Risk factors and efficacy outcomes of early-onset severe neutropenia due to paclitaxel or nanoparticle albumin-bound paclitaxel combined with ramucirumab in advanced gastric cancer: a multicenter retrospective cohort study

Abstract

Background: Paclitaxel or nanoparticle albumin-bound paclitaxel combined with ramucirumab (PTX/ nab-PTX + RAM) is widely used as second-line chemotherapy for advanced gastric cancer (AGC), but severe neutropenia often develops with this regimen. Although previous studies have reported that severe neutropenia is a favorable prognostic factor in cancer chemotherapy, it is unclear in AGC patients receiving PTX/nab-PTX + RAM. In addition, the risk factors for early-onset of severe neutropenia (EOSN) still remain unknown.Methods: Among patients with AGC treated with PTX/nab-PTX (on day 1, 8, and 15) + RAM (on day 1 and 15) every 4 weeks as second-line therapy from January 2017 to June 2020, those with grade 0 or 1 neutropenia before the treatment were retrospectively studied. Blood tests were performed on the day of treatment each time, and disease progression was primarily determined by computed tomography every 8±2 weeks. EOSN was defined as grade 4 neutropenia that occurred during the first 28 days. The risk factors for EOSN were investigated using multivariate logistic regression analysis. Progression-free survival (PFS) and overall survival (OS) in patients with and without EOSN were investigated using multivariate analysis with a Cox proportional hazards model. Results:The clinical data of 244 patients were analyzed. EOSN was observed in 51 (20.9%) patients. Multivariate analysis identified the following five risk factors for EOSN: age >65 years [odds ratio (OR), 2.75],presence of primary tumor (OR, 2.82), presence of peritoneal metastasis (OR, 2.52), grade 1 neutropenia (OR, 3.32), and high serum level of alkaline phosphatase (OR, 2.34). The PFS was significantly longer in patients with EOSN than in those without EOSN [adjusted hazard ratio (HR), 0.61; 95% CI, 0.41-0.92] and the OS tended to be longer in patients with EOSN than in those without EOSN (adjusted HR, 0.73; 95% CI, 0.47-1.12). HR was adjusted with patient background factors and blood test data considered important as predictive or prognostic factors.Conclusions: EOSN may be associated with favorable outcomes in patients with AGC treated with PTX/ nab-PTX + RAM. We should carefully try to treat them keeping the risk factors in mind.

Inflammation Control and Tumor Growth Inhibition of Ovarian Cancer by Targeting Adhesion Molecules of E-Selectin

“…As mentioned in the result, the BSANPs-PTX- and PTX-treated groups had lower neutrophil counts than healthy mice, while the platelet level for the BSANPs-PTX group was higher than in healthy mice and that of the PTX group was lower than the healthy group. Studies showed the neutrophils and platelet levels can be related to outcome and recovery following chemotherapy [ 52 , 54 ], and thus, it can be predicted that ESBP-BSANPs-PTX treatment may lead to better hematological recovery and outcome than BSANPs-PTX and PTX treatments. This prediction is supported by the prolonged survival time of the ESBP-BSANPs-PTX-treated mice.…”