Hematopoietic Growth Factors Reduce Side Effects of Cancer Treatment: Results of Two Comprehensive Meta-Analyses.

Background: Hematopoietic growth factors such as G-CSF/GM-CSF and erythropoietin (EPO) are used in clinical practice to reduce side effects of cancer treatment but also to improve tumour response and overall survival. We conducted two meta-analyses on the effects of hematopoietic growth factors in the treatment of malignant diseases a) to determine the effectiveness of G-CSF and GM-CSF to i) prevent infection, ii) improve tumor response and overall survival in lymphoma patients undergoing standard chemotherapy and b) to assess the effectiveness of EPO to i) prevent anemia, ii) improve tumor response and overall survival in cancer patients.

Methods: The Cochrane Library, Medline, Embase and smaller databases were searched. Randomized controlled trials comparing G-CSF/GM-CSF or EPO versus placebo/no treatment were included in the reviews. Both study arms had to receive identical antineoplastic treatment and identical additional supportive care. We included full-text and abstract publications as well as unpublished data. Data were meta-analysed using fixed and random effects models.

Results: Twenty one trials with 2,794 adults were included in the EPO meta-analysis. Use of EPO significantly reduced the relative risk of red blood cell transfusions (RR 0.67; 95% CI 0.62 to 0.73). For participants with baseline hemoglobin below 10 g/dL hematological response was observed more often in participants receiving EPO (RR 3.60; 95% CI 3.07 to 4.23). There was inconclusive evidence whether EPO improves tumour response (random effects: RR 1.21; 95% CI 0.92–1.59) and overall survival (unadjusted data: HR 0.84; 95% CI 0.69 to 1.02). 12 trials with 1,823 randomized patients were included in the G-CSF/GM-CSF meta-analysis. Compared with no prophylaxis, G-CSF/GM-CSF significantly reduced the relative risk for infections (RR 0.74; 95% CI 0.64–0.85). There was no evidence for G-CSF/GM-CSF to decrease infection related mortality (RR 1.37; 95% CI 0.66–2.32), to improve complete response (RR 1.02; 95% CI 0.94–1.11) or overall survival (HR 1.00; 95% CI 0.86–1.16).

Conclusions: There is consistent evidence that the administration of EPO and G-CSF/GM-CSF reduces the side effects of antineoplastic therapy, such as risk for blood transfusions (EPO) and infections (G-CSF/GM-CSF). However, there is inconclusive evidence whether the administration of hematopoietic growth factors in these clinical settings also improve tumor response and overall survival.