Randomized Double-Blind Trial of Combined Modality Treatment With or Without Amifostine in Unresectable Stage III Non–Small-Cell Lung Cancer

Abstract

Pretreatment with amifostine showed a trend toward reducing the severity of esophagitis associated with concurrent chemoradiotherapy, but it did not reach statistical significance. There was no significant protective effect on hematologic or neurologic toxicities induced by paclitaxel and carboplatin.

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

“…[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.…”

“…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.…”

“…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.…”

A pilot clinical trial assessing the efficacy and safety of supplementation with a B complex vitamin to reduce the incidence of chemotherapy induced peripheral neuropathy in patients diagnosed with a malignancy

“…Amifostine is a pharmaceutical agent that has had numerous studies conducted on it for the prevention of CIPN [6,7,[203][204][205][206][207][208][209][210][211][212][213][214][215]. The results are contentious with two studies cancelled due to harmful side effects, for example.…”

“…Fifteen trials have currently been conducted on Amifostine and CIPN [6,7,[203][204][205][206][207][208][209][210][211][212][213][214][215] with mixed results. Of the trials conducted there was one pilot trial [206], three non-randomised clinical trials [209,210,212], six randomised controlled trials [7, 203-205, 211, 215], one phase II open label trial 2-90 [214], three phase II double-blind placebo-controlled clinical trials [6,208,213] and one multi-centre phase III trial [207].…”