Overall Survival and Risk of Second Malignancies with Cancer Chemotherapy and G-CSF Support

Abstract

Background

The use of supportive granulocyte colony-stimulating factor (G-CSF) to reduce the risk of neutropenic complications in high-risk cancer patients is consistently recommended by several clinical practice guidelines. However, in a previous meta-analysis, G-CSF prophylaxis was associated with an increased risk of secondary malignancies while reducing long-term mortality. We present here an updated systematic review and meta-analysis.

Materials and methods

A systematic literature search was performed to identify randomized controlled trials of cancer patients receiving conventional-dose chemotherapy, assigned to primary G-CSF support or a control group without initial G-CSF, with at least 2 years of follow-up. Studies were categorized into 1 of 4 groups, based on the chemotherapy regimen and study design. An updated meta-analysis was performed; relative risk (RR) and 95% confidence intervals (CI) for all-cause mortality and secondary malignancies were calculated.

Results

Of 2604 articles screened, 14 eligible studies were identified and combined with studies identified in the previous systematic literature searches. The updated meta-analysis included a total of 68 studies presenting 71 separate comparisons. Survival was significantly improved in patients receiving primary G-CSF support, compared with patients without primary G-CSF support (mortality RR = 0.92; 95% CI: 0.90–0.95; P <0.0001). The largest improvement in survival was observed with dose-dense chemotherapy regimens with G-CSF support, compared with controls receiving no G-CSF support (mortality RR = 0.86; 95% CI: 0.80–0.92; P <0.0001). Patients who received primary G-CSF support experienced a significantly higher risk of secondary malignancies, compared with controls (RR = 1.85; 95% CI: 1.19–2.88; P <0.01).

Conclusions

Our findings demonstrate that overall survival is improved in patients receiving intensified chemotherapy with primary G-CSF support, compared to those receiving standard chemotherapy. Primary G-CSF support was also associated with a higher risk of developing secondary malignancies, including secondary acute myeloid leukemia and myelodysplastic syndrome.