaP cells in culture were treated with TPA alone or in combination with paclitaxel. NCr immunodeficient mice with well-established LNCaP tumors received i.p. injections with vehicle or with TPA, paclitaxel, or TPA in combination with paclitaxel. The animals either received daily treatment for 5 consecutive days followed by a 2-day intermission, which was repeated for a total of 28 days (experiment 1), or continuous daily treatment for 28 days (experiment 2).

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Effect of Docetaxel on the Surgical Tumor Microenvironment of Head and Neck Cancer in Murine Models

Yoo

Subramanian²,

Piechocki³

et al. 2008

Arch Otolaryngol Head Neck Surg

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To identify the antitumor activity and wound-healing effect of docetaxel delivered in the surgical tumor microenvironment of head and neck squamous cell carcinoma (HNSCC).Design: Control and experimental series.Setting: Academic medical center.Subjects: BALB/c and severe combined immunodeficiency mice.Intervention: Intrawound (IW) docetaxel therapy was tested in 3 HNSCC xenograft and 2 taxane-resistant models. Intratumoral (IT) docetaxel therapy was further tested in the 2 taxane-resistant models.Main Outcome Measures: Tumor size, survival, and wound toxic effects were measured. The effect of docetaxel on various factors involved in wound healing and tumor growth within the surgical tumor microenvironment was also analyzed.Results: In a pilot study using BALB/c mice, IW docetaxel therapy was not associated with problems in wound healing. Using the HN6, HN12, and HN30 HNSCC xenograft model, IW docetaxel prevented tumor growth and improved survival when compared with controls. No local or systemic toxic effect or wound-healing problem was noted. Using taxane-resistant xenograft lung cancer (H460/ T800) and syngeneic salivary cancer (BALB/c mucoepidermoid carcinoma) models, IW therapy did not delay tumor growth. An antitumor effect was detected with repeated docetaxel injections in the H460/T800 taxane-resistant model but not in the BALB/c mucoepidermoid carcinoma model. Docetaxel inhibited the expression of growth factors and receptors in tumor cells; however, it did not inhibit the level of wound-healing growth factors in the surgical tumor microenvironment.Conclusions: These preclinical results support further testing of IW docetaxel treatment in HNSCC. Docetaxel appears to exert antitumor activity without affecting factors involved in wound healing in the tumor microenvironment.

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Anti‐tumor effect of combination therapy with intratumoral controlled‐release paclitaxel (PACLIMER® microspheres) and radiation

Abstract: 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.

Cited by 28 publications

References 19 publications

Local Intracerebral Administration of Paclitaxel with the Paclimer® Delivery System: Toxicity Study in a Canine Model

Local Intracerebral Administration of Paclitaxel with the Paclimer® Delivery System: Toxicity Study in a Canine Model

Effects of 12-O-Tetradecanoylphorbol-13-acetate (TPA) in Combination with Paclitaxel (Taxol) on Prostate Cancer LNCaP Cells Cultured In vitro or Grown as Xenograft Tumors in Immunodeficient Mice

Effect of Docetaxel on the Surgical Tumor Microenvironment of Head and Neck Cancer in Murine Models

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