A randomized phase II/III trial of a tumor vascular disrupting agent fosbretabulin tromethamine (CA4P) with carboplatin (C) and paclitaxel (P) in anaplastic thyroid cancer (ATC): Final survival analysis for the FACT trial.

Sosa, Julie Ann; Elisei, Rossella; Jarząb, Barbara; Bal, Chandrasekhar; Koussis, Haralabos; Gramza, Ann W.; Ben‐Yosef, Rami; Gitlitz, Barbara J.; Haugen, Bryan R.; Sm, Karandikar; Khuri, Fadlo R.; Licitra, Lisa; Remick, S. C.; Marur, Shanthi; Lu, Charles; Ondrey, Frank G.; Lu, S.; Balkissoon, Jai

doi:10.1200/jco.2011.29.15_suppl.5502

Cited by 31 publications

(23 citation statements)

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“…Combretastatin A4 phosphate (CA4P) is a leading small molecular VDA, which exerts potent and reversible depolymerizing effects on the tubulin cytoskeleton of endothelial cells of immature tumoral blood vessels [2,4]. Over the last two decades, following initial Phase I safety and pharmacokinetic studies [5,6], CA4P has been evaluated in Phase II-III clinical trials in combination with chemo-and/or molecular therapies in the setting of platinum-resistant recurrent ovarian cancer [7], nonsquamous non-small cell lung cancer [8] and anaplastic thyroid cancer [9], etc.…”

Section: Introductionmentioning

confidence: 99%

Predicting Clinical Efficacy of Vascular Disrupting Agents in Rodent Models of Primary and Secondary Liver Cancers: An Overview with Imaging-Histopathology Correlation

et al. 2020

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Vascular disrupting agents (VDAs) have entered clinical trials for over 15 years. As the leading VDA, combretastatin A4 phosphate (CA4P) has been evaluated in combination with chemotherapy and molecular targeting agents among patients with ovarian cancer, lung cancer and thyroid cancer, but still remains rarely explored in human liver cancers. To overcome tumor residues and regrowth after CA4P monotherapy, a novel dual targeting pan-anticancer theragnostic strategy, i.e., OncoCiDia, has been developed and shown promise previously in secondary liver tumor models. Animal model of primary liver cancer is time consuming to induce, but of value for more closely mimicking human liver cancers in terms of tumor angiogenesis, histopathological heterogeneity, cellular differentiation, tumor components, cancer progression and therapeutic response. Being increasingly adopted in VDA researches, multiparametric magnetic resonance imaging (MRI) provides imaging biomarkers to reflect in vivo tumor responses to drugs. In this article as a chapter of a doctoral thesis, we overview the construction and clinical relevance of primary and secondary liver cancer models in rodents. Target selection for CA4P therapy assisted by enhanced MRI using hepatobiliary contrast agents (CAs), and therapeutic efficacy evaluated by using MRI with a non-specific contrast agent, dynamic contrast enhanced (DCE) imaging, diffusion weighted imaging (DWI) are also described. We then summarize diverse responses among primary hepatocellular carcinomas (HCCs), secondary liver and pancreatic tumors to CA4P, which appeared to be related to tumor size, vascularity, and cellular differentiation. In general, imaging-histopathology correlation studies allow to conclude that CA4P tends to be more effective in secondary liver tumors and in more differentiated HCCs, but less effective in less differentiated HCCs and implanted pancreatic tumor. Notably, cirrhotic liver may be responsive to CA4P as well. All these could be instructive for future clinical trials of VDAs.

