P-058 - Moderate neutropenia is a predictor of better prognosis in metastatic gastric cancer patients treated with the combination regimen of epirubicin, ox...

Date 04 July 2015
Event WorldGI 2015
Session Posters
Topics Cytotoxic agents
Complications/Toxicities of treatment
Gastric Cancer
Biological therapy
Presenter R. Liu
Citation Annals of Oncology (2015) 26 (suppl_4): 1-100. 10.1093/annonc/mdv233
Authors R. Liu, X. Zhu
  • Fudan University Shanghai Cancer Center, Shanghai/CN



EOF5 regimen, epirubicin combined with oxaliplatin and 5-day continuous infusion of 5-fluorouracil, is an effective regimen with acceptable safety profile in the treatment of metastatic gastric cancer (MGC). Neutropenia during chemotherapy has been reported to be a predictor of better prognosis in patients with several types of cancers. We aimed to assess whether chemotherapy-induced neutropenia could be associated with better overall survival (OS) and progression-free survival (PFS) in MGC patients who received EOF5 regimen.


We retrospectively analyzed 150 evaluable MGC patients enrolled in a previous phase II study, and each patient received EOF5 regimen as first line treatment. Neutropenia after each cycle and the most severe grade of neutropenia during total period of EOF5 treatment were recorded. Patients were classified into different groups according to the most severe grade of neutropenia during the treatment. Survival rate differences between groups were analyzed using log-rank tests. Multivariate analysis was performed using stepwise Cox proportional hazards regression modeling. To avoid a false-positive result due to a higher incidence of neutropenia with increasing chemotherapy cycles as a result of better survival, a landmark analysis is employed, limiting to 122 patients who received at least four cycles of chemotherapy and were alive 90 days after enrollment. As neutropenia varied over time, we regarded neutropenia as a time-varying covariate (TVC) in both the total group and landmark group.


Patients who developed moderate neutropenia (grade 1-3) had longer overall survival than those who without neutropenia (HR 0.48; p = 0.004). However, differ from previous similar studies, those experiencing severe neutropenia (grade 4) showed no significant difference (HR 0.88; p = 0.746). Therefore, we categorized all the patients into two groups: moderate group (grade 1-3) and absent/severe group (group 0, 4). According to a multivariate Cox model regarding neutropenia as a TVC, only 3 variables remained significant, the hazard ratio of OS for moderate neutropenia was 0.41 (p < 0.001) compared with absent/severe neutropenia. In landmark analysis, moderate neutropenia remained significant favorable prognostic factor for OS (HR 0.53; p = 0.018). For the association between moderate neutropenia and PFS, the hazard ratio for moderate neutropenia compared with absent/severe neutropenia was 0.37 (p < 0.001) and 0.49 (p = 0.010) respectively in the total group and landmark group. Among 49 patients who did not experience neutropenia during the first two cycles of treatment, 30 patients (61.2%) did not developed neutropenia during the following cycles of treatment, and only 6 patients (12.2%) developed grade 3 neutropenia (no grade 4 neutropenia).


Our results indicated that moderate neutropenia during chemotherapy could be a predictor for better OS and PFS in MGC patients received EOF5 regimen treatment. Prospective trials were required to identify whether an early dose escalation could be taken into consideration for patients without neutropenia in the first and second cycle.

Figure: P-058 (1) Kaplan–Meier survival curves according to the worst grade of EOF chemotherapy–induced neutropenia. Median overall survivals of grade 0 group, grade 1–3 group and grade 4 group were 6.83 months, 15.90 months and 8.93 months, respectively (p = 0.007). (2) Kaplan–Meier survival curves according to the worst grade of EOF chemotherapy–induced neutropenia. Median overall survivals of non-moderate group (grade 0,4) and moderate group (grade 1–3) were 7.27 months and 15.90 months, respectively (p = 0.002).