Chemotherapy-induced neutropenia as a prognostic factor in patients with pancreatic cancer treated with gemcitabine plus nab-paclitaxel: a retrospective cohort study

Kan, Motoyasu; Imaoka, Hiroshi; Watanabe, Kazuo; Sasaki, Mitsuhito; Takahashi, Hideaki; Hashimoto, Yusuke; Ohno, Izumi; Mitsunaga, Shuichi; Umemoto, Kumiko; Kimura, Gen; Eguchi, Hiroki; Otsuru, Toru; Goda, Kyosuke; Ikeda, Masafumi

doi:10.1007/s00280-020-04110-3

Cited by 8 publications

(6 citation statements)

References 27 publications

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“…In a large pooled analysis of 1529 patients with NSCLC treated with chemotherapy in 6 randomized studies, chemotherapy-induced neutropenia was significantly associated with a longer overall survival, especially in patients who developed severe neutropenia [ 30 ]. Similar findings were reported in pancreatic cancer [ 31 ], gastric cancer [ 32 ], and metastatic castration-resistant prostate cancer [ 33 ]. There is increasing evidence that tumor-associated myeloid cells play a crucial role in tumor development, metastatic progression, and the immunosuppressive microenvironment of many cancers [ 34 , 35 ].…”

Section: Discussionsupporting

confidence: 87%

Phase I study of aflibercept in combination with docetaxel in Japanese patients with advanced solid malignancies

et al. 2022

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Angiogenesis is a hallmark of cancer development. This study sought to determine the recommended dose of aflibercept, a recombinant fusion protein targeting VEGF-A, VEGF-B and placental growth factor (PlGF), combined with docetaxel in Japanese patients with advanced solid malignancies. This phase I study was planned to include 12 patients following a 3 + 3 algorithm to determine the maximum tolerated dose of aflibercept combined with docetaxel in patients with metastatic or unresectable solid tumors (trial registration: NCT00545246). Docetaxel (75 mg/m2 every 3 weeks or 60 mg/m2 after protocol amendment) was combined with escalating doses of aflibercept (2, 4 and 6 mg/kg every 4 weeks). Free and VEGF-bound aflibercept were measured to assess free aflibercept in excess of the VEGF-bound form. At the starting dose of the combination, 3 of 6 patients treated experienced febrile neutropenia. After reducing the docetaxel dose to 60 mg/m2 in step 2 and permitting therapeutic granulocyte colony-stimulating factor (G-CSF) use, 2 of 3 patients in both cohorts experienced febrile neutropenia. Five patients (42%) had a partial response and 4 patients had stable disease (33%). Free aflibercept in excess of the VEGF-bound form was not maintained at this dose level. The dose limiting toxicity (DLT) of aflibercept combined with docetaxel was febrile neutropenia, which occurred in 2 of 3 Japanese patients at the lowest aflibercept dose level (2 mg/kg) combined with docetaxel (60 mg/m2) and therapeutic G-CSF use. A recommended dose for further studies was not determined because of the DLT at the starting dose.

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Section: Discussionsupporting

confidence: 87%

Phase I study of aflibercept in combination with docetaxel in Japanese patients with advanced solid malignancies

et al. 2022

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“…Neutrophils have been shown to produce soluble factors like cytokines and chemokines that potentiate cancer cell-survival mechanisms and consequently inhibit response to therapy [ 6 , 7 , 36 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ]. This observation is underscored by clinical findings that show improved therapeutic response and prognosis in patients with mild chemotherapy-induced neutropenia [ 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 ]. The similar trend elucidated across these studies is notable since it suggests that inhibiting TANs may improve response to chemotherapy independent of other confounders.…”

