Risk factors for severe neutropenia in pancreatic cancer patients treated with gemcitabine/nab-paclitaxel combination therapy

Abstract

Aim Combination therapy with gemcitabine and nanoparticle albumin-bound paclitaxel (nab-paclitaxel), known as GnP therapy, significantly prolongs the survival of pancreatic cancer patients compared with gemcitabine monotherapy. However, it may cause severe neutropenia, requiring discontinuation of treatment. This study aimed to clarify the risk factors for Grade 3/4 neutropenia during GnP therapy. Methods Clinical data of pancreatic cancer patients who underwent GnP therapy at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research from December 2014 to December 2016 were retrospectively collected. The relationship of Grade 3/4 neutropenia onset to laboratory values and patient background factors was investigated by multivariate logistic regression analysis. Results Clinical data of 222 patients were analyzed. Grade 3/4 neutropenia occurred in 118 patients (53.2%) in the first cycle of GnP therapy. Multivariate analysis identified low absolute neutrophil count (ANC), high total bilirubin (T-Bil), and low C-reactive protein (CRP) as risk factors for Grade 3/4 neutropenia. Age was not a risk factor. The incidence of neutropenia was 85.7% in patients with all three risk factors, but only 27.7% in patients with none of them. Conclusion Low ANC, high T-Bil, and low CRP may be risk factors for Grade 3/4 neutropenia in patients receiving GnP therapy, even if these laboratory values are within normal reference ranges. Patients with these risk factors should be carefully monitored for adverse events.

Nomogram for predicting neutropenia in patients with esophageal, gastric, or colorectal cancer treated by chemotherapy in the first cycle

“…28 Decreased ANC has also been reported as an informative risk predictive factor in a variety of chemotherapy regimens. 29 Although some studies have shown that BMI could be used as a predictive factor, 30,31 it was not included in the final model in our study. One possible reason may be that the dose received by patients was calculated based on BMI.…”

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

“…The incidence rate of EOSN increased as the number of risk factors increased. Risk factors for severe neutropenia have been investigated in several malignancies, including gastrointestinal cancer, the identified factors partly depend on the cancer types and regimens (14)(15)(16)(17)(18)(19).…”

“…Second, it was unclear whether all risk factors were extracted. This study did not include hemoglobin, total bilirubin, or creatinine clearance, which were reported as risk factors in other studies ( 15 - 17 , 19 ). Further studies with larger sample sizes are required.…”

“…S e v e r a l s t u d i e s o n t h e r i s k f a c t o r s f o r s e v e r e chemotherapy-induced neutropenia have been reported in patients with solid tumors or hematologic malignancies (10)(11)(12)(13)(14)(15). The risk factors for neutropenia, regardless of the time of onset, were age over 65 years, low hemoglobin, high LDH, high creatinine, high bilirubin, and so on.…”

The double life of a chemotherapy drug: Immunomodulatory functions of gemcitabine in cancer

“…In cancer, the pro‐tumor and antitumor effects of neutrophils remain inconclusive 72 . Gemcitabine monotherapy, as well as its combination with other chemotherapies, may induce levels of neutropenia (and thrombocytopenia) that can be of clinical concern 73–75 . Surprisingly, incidence of chemotherapy‐induced neutropenia (CIN) has been correlated with improved survival in cancer patients, 76 and for gemcitabine‐treated pancreatic cancer patients, early‐onset CIN was identified as a predictor of more favorable prognosis 77 …”