Prediction of the responsiveness to treatment with erythropoiesis-stimulating factors: a prospective clinical study in patients with solid tumors.
OBJECTIVE
Treatment with erythropoiesis-stimulating factors (ESFs) can ameliorate anemia associated with cancer and chemotherapy. However, half of anemic cancer patients do not respond even to high doses. To determine factors that are predictive of a treatment response, a multicenter, prospective study was performed.


METHODS
Investigated factors were baseline erythropoietin, reticulocytes and soluble transferrin receptor (sTfR) after 2 weeks, and reticulocytes and hemoglobin after 4 weeks. Anemic patients with solid tumors received 150 microg/week of darbepoetin concomitantly with chemotherapy. The dose was doubled if hemoglobin did not increase by >1 g/dl after 4 weeks. Patients were considered responders if hemoglobin increased by >or=2 g/dl or reached a level >or=12 g/dl within 8-12 weeks.


RESULTS
In total, 196 patients were enrolled; 61% of the intention-to-treat (ITT) and 68% of the per-protocol population were responders. In the ITT population, the hemoglobin increase after 4 weeks indicated an 11-fold higher chance of response (odds ratio, 11.0; 95% confidence interval [CI], 5.1-23.6; sensitivity, 88%; specificity, 60%). In a multiple logistic regression model including all factors, the area under the receiver operating characteristic curve was 0.78 (95% CI, 0.71-0.84). The combination of sTfR after 2 weeks and hemoglobin after 4 weeks was as predictive as the combination of all five tested factors.


CONCLUSIONS
So far, an early hemoglobin increase remains the single most predictive factor for response to ESF treatment. In contrast to anemic patients with lymphoproliferative malignancies, serum erythropoietin had little predictive value in patients with solid tumors.
Steinmetz
Tilman
T
Oncologic Outpatient Clinics in Cologne, University of Cologne, Germany. steinmetz@oncokoeln.de
Hellmich
Martin
M
Neise
Michael
M
Aldaud
Ali
A
Lerchenmüller
Christian
C
Tsamaloukas
Antonis
A
Fandel
Francoise
F
Weiligmann
Christoph
C
Totzke
Uwe
U
Schmitz
Stephan
S
D000368:Aged; D000740:Anemia / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D004921:Erythropoietin / Q000097:blood / Q000627:therapeutic use*; D005260:Female; D006397:Hematinics; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications*; D011379:Prognosis; D011446:Prospective Studies; D012372:ROC Curve; D011994:Recombinant Proteins; D016896:Treatment Outcome
D006397:Hematinics; D006454:Hemoglobins; D011994:Recombinant Proteins; D004921:Erythropoietin