Abstract / Summary
Background: Platinum-doublet concurrent chemoradiotherapy (CCRT) for locally advanced cervical cancer (LACC) is frequently complicated by severe neutropenia. This Phase II trial investigated whether combining active bone marrow-sparing (ABMS) radiotherapy with prophylactic pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) could reduce the incidence of grade ≥ 3 neutropenia below a prespecified historical benchmark of 30%.
Methods: Patients with FIGO 2018 stage IIA2-IVA LACC received SPECT-guided ABMS radiotherapy (45 Gy external beam plus 30 Gy brachytherapy) concurrent with paclitaxel/carboplatin every 21 days for 4 cycles followed by prophylactic PEG-rhG-CSF. Using Simon's two-stage design (α = 0.05, β = 0.20), we tested whether grade ≥ 3 neutropenia could be reduced from a historical benchmark of 30% to ≤ 15%. The primary endpoint was grade ≥ 3 neutropenia incidence; secondary endpoints included other cytopenias, treatment completion, and survival outcomes.
Results: Fifty-four patients were enrolled. Grade ≥ 3 neutropenia occurred in 13.0% (7/54; 95% CI: 5.4%-24.9%), meeting the prespecified success criterion (one-sided exact binomial test, p = 0.003 versus the 30% benchmark). Other grade ≥ 3 toxicities included leukopenia (18.5%), anemia (3.7%), thrombocytopenia (5.6%), and febrile neutropenia (1.9%). Overall, 85.2% of patients completed all 4 planned chemotherapy cycles, and all completed radiotherapy within 8 weeks (median overall treatment time: 50 days). At a median follow-up of 40 months, the 3-year progression-free survival (PFS) and overall survival (OS) rates were 88.8% and 88.9%, respectively (6 events each); the study was not powered for survival efficacy.
Conclusions: The combination of ABMS radiotherapy and prophylactic PEG-rhG-CSF was associated with a grade ≥ 3 neutropenia rate of 13.0% and a chemotherapy completion rate of 85.2% during platinum-doublet CCRT for LACC. Because the single-arm design and reliance on historical controls preclude causal inference, these findings are hypothesis-generating and primarily establish the operational feasibility of this dual hematoprotection approach. Formal evaluation of safety and efficacy requires the ongoing randomized trial (ChiCTR2400087321).
Trial registration: Chinese Clinical Trial Registry, ChiCTR2100046911. Registered May 30, 2021.