4.1 Interventions to raise haemoglobin levels in patients with malignancies

4.1.1 Tumour hypoxia: pathophysiology and effects

Heterogeneously distributed hypoxic areas (pO2 <2.5 mm Hg) are seen in up to 60% of locally advanced solid tumours, such as breast, uterine, cervix, head, neck and rectal cancers, soft tissue sarcomas and malignant melanomas.156 A high incidence of hypoxic areas has been correlated with aggressive tumour behaviour and a propensity for metastasis.

Hypoxia affects signalling pathways involved in angiogenesis, glucose transport, pH regulation and erythropoiesis.157 Hence, tumours become hypoxic because of the development of abnormal vasculature. The hypoxia-inducible factor (HIF) family of transcription factors is important in the cellular response to oxygen homeostasis; overexpression of HIF-1 in human cancers correlates with poor prognosis and increased tumour aggression.158 Sustained tumour hypoxia alters the response to radiation and to many chemotherapeutic agents in cell lines, but this effect also depends on microenvironmental pH and glucose depletion.

Anaemia is common in patients with solid tumours, and is related to the tumour’s malignancy and treatment. An association between low haemoglobin levels and poor outcome of both radiotherapy and chemotherapy has been observed in various solid tumours.159,160 Reduced blood oxygen carrying capacity in anaemia may be a major contributor to tissue hypoxia, because the abnormal tumour vasculature is less able to compensate for anaemia by increasing tissue perfusion.