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Acute Toxicity Oral
The Experts below are selected from a list of 42 Experts worldwide ranked by ideXlab platform
Eric Deutsch – One of the best experts on this subject based on the ideXlab platform.
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Normal tissues toxicities triggered by combined anti-angiogenic and radiation therapies: hurdles might be ahead
British journal of cancer, 2012Co-Authors: Monica Mangoni, Marie-catherine Vozenin, Giampaolo Biti, Eric DeutschAbstract:Drugs developed to inhibit angiogenesis have now entered routine clinical practice in anticancer therapies. However, in most cases no permanent tumour control can be achieved, therefore the combination of anti-angiogenic strategies with cytotoxic agents such as chemotherapy, ionising radiation, or both represents a promising approach to increase cure rate of solid tumours (Koukourakis, 2001; Jain, 2005). Unfortunately angiogenesis is not tumour restricted but is also found in many other physiological and pathological conditions, for example, normal growth, wound healing and inflammation (Carmeliet and Jain, 2000) hence, inhibition of angiogenesis combined with other treatment may increase normal tissue Toxicity. US Food and Drug Administration has published a warning regarding the use of the anti-angiogenic agent bevacizumab (Avastin) in combination with chest radiotherapy (http://www.fda.gov/medwaTCH/safety/2007/Avastin_DHCP_TEF_Final8April2007.pdf) and several publications now report serious adverse events especially after treatment of thorax, gastrointestinal tract, head and neck and brain malignancies combining bevacizumab and radiotherapy (Willett et al, 2005; Crane et al, 2006; Carden et al, 2008; Seiwert et al, 2008; Gutin et al, 2009; Spigel et al, 2010; Lai et al, 2011). Most of these studies aimed at evaluating the anti-tumour efficacy of combined bevacizumab concurrently with radiotherapy in poor outcome situations however the results obtained indicate the need for caution in the development of bevacizumab and related drugs in combination with radiotherapy. Therefore, rather than discarding potential new drug combinations with radiotherapy, information regarding the possibility for unacceptable toxicities is needed and should be widely accessible to the cancer community prior to the initiation of clinical trials. One key issue is not only to find drugs that potentiate radiation response in tumour cells but also drugs that act selectively with a differential effect between normal tissue and tumour. For instance, gemcitabine‘s dramatic Toxicity when combined with radiation in early trials would have been detected by appropriate preclinical experiments and a classical dose escalation phase I methodology (Scalliet et al, 1998). In a similar manner, bevacizumab transfer into the clinic in combination with radiotherapy was done after two well-performed phase I trials (Willett et al, 2005; Crane et al, 2006) but no preclinical research was performed to define normal tissue toxicities or the optimal window of treatment when combined with radiation. At the moment where academic radiotherapy centres are competing to select the most promising agents to be combined to radiotherapy, the selection of valid preclinical criteria must be emphasised to minimise exposure of patients to potentially harmful toxicities. Toxicities assessment represents a major preclinical challenge to anticipate side effects during clinical trials where the definitive results will impact the outcome of combinations (Deutsch et al, 2005). The aim of the present study was therefore to evaluate normal tissue damage combining bevacizumab with radiation. We used well-characterised, easy-to-handle and reproducible models of radiation-induced Toxicity induced by single fraction irradiation in the gut (Withers and Elkind, 1970) (Acute Toxicity), Oral mucosa (Parkins et al, 1983) (subAcute Toxicity) and lung (Haston and Travis, 1997; Monceau et al, 2010) (late Toxicity), and we evaluated effect of a murin anti-VEGF antibody combined with radiotherapy with a robust preclinical study involving a large number of animals.
Thais Vital De Freitas – One of the best experts on this subject based on the ideXlab platform.
