High serum levels of TNF-α and IL-6 predict the clinical outcome of treatment with human recombinant erythropoietin in anaemic cancer patients.
BACKGROUND
A number of anaemic cancer patients are not responsive to treatment with recombinant human erythropoietin (rHuEPO). The aim of the present study is to investigate whether serum levels of tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6 and additional laboratory parameters, together with clinical variables, can predict the clinical outcome of treatment with rHuEPO in anaemic cancer patients.


METHODS
Thirty-five cancer patients and 25 healthy controls were enrolled in this study. Patients were treated with epoetin alfa at the dose of 150 IU/kg s.c. three times a week for 12 weeks. If the haemoglobin (Hb) level failed to improve at least 2 g/dl above baseline by week 6 of treatment, dose was increased to 300 IU/kg s.c. for the remainder of the treatment period. All patients filled out the Brief Fatigue Inventory (BFI), a questionnaire for the self-evaluation of cancer-related fatigue. Serum samples from patients and control groups were frozen at -80 degrees C and TNF-alpha, IL-1beta and IL-6 were later examined by enzyme-linked immunosorbent assay.


RESULTS
Fatigued cancer patients had significant higher levels of circulating TNF-alpha, IL-1beta and IL-6 than healthy controls. Responders (Rs) to erythropoietin had significant lower medium levels of TNF-alpha and IL-6 than nonresponders (NRs). Fatigued patients with a general BFI score > or =6 presented higher medium level of cytokines than nonfatigued patients (general BFI score <6), but each group responded similarly to treatment with rHuEPO.


CONCLUSIONS
High serum levels of TNF-alpha and IL-6 at the baseline are significantly correlated with a negative response to administration with rHuEPO. Thus, pretreatment evaluation of TNF-alpha and IL-6 serum levels can help to select those patients who are most likely to benefit from treatment with rHuEPO. On the contrary, Hb level, red blood cell count, lactate dehydrogenase and BFI score do not predict the outcome of treatment with rHuEPO.
Pavese
I
I
Departments of Oncology.
Satta
F
F
Departments of Oncology.
Todi
F
F
Departments of Oncology.
Di Palma
M
M
Departments of Oncology.
Piergrossi
P
P
Clinical Pathology.
Migliore
A
A
Medicine, San Pietro Fatebenefratelli Hospital.
Piselli
P
P
Department of Statistics, National Institute 'L. Spallanzani' Istituto di Ricerca e Cura a Carattere Scentifico.
Borghesi
R
R
San Pietro FBF Research Center, San Pietro FBF Hospital, Rome, Italy.
Mancino
G
G
San Pietro FBF Research Center, San Pietro FBF Hospital, Rome, Italy.
Brunetti
E
E
San Pietro FBF Research Center, San Pietro FBF Hospital, Rome, Italy.
Alimonti
A
A
Departments of Oncology; San Pietro FBF Research Center, San Pietro FBF Hospital, Rome, Italy. Electronic address: alimonti.andrea@fbfrm.it.
D000368:Aged; D000740:Anemia / Q000139:chemically induced / Q000175:diagnosis / Q000188:drug therapy*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000627:therapeutic use*; D005260:Female; D006397:Hematinics / Q000627:therapeutic use; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology; D011994:Recombinant Proteins; D015996:Survival Rate; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
D006397:Hematinics; D006454:Hemoglobins; D015850:Interleukin-6; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D004921:Erythropoietin; D000068817:Epoetin Alfa