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Section: Introductionmentioning

confidence: 99%

Predicting Clinical Efficacy of Vascular Disrupting Agents in Rodent Models of Primary and Secondary Liver Cancers: An Overview with Imaging-Histopathology Correlation

et al. 2020

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“…Treatment with combretastatin A-4 (CA4), a VDA that has advanced to human clinical trials, has been reported to inhibit tumor cell invasion, migration and metastasis [11]. Despite the encouraging positive pre-clinical studies and human clinical trial results of members of this class of anticancer agents, no VDA has yet been approved by the FDA [12–16]. Clearly this provides an opportunity to expand the compound landscape available for therapy.…”

Section: Introductionmentioning

confidence: 99%

The vascular disrupting activity of OXi8006 in endothelial cells and its phosphate prodrug OXi8007 in breast tumor xenografts

et al. 2015

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This study describes the vascular disrupting ability and the mechanism of action of the indole-based tubulin-binding compound, OXi8006, and its water-soluble phosphate prodrug OXi8007. Treatment of rapidly proliferating human umbilical vein endothelial cells (HUVECs), used as a model for the tumor vasculature, with OXi8006 or OXi8007 caused potent microtubule disruption followed by extensive reorganization of the cytoskeletal network. The mechanism of action involved an increase in focal adhesion formation associated with an increase in phosphorylation of both non-muscle myosin light chain and focal adhesion kinase. These effects were dramatically diminished by an inhibitor of RhoA kinase, a downstream effector of RhoA. Cell cycle blockade at G2/M and cytotoxicity towards rapidly proliferating HUVECs were also observed. Capillary-like networks of HUVECs were disrupted by the action of both OXi8006 and OXi8007. The prodrug OXi8007 exhibited potent and rapid dose-dependent antivascular activity assessed by dynamic bioluminescence imaging (BLI) in an MDA-MB-231-luc breast cancer xenograft mouse model. By 6 hours post treatment, over 93% of the BLI signal was abolished with only a slight recovery at 24 hours. These findings were confirmed by histology. The results from this study demonstrate that OXi8007 is a potent vascular disrupting agent acting through an anti-microtubule mechanism involving RhoA.

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“…One-year survival was almost doubled with fosbretabulin, when compared to chemotherapy alone (23% versus 9%). OS was objectively longer in patients less than 60 years of age, increasing from a median of 3.1 months to 10.9 months (HR of 0.38, 95% CI: 0.16, 0.88) [46][47][48][49][50].…”

Section: Emerging Therapiesmentioning

confidence: 99%

Rapid Recurrence of Anaplastic Carcinoma: Advocacy towards Non-Surgery

Habra¹

2017

EMIJ

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DiscussionThe majority of anaplastic cancers are revealed by the rapid transformation of an old goitre: increase in volume, pain, dysphonia, dyspnea by tracheal compression and dysphagia thereafter. The nodal invasions, the repercussion on the general state, immediately sign the gravity of the situation. The cervical ultrasound is not specific but allows suspecting a malignant AbstractAnaplastic carcinoma of the thyroid (ATC) is a rare but aggressive tumor, its prognosis is dark. Most patients diagnosed with this disease are 65 years of age or older, treatment is based on the combined action of radiotherapy, chemotherapy and surgical removal when possible. We report a case of anaplastic carcinoma of the thyroid which has been thundering in postoperative surgery after total thyroidectomy, this case highlights the ineffectiveness of surgery in the reduction of tumor mass. Surely contribute to a historical recurrence and aggravate the prognosis. We will study through a review of the literature the clinical aspects and discuss the therapeutic modalities of this cancer.Keywords: Anaplastic thyroid carcinoma; Therapeutic modalities

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A randomized phase II/III trial of a tumor vascular disrupting agent fosbretabulin tromethamine (CA4P) with carboplatin (C) and paclitaxel (P) in anaplastic thyroid cancer (ATC): Final survival analysis for the FACT trial.

Cited by 31 publications

References 0 publications

Predicting Clinical Efficacy of Vascular Disrupting Agents in Rodent Models of Primary and Secondary Liver Cancers: An Overview with Imaging-Histopathology Correlation

Predicting Clinical Efficacy of Vascular Disrupting Agents in Rodent Models of Primary and Secondary Liver Cancers: An Overview with Imaging-Histopathology Correlation

The vascular disrupting activity of OXi8006 in endothelial cells and its phosphate prodrug OXi8007 in breast tumor xenografts

Rapid Recurrence of Anaplastic Carcinoma: Advocacy towards Non-Surgery

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