G H Lyman1, L Yau2, R Nakov2, A Krendyukov3. 1. Hutchinson Institute for Cancer Outcomes Research, Fred Hutchinson Cancer Research Center, Seattle; University of Washington School of Medicine, Seattle, USA. 2. Hexal AG, Holzkirchen, Germany. 3. Hexal AG, Holzkirchen, Germany. Electronic address: andriy.krendyukov@sandoz.com.
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 carried out 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 one of the four groups, based on the chemotherapy regimen and study design. An updated meta-analysis was carried out; relative risk (RR) and 95% confidence intervals (CIs) 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; ARD=-3.3%; 95% CI -4.2--2.4; 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; ARD=0.47; 95% CI 0.21-0.73; P < 0.01). Conclusions: Our findings demonstrate that overall survival is improved in patients receiving intensified chemotherapy with primary G-CSF support, compared with 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.
Background: The use of supportive granulocyte colony-stimulating factor (G-CSF) to reduce the risk of neutropenic complications in high-risk cancerpatients 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 carried out to identify randomized controlled trials of cancerpatients 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 one of the four groups, based on the chemotherapy regimen and study design. An updated meta-analysis was carried out; relative risk (RR) and 95% confidence intervals (CIs) 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; ARD=-3.3%; 95% CI -4.2--2.4; 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; ARD=0.47; 95% CI 0.21-0.73; P < 0.01). Conclusions: Our findings demonstrate that overall survival is improved in patients receiving intensified chemotherapy with primary G-CSF support, compared with 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.
Authors: Hafsa Munir; James O Jones; Tobias Janowitz; Markus Hoffmann; Maximilien Euler; Carla P Martins; Sarah J Welsh; Jacqueline D Shields Journal: Nat Commun Date: 2021-01-29 Impact factor: 14.919
Authors: Pablo Sala Elarre; Esther Oyaga-Iriarte; Kenneth H Yu; Vicky Baudin; Leire Arbea Moreno; Omar Carranza; Ana Chopitea Ortega; Mariano Ponz-Sarvise; Luis D Mejías Sosa; Fernando Rotellar Sastre; Blanca Larrea Leoz; Yohana Iragorri Barberena; Jose C Subtil Iñigo; Alberto Benito Boíllos; Fernando Pardo; Javier Rodríguez Rodríguez Journal: Cancers (Basel) Date: 2019-04-30 Impact factor: 6.639