G-CSF safe during chemoradiotherapy for SCLC
The use of granulocyte colony stimulating-factor (G-CSF) is safe in patients with limited-stage small-cell lung cancer (SCLC) treated with chemoradiotherapy, according to a post hoc analysis of the phase III CONVERT trial presented at the European Lung Cancer Conference (ELCC) 2017.
The results showed a significantly increased incidence of grade 3/4 thrombocytopenia (29.4 vs 13 percent; p<0.001) and grade 3/4 anaemia (20.9 vs 8.3 percent; p=0.004) in patients who received G-CSF vs those who did not. [ELCC 2017, abstract LBA2_PR]
“However, these rates were lower than previously reported,” said lead author Dr Fabio Gomes of the Christie NHS Foundation Trust, Manchester, UK. “The use of G-CSF did not increase the risk of severe acute oesophagitis or pneumonitis. Overall survival [OS] and progression-free survival [PFS] were similar between patients who used G-CSF and those who did not.”
The CONVERT trial included 547 patients with limited-stage SCLC who were randomized to receive concurrent chemoradiotherapy with once-daily (66 Gy 33 fractions) or twice-daily (45 Gy 30 fractions) radiotherapy. [ASCO 2016, abstract 8504] The trial protocol allowed the use of G-CSF, which is controversial as the American Society of Clinical Oncology (ASCO) recommends against its routine use during concurrent chemoradiotherapy in SCLC. [J Clin Oncol 2015;33:3199-3212]
“This recommendation was based on a randomized trial conducted between 1989 and 1991, which showed a significant increase in severe thrombocytopenia, severe anaemia, pulmonary complications and toxic deaths when granulocyte-macrophage CSFs [GM-CSFs] were used during concurrent chemoradiotherapy,” explained Gomes. [J Clin Oncol 1995;13:1632-1641]
“However, GM-CSFs act on more than one blood cell lineage and are not commonly used nowadays. In contrast, G-CSFs are more specific as they aim for the neutrophil lineage only,” he noted. “Furthermore, radiotherapy techniques have become more precise today, which reduces the risk of toxicity.”
“We can conclude from this analysis that the use of G-CSF during thoracic radiotherapy is safe and should support patients to receive the full planned course of concurrent chemoradiotherapy,” he suggested. “Our findings give clinicians confidence to use G-CSF when needed in this context.”
In the trial, 33 percent of patients received at least one cycle of prophylactic G-CSF, while 41 percent received prophylactic and/or therapeutic G-CSF. The use of G-CSF increased from 11 percent in cycle 1 to 27 percent in cycle 4.
Antibiotic use was also allowed in the trial. Forty-eight percent of patients received prophylactic antibiotics, but its used decreased from 41 percent in cycle 1 to 20 percent in cycle 3. Prophylactic use of antibiotics was associated with significantly worse OS (p=0.016) and PFS (p=0.03).
“Although the use of G-CSF did not increase the risk of pneumonitis in this analysis, the incidence of severe thrombocytopenia is a concern. Based on these results, we can conclude that primary or secondary prophylaxis of febrile neutropenia with G-CSF is justified, but patients at higher risk of thrombocytopenia should be treated with caution,” commented Dr Stefan Zimmermann of the HFR – Hôpital Cantonal, Fribourg, Switzerland.