Decrease of erythropoietin level by human recombinant tumour necrosis factor alpha (hrec TNFalpha) in patients with advanced cancer

Anaemia is a frequent complication of chronic inflammation, infectious diseases and cancer. Inappropriate erythropoietin production is regarded as one of the main causative factors responsible for the occurrence of anaemia. The pathogenesis of TNFalpha induced-anaemia has not been fully clarified yet and its influence on hematopoiesis has been suggested. We performed a clinical study to access the influence of hrec TNFalpha administration on plasma EPO concentration and the degree of anaemia in patients with advanced solid tumours for whom no other kind of therapy but palliative treatment was available. All these patients exposed mild anaemia (HT 36.1 +/- 1.0%). Plasma EPO was estimated at 8 a.m. before and after 5 days of TNFalpha therapy with a dose of 75 pg/day iv (cycle I). Two weeks later plasma EPO was estimated again before and after 5 days of TNFalpha administration of a double dose (150 microg/day) (cycle II). The control group comprised 8 non-cancer patients (5M/3F, age 48.5 +/- 6yr) with the same degree of anaemia (HT 36 +/- 1.1%) due to haemorrhage. In the control group the plasma EPO level was significantly higher (54.2 +/- 8 mU/ml) than in cancer patients before cycle I (17.1 +/- 2.5 mU/ml) and II (14.6 +/- 3.8 mU/ml) respectively.TNF administration was followed by a significant decline of plasma EPO both after the first (17.1 +/- 2.5 vs 9.0 +/- 1.5 mU/ml) and second cycle (14.6 +/- 3.8 vs 8.4 +/- 2.0 mU/ml) of TNF treatment.

Patients with solid cancer and mild anaemia are characterised by inappropriate low plasma EPO concentration. Therapy with TNFalpha exerts a suppressive effect on EPO secretion in these patients.