Effect of amifostine on toxicities associated with radiochemotherapy in patients with locally advanced non–small-cell lung cancer

Antonadou, D.; Throuvalas, Nikolas; Petridis, A.; Bolanos, N.; Sagriotis, A.; Synodinou, M.

doi:10.1016/s0360-3016(03)00590-x

Cited by 86 publications

(39 citation statements)

References 29 publications

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“…[9][10][11][12][25][26][27][28][29][30][31] With the availability of sophisticated computer-controlled modification systems for clinical radiotherapy dose distribution by modern linear accelerators including intensity-modulated radiation therapy, 1,2,7 many physical barriers to dose optimization in complex tumor volumes have been overcome. Unfortunately, effective high dose delivery to complex tumor volumes in the thoracic cavity, which has been developed for patients with lung cancer, esophagus cancer, and other thoracic malignancies, has necessitated often large lung transit volumes and associated toxicity.…”

Section: Discussionmentioning

confidence: 99%

“…Pharmacologic interventions and biologic response modifiers have recently been focused on pulmonary radiation protection. Intravenous or systemic delivery of compounds such as WR2721 (Amifostine), [9][10][11][26][27][28][29]32 colony stimulating factors, 31 or other antioxidant molecules 30,33,34 has the potential problem of distribution to tumor vasculature within the target volume. 27,29 Simultaneous tumor and normal tissue radiation protection would not alter the therapeutic ratio or shift to a desirable effect of normal tissue radiation protection.…”

Section: Discussionmentioning

confidence: 99%

“…2,8 Since most lung and all esophageal cancers are central mediastinal in anatomic location, transit volumes involving both lungs are common in radiotherapy treatment plans. [1][2][3][9][10][11] Dose escalation protocols to attempt to derive local control in over 30% of patients with gross tumor are rarely possible due to lung toxicity. 2,3,5,6 A biological response modifier approach toward decreasing pulmonary toxicity would be valuable to facilitate new improvements in radiation treatment.…”

Section: Introductionmentioning

confidence: 99%

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Inhalation delivery of manganese superoxide dismutase-plasmid/liposomes protects the murine lung from irradiation damage

et al. 2005

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Intratracheal injection of manganese superoxide dismutaseplasmid/liposome (MnSOD-PL) complexes has been demonstrated to delay the onset and reduce the extent of ionizing irradiation-induced murine pulmonary organizing alveolitis/ fibrosis. To facilitate translation of this modality to clinical fractionated radiotherapy, inhalation delivery of MnSOD-PL was developed using an ultrasonic nebulizer. Transgene product was quantitated by immunohistochemical quantitation and pulmonary tissue levels of MnSOD biochemical activity. C57BL/6NHsd female mice demonstrated a plasmid dose-dependent increased expression of MnSOD transgene product over the range of 250 mg-2.5 mg of MnSOD-PL administered over a constant 5 min interval. Delivery of a constant concentration of 500 mg of MnSOD-PL with varying times of administration ranging from 0.5 to 10 min demonstrated optimal MnSOD expression at 5 min. Mice pretreated by inhalation delivery of MnSOD-PL demonstrated significantly improved survival after 20 Gy single fraction irradiation to both lungs compared to LacZ-PL inhalation-treated or irradiated control mice. Mice receiving 10 fractions of 3.5 cGy demonstrated increased pulmonary MnSOD transgene product activity by a protocol of every Monday-Wednesday or daily inhalation of MnSOD-PL. Thus, inhalation radioprotective gene therapy using MnSOD-PL provides a practical and effective method for delivery of lung-specific radioprotection during fractionated radiotherapy protocols in a mouse model. Gene Therapy (2005) 12, 685-693.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Inhalation delivery of manganese superoxide dismutase-plasmid/liposomes protects the murine lung from irradiation damage

et al. 2005

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“…In addition to its high efficacy in ameliorating xerostomia resulting from irradiation (4,5), high frequencies of deleterious side effects (nausea, cutaneous reactions, hypotension, etc.) and even tumor radioprotection have been reported, which limit its use (6)(7)(8)(9). Therefore, the search for other radioprotectors with high potency and low toxicity should be the primary subject of further research.…”

Section: Introductionmentioning

confidence: 99%

Research progress in the radioprotective effect of superoxide dismutase

et al. 2012

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Irradiation from diverse sources is ubiquitous and closely associated with human activity. Radiation therapy (RT), an important component of the multiple radiation origins, contributes significantly to oncotherapy by killing tumor cells. On the other hand, RT can also cause some undesired normal tissue injuries that afflict numerous cancer patients. Although many promising radioprotective agents are emerging, few of them have entered the market successfully due to various limitations. At present, the most accepted hypothesis for the radiation-caused injury involves reactive oxygen species (ROS) generation. Superoxide dismutase (SOD), the unique enzyme responsible for the dismutation of superoxide radicals, is expected to occupy an indispensable position in the treatment of ROS-mediated tissue injuries originating from exposure to radiation. This review focuses on the mechanism of radioprotection by SOD at the tissue or organ level, cellular level, and molecular level, respectively, in order to provide references for further investigation of radiation injury and development of new radioprotectors.

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“…In addition, increased retching from nausea and vomiting, a tirapazamine-related toxicity, may also contribute to symptomatic esophagitis. The addition of amiphostine, which has been shown to decrease esophagitis and pneumonitis in NSCLC patients treated with concurrent thoracic irradiation and chemotherapy (38), may help to ameliorate many of the side effects noted in this study.…”

Section: Discussionmentioning

confidence: 91%

Phase I Study of Tirapazamine Plus Cisplatin/Etoposide and Concurrent Thoracic Radiotherapy in Limited-Stage Small Cell Lung Cancer (S0004)

McCoy

Williamson

et al. 2004

Clinical Cancer Research

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Group study in LSCLC that used the same concurrent chemoradiotherapy without tirapazamine, the present trial showed a higher rate of grade 3-4 esophagitis (34% versus 22%), vomiting (34% versus 23%), and febrile neutropenia (7% versus 2%). The consolidation phase was relatively well tolerated, with grade 4 neutropenia in 44% and febrile neutropenia in 5% of patients. There were two treatmentrelated deaths: one from neutropenic fever and one from respiratory infection. The overall response rate was 80%, and the median survival was 22 months. Conclusions: Protocol-defined dose-limiting toxicity was observed at the initial tirapazamine dose, precluding dose escalation. Compared with S9713, the addition of tirapazamine increased the incidence of vomiting, neutropenia, and febrile neutropenia, although the overall toxicity profile remained acceptable. In view of the observed favorable survival, further study of tirapazamine in LSCLC is warranted.

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Effect of amifostine on toxicities associated with radiochemotherapy in patients with locally advanced non–small-cell lung cancer

Cited by 86 publications

References 29 publications

Inhalation delivery of manganese superoxide dismutase-plasmid/liposomes protects the murine lung from irradiation damage

Inhalation delivery of manganese superoxide dismutase-plasmid/liposomes protects the murine lung from irradiation damage

Research progress in the radioprotective effect of superoxide dismutase

Phase I Study of Tirapazamine Plus Cisplatin/Etoposide and Concurrent Thoracic Radiotherapy in Limited-Stage Small Cell Lung Cancer (S0004)

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