Use of G-CSF and prophylactic antibiotics with concurrent chemo-radiotherapy in limited-stage small cell lung cancer: Results from the Phase III CONVERT trial

Abstract

Background: Concurrent chemo‐radiotherapy (CTRT) is the optimal treatment for limited‐stage small cell lung cancer. The use of granulocyte colony stimulating‐factor (G‐CSF) in this context is controversial and its routine use is not recommended after a report of higher toxicity but the safety data is scarce. The use of prophylactic antibiotics is also not standardised. Methods: In a phase 3 trial, 547 patients (pts) were randomised between oncedaily RT (66Gy 33 fractions) or twice‐daily (45Gy 30 fractions) with chemotherapy (cisplatin/etoposide). The use of prophylactic G‐CSF and antibiotics was permitted. Results: 33%of pts received at least 1 cycle of prophylactic G‐CSF and 41%received prophylactic and/or therapeutic G‐CSF. Its use increased from 11% at cycle 1 to 27% at cycle 4. Prophylactic antibiotics were used in 48% of pts but its use decreased from 41%to 20%. The use of antibiotics and/or G‐CSF was similar in both arms. The incidence of grade 3/4 thrombocytopenia was higher in pts with G‐CSF (29.4%vs. 13%; p<0.001) with similar results in both arms. The incidence of grade 3/4 anaemia in pts with G‐CSF was only significantly increased in the twice‐daily arm(20.9%vs. 8.3%; p=0.004). 11 pts had acute pneumonitis grade 3/4 and 96 had acute esophagitis grade 3/4. There was no significant association with the use of G‐CSF. The overall survival (OS) and progression free survival (PFS) were similar independently of G‐CSF use in either arm. Pts with prophylactic antibiotics were associated with worse OS (p=0.016) and PFS (p=0.03). Conclusions: The use of G‐CSF with modern radiotherapy techniques during CTRT does not result in an increased risk of severe acute esophagitis or pneumonitis. Despite an increased incidence of severe thrombocytopenia and anaemia, the use of G‐CSF was not detrimental in PFS or OS.