Anaemia is of prognostic significance in patients with oesophageal adenocarcinoma

Tanswell, I; Steed, Helen; Butterworth, Jeffrey; Townson, G

doi:10.4997/jrcpe.2011.304

Cited by 5 publications

(4 citation statements)

References 13 publications

(19 reference statements)

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“…This study provides a basis for assessing the utility of deferasirox in the treatment of patients with oesophageal cancer. It is of particular note that anaemia in GI cancers is common, with up to 45% of oesophageal cancer patients being anaemic (Tanswell et al ., ). The results from the current study suggest that administration of deferasirox at appropriate doses would have no effect on their systemic iron levels and thus would not compound the level of their anaemia.…”

Section: Discussionmentioning

confidence: 97%

Deferasirox (ICL670A) effectively inhibits oesophageal cancer growth in vitro and in vivo

Ford

Obeidy

Lovejoy

et al. 2013

British J Pharmacology

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BACKGROUND AND PURPOSEGrowing evidence implicates iron in the aetiology of gastrointestinal cancer. Furthermore, studies demonstrate that iron chelators possess potent anti-tumour activity, although whether iron chelators show activity against oesophageal cancer is not known. EXPERIMENTAL APPROACHThe effect of the iron chelators, deferoxamine (DFO) and deferasirox, on cellular iron metabolism, viability and proliferation was assessed in two oesophageal adenocarcinoma cell lines, OE33 and OE19, and the squamous oesophageal cell line, OE21. A murine xenograft model was employed to assess the effect of deferasirox on oesophageal tumour burden. The ability of chelators to overcome chemoresistance and to enhance the efficacy of standard chemotherapeutic agents (cisplatin, fluorouracil and epirubicin) was also assessed. KEY RESULTSDeferasirox and DFO effectively inhibited cellular iron acquisition and promoted intracellular iron mobilization. The resulting reduction in cellular iron levels was reflected by increased transferrin receptor 1 expression and reduced cellular viability and proliferation. Treating oesophageal tumour cell lines with an iron chelator in addition to a standard chemotherapeutic agent resulted in a reduction in cellular viability and proliferation compared with the chemotherapeutic agent alone. Both DFO and deferasirox were able to overcome cisplatin resistance. Furthermore, in human xenograft models, deferasirox was able to significantly suppress tumour growth, which was associated with decreased tumour iron levels. CONCLUSIONS AND IMPLICATIONSThe clinically established iron chelators, DFO and deferasirox, effectively deplete iron from oesophageal tumour cells, resulting in growth suppression. These data provide a platform for assessing the utility of these chelators in the treatment of oesophageal cancer patients.

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Section: Discussionmentioning

confidence: 97%

Deferasirox (ICL670A) effectively inhibits oesophageal cancer growth in vitro and in vivo

Ford

Obeidy

Lovejoy

et al. 2013

British J Pharmacology

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“…This limitation has been acknowledged in previous studies. 19 This, in turn, may have influenced the average blood parameter values for the overall OAC cohort. In vitro and in vivo evidence suggests iron chelation to be a promising and safe adjunct to oesophageal cancer treatment.…”

Section: Discussionmentioning

confidence: 99%

“…17 Previous studies in oesophageal cancer have estimated the incidence of anaemia on presentation to range from 20% to 45%. 18,19 Clearly, any benefit seen for patients treated with iron chelation therapy in terms of antineoplastic activity or chemosensitisation would be substantially negated by the development of iron deficiency and/or anaemia and its associated side effects.…”

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confidence: 99%

A comparative study of the iron status of patients with oesophageal adenocarcinoma to determine suitability for a clinical trial of iron chelation therapy

Ford

Bedford²,

Pang

et al. 2014

annals

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INTRODUCTIONThe incidence of oesophageal adenocarcinoma (OAC) is rising dramatically and overall survival remains extremely poor. Iron has been shown to potentiate tumourigenesis in OAC, and iron chelation therapy demonstrates promise in vivo as an adjunct to neoadjuvant and palliative chemotherapy. OAC, however, has traditionally been associated with iron deficiency anaemia. The aim of this study was therefore to formally quantify the iron status of OAC patients in order to guide the design of future clinical trials involving iron chelation therapy. METHODS Demographic and cancer specific data were collected prospectively from all patients presenting with OAC and gastric adenocarcinoma (GAC). Patients had haemoglobin, serum iron, serum ferritin and serum transferrin receptor (sTfR) levels measured to assess systemic iron status. In addition, the sTfR/log ferritin (sTfR-F) index was calculated. RESULTS Average haemoglobin, serum iron, serum ferritin, sTfR and sTfR-F index values for all patients presenting with OAC were within normal sex specific reference ranges. No statistical difference in iron status was observed between OAC patients presenting with resectable and advanced OAC. Patients with OAC are relatively iron replete compared with those presenting with GAC. Iron parameters were not significantly altered by standard neoadjuvant chemotherapy. CONCLUSIONS Patients presenting with resectable or advanced OAC could be considered as candidates for a clinical trial of iron chelation therapy as an addition to standard neoadjuvant or palliative treatments.

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“…In addition to this, the tolerability of standard chemotherapeutic regimes to patients in either the neo‐adjuvant or palliative setting is poor. It is also known that anaemia can complicate oesophageal cancer in up to 45% of cases (Melis et al ., ; Tanswell et al ., ), and the chemotherapeutic regimes used in cancer chemotherapy may exacerbate this anaemia. These factors combine to highlight why further advances in the management of oesophageal carcinoma are so desperately needed.…”

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confidence: 99%

Iron chelation: a potential therapeutic strategy in oesophageal cancer

Keeler

Brookes

2013

British J Pharmacology

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Raised intracellular iron has been identified as a potential aetiological factor in the development of several epithelial malignancies, including those of the gastrointestinal tract. The mechanism behind this increase is thought to include disorders of iron uptake and storage. Several iron chelators have been identified as potential anti-tumour agents, with much work undertaken to ascertain the exact mode of action. Despite this, there is little known about the role that these drugs play in the cellular iron metabolism of oesophageal cancer. Consequently, the present study looks to review the relationship of two clinically important iron-chelating agents, deferoxamine and deferasirox, on cellular iron uptake and storage in oesophageal squamous and adenocarcinoma. This provides important evidence for the debate about the role these agents have in the clinical management of such tumours.

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Anaemia is of prognostic significance in patients with oesophageal adenocarcinoma

Cited by 5 publications

References 13 publications

Deferasirox (ICL670A) effectively inhibits oesophageal cancer growth in vitro and in vivo

Deferasirox (ICL670A) effectively inhibits oesophageal cancer growth in vitro and in vivo

A comparative study of the iron status of patients with oesophageal adenocarcinoma to determine suitability for a clinical trial of iron chelation therapy

Iron chelation: a potential therapeutic strategy in oesophageal cancer

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