Combined Active Bone Marrow-Sparing Radiotherapy and Prophylactic PEG-rhG-CSF to Reduce Severe Neutropenia During Platinum-Doublet Concurrent Chemoradiotherapy for Locally Advanced Cervical Cancer: A Phase II Trial.

backgroundPlatinum-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%.

methodsPatients 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.

resultsFifty-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.

conclusionsThe 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 registrationChinese Clinical Trial Registry, ChiCTR2100046911. Registered May 30, 2021.