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Evaluation of the Acute Toxicity Oral of carnauba powder (PCO-C) in mice C57BL/6
Diabetology & Metabolic Syndrome, 2015Co-Authors: Paula Alves Salmito Rodrigues, José Ytalo Gomes Da Silva, Marcelo Oliveira Holanda, Carla Laíne Silva Lima, Raquel Teixeira Terceiro Paim, Sandra Machado Lira, Natalia Do Vale Canabrava, Mariana De Freitas Moreira, Juliana Barbosa Dantas, Thais Vital De FreitasAbstract:Evaluation of the Acute Toxicity Oral of carnauba powder (PCO-C) in mice C57BL/6 Paula Alves Salmito Rodrigues, Jose Ytalo Gomes da Silva, Marcelo Oliveira Holanda, Carla Laine Silva Lima, Raquel Teixeira Terceiro Paim, Sandra Machado Lira, Natalia do Vale Canabrava, Mariana de Freitas Moreira, Juliana Barbosa Dantas, Thais Vital de Freitas, Julianne do Nascimento Sales, Bruno Bezerra da Silva, Erlândia Alves Magalhaes Queiroz, Chayane Gomes Marques, Lia Magalhaes de Almeida, Icaro Gusmao Pinto Vieira, Francisca Noelia Pereira Mendes, Rafaela Valesca Rocha Bezerra Sousa, Arnaldo Solheiro Bezerra, Maria Izabel Florindo Guedes
Monica Mangoni – One of the best experts on this subject based on the ideXlab platform.
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Normal tissues toxicities triggered by combined anti-angiogenic and radiation therapies: hurdles might be ahead
British journal of cancer, 2012Co-Authors: Monica Mangoni, Marie-catherine Vozenin, Giampaolo Biti, Eric DeutschAbstract:Drugs developed to inhibit angiogenesis have now entered routine clinical practice in anticancer therapies. However, in most cases no permanent tumour control can be achieved, therefore the combination of anti-angiogenic strategies with cytotoxic agents such as chemotherapy, ionising radiation, or both represents a promising approach to increase cure rate of solid tumours (Koukourakis, 2001; Jain, 2005). Unfortunately angiogenesis is not tumour restricted but is also found in many other physiological and pathological conditions, for example, normal growth, wound healing and inflammation (Carmeliet and Jain, 2000) hence, inhibition of angiogenesis combined with other treatment may increase normal tissue Toxicity. US Food and Drug Administration has published a warning regarding the use of the anti-angiogenic agent bevacizumab (Avastin) in combination with chest radiotherapy (http://www.fda.gov/medwaTCH/safety/2007/Avastin_DHCP_TEF_Final8April2007.pdf) and several publications now report serious adverse events especially after treatment of thorax, gastrointestinal tract, head and neck and brain malignancies combining bevacizumab and radiotherapy (Willett et al, 2005; Crane et al, 2006; Carden et al, 2008; Seiwert et al, 2008; Gutin et al, 2009; Spigel et al, 2010; Lai et al, 2011). Most of these studies aimed at evaluating the anti-tumour efficacy of combined bevacizumab concurrently with radiotherapy in poor outcome situations however the results obtained indicate the need for caution in the development of bevacizumab and related drugs in combination with radiotherapy. Therefore, rather than discarding potential new drug combinations with radiotherapy, information regarding the possibility for unacceptable toxicities is needed and should be widely accessible to the cancer community prior to the initiation of clinical trials. One key issue is not only to find drugs that potentiate radiation response in tumour cells but also drugs that act selectively with a differential effect between normal tissue and tumour. For instance, gemcitabine’s dramatic Toxicity when combined with radiation in early trials would have been detected by appropriate preclinical experiments and a classical dose escalation phase I methodology (Scalliet et al, 1998). In a similar manner, bevacizumab transfer into the clinic in combination with radiotherapy was done after two well-performed phase I trials (Willett et al, 2005; Crane et al, 2006) but no preclinical research was performed to define normal tissue toxicities or the optimal window of treatment when combined with radiation. At the moment where academic radiotherapy centres are competing to select the most promising agents to be combined to radiotherapy, the selection of valid preclinical criteria must be emphasised to minimise exposure of patients to potentially harmful toxicities. Toxicities assessment represents a major preclinical challenge to anticipate side effects during clinical trials where the definitive results will impact the outcome of combinations (Deutsch et al, 2005). The aim of the present study was therefore to evaluate normal tissue damage combining bevacizumab with radiation. We used well-characterised, easy-to-handle and reproducible models of radiation-induced Toxicity induced by single fraction irradiation in the gut (Withers and Elkind, 1970) (Acute Toxicity), Oral mucosa (Parkins et al, 1983) (subAcute Toxicity) and lung (Haston and Travis, 1997; Monceau et al, 2010) (late Toxicity), and we evaluated effect of a murin anti-VEGF antibody combined with radiotherapy with a robust preclinical study involving a large number of animals.
Paula Alves Salmito Rodrigues – One of the best experts on this subject based on the ideXlab platform.
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Evaluation of the Acute Toxicity Oral of carnauba powder (PCO-C) in mice C57BL/6
Diabetology & Metabolic Syndrome, 2015Co-Authors: Paula Alves Salmito Rodrigues, José Ytalo Gomes Da Silva, Marcelo Oliveira Holanda, Carla Laíne Silva Lima, Raquel Teixeira Terceiro Paim, Sandra Machado Lira, Natalia Do Vale Canabrava, Mariana De Freitas Moreira, Juliana Barbosa Dantas, Thais Vital De FreitasAbstract:Evaluation of the Acute Toxicity Oral of carnauba powder (PCO-C) in mice C57BL/6 Paula Alves Salmito Rodrigues, Jose Ytalo Gomes da Silva, Marcelo Oliveira Holanda, Carla Laine Silva Lima, Raquel Teixeira Terceiro Paim, Sandra Machado Lira, Natalia do Vale Canabrava, Mariana de Freitas Moreira, Juliana Barbosa Dantas, Thais Vital de Freitas, Julianne do Nascimento Sales, Bruno Bezerra da Silva, Erlândia Alves Magalhaes Queiroz, Chayane Gomes Marques, Lia Magalhaes de Almeida, Icaro Gusmao Pinto Vieira, Francisca Noelia Pereira Mendes, Rafaela Valesca Rocha Bezerra Sousa, Arnaldo Solheiro Bezerra, Maria Izabel Florindo Guedes
Lin Kong – One of the best experts on this subject based on the ideXlab platform.
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Intensity-Modulated Proton and Carbon-Ion Radiation Therapy in the Management of Head and Neck Sarcomas.
Cancer medicine, 2019Co-Authors: Jing Yang, Jing Gao, Xianxin Qiu, Chenping Zhang, Lin KongAbstract:PURPOSE We report our experience of intensity-modulated proton and carbon-ion radiotherapy (IMPT/IMCT) for head and neck sarcomas (HNS). METHODS AND MATERIALS An analysis of the ongoing prospective data registry from the Shanghai Proton and Heavy Ion Center (SPHIC) for patients with HNS was conducted. The 12- and 24-month rates of local recurrence-free, overall, distant metastasis-free, progression-free survival (LRFS, OS, DMFS, and PFS), and Acute/late toxicities were calculated. The prognostic factors for the effectiveness of the treatment were also analyzed. RESULTS Between 7/2014 and 5/2018, 51 consecutive patients with HNS received definitive doses of IMCT (41 cases), IMPT (two cases), or their combination (eight cases). One patient had R0 resection and another treated on the Chinese Food and Drug Administration registration trial received IMPT only. Twenty-seven patients were treated according to various dose escalation trials or institutional protocols using IMCT or IMPT + IMCT boost. Twenty-two patients with locoregional recurrence (10 and four patients failed surgery or surgery followed by radiotherapy, respectively) or radiation-induced second primary sarcomas (eight patients) received salvage particle radiotherapy. With a median follow-up time of 15.7 months, four patients with second primary sarcoma died. The 1- and 2-year OS, PFS, LRFS, and DMFS rates for the entire cohort were 92.9% vs 90%, 73.6% vs 57.4%, 88.4% vs 78.9%, and 84.6% vs 76.5%, respectively. Those rates for patients without prior radiotherapy were 100% vs 100%, 82.1% vs 65.8%, 93.6% vs 85.3%, and 88.4% vs 79.5%, respectively. Multivariate analyses revealed that re-irradiation was an independent prognostic factor for both LRFS and PFS (P = 0.015 and 0.037, respectively). In addition, gross tumotumor volume (GTV) was an independent prognostic factor for PFS (P = 0.048). One patient experienced Grade 3 Acute Toxicity (Oral mucositis); another experienced Grade 4 Acute event (hemorrhage) which required embolization. He lately died from hemorrhage (Grade 5) at 3.4 months after the completion of treatment. No patient experienced radiation-induced Acute/late Toxicity of ≥ Grade 2 otherwise. CONCLUSION With few observed Acute/late toxicities, IMPT/IMCT provided effective short-term tumor control in our patients with HNS. Further investigations, preferably in a prospective fashion, will be required to confirm the efficacy and toxicities of IMPT/IMCT in this group of patients.