Section: Neutrophils In Cancer Therapy Resistancementioning

confidence: 99%

Neutrophil Extracellular Traps in Cancer Therapy Resistance

Shahzad

Feng

et al. 2022

Cancers

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Neutrophils and their products are increasingly recognized to have a key influence on cancer progression and response to therapy. Their involvement has been shown in nearly every aspect of cancer pathophysiology with growing evidence now supporting their role in resistance to a variety of cancer therapies. Recently, the role of neutrophils in cancer progression and therapy resistance has been further complicated with the discovery of neutrophil extracellular traps (NETs). NETs are web-like structures of chromatin decorated with a variety of microbicidal proteins. They are released by neutrophils in a process called NETosis. NET-dependent mechanisms of cancer pathology are beginning to be appreciated, particularly with respect to tumor response to chemo-, immuno-, and radiation therapy. Several studies support the functional role of NETs in cancer therapy resistance, involving T-cell exhaustion, drug detoxification, angiogenesis, the epithelial-to-mesenchymal transition, and extracellular matrix remodeling mechanisms, among others. Given this, new and promising data suggests NETs provide a microenvironment conducive to limited therapeutic response across a variety of neoplasms. As such, this paper aims to give a comprehensive overview of evidence on NETs in cancer therapy resistance with a focus on clinical applicability.

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“…[20] Since hematologic toxicity, such as neutropenia, is a dose-dependent adverse event, patients who do not develop CIN may have received inadequate doses of the anticancer drugs or may be resistant to treatment. [21] Currently, the dose of anticancer drugs is administered to the patient based on body surface area (BSA) or creatinine clearance, [22] however, it has been suggested that BSA-based dosing calculations may be inadequate. [23] In two randomized trials of gastric and breast cancer, a trend toward improved progression-free and recurrence-free survival were observed in the latter group compared with the BSA-based dosing chemotherapy group and the group in which the dose of anticancer drugs was adjusted based on the incidence of adverse reactions, such as CIN.…”

Section: Discussionmentioning

confidence: 99%

Chemotherapy-induced neutropenia as a prognostic factor in patients with extensive-stage small cell lung cancer

Miyagi

Tsuji

Kawasakai

et al. 2023

Eur J Clin Pharmacol

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Chemotherapy-induced neutropenia (CIN) is a dose-limiting factor for cytotoxic chemotherapy, but recently, it was suggested that CIN contributes to prolonged survival. In this study, we examined the association between severe CIN and survival, and determined whether CIN affected survival in patients with extensive-stage small cell lung cancer (ED-SCLC).The medical records from 214 patients with ED-SCLC treated with etoposide or irinotecan in combination with cisplatin (EP/IP) between 2012 and 2016 were collected and retrospectively analyzed. Landmark analysis was performed at the end of cycle 4 and the relationship between severe CIN and survival was determined by a log-rank test. In addition, a multivariate analysis using COX proportional hazard model was performed to identify independent predictive factors. The Landmark analysis included 102 patients in the IP-group and 47 patients in the EPgroup. No signi cant difference was found between grade 0-3 and grade 4 neutropenia and overall survival (OS) in the EP-group. (P = 0.57). Contrariwise, for the IP patients, the median OS was 444 days for grade 0-3 and 633 days for grade 4 neutropenia, which was signi cantly longer for patients who developed grade 4 neutropenia (P = 0.03). Multivariate analysis adjusted for potential factors revealed that the development of grade 4 CIN was identi ed as a signi cant predictor of longer OS (hazard ratio[HR], 0.46; 95% con dence interval (CI), 0.26-0.81, P = 0.008). The results indicated that the development of severe CIN with IP therapy is associated with prolonged OS. Patients and treatmentsPatients who received standard doses of IP or EP as initial therapy for advanced and previously untreated SCLC were selected from the electronic medical record system of each participating institution. A total of 214 patients were selected and divided into two groups: those who received IP (n = 138) and those who received EP (n = 76). Clinical data and assessment of CINClinical data including patient characteristics and prognostic factors were collected from each hospital's electronic medical records. Hematologic toxicity was assessed based on the Common Terminology Criteria for Adverse Events, version 5.0 (CTCAE v5.0). CIN grade was determined based on the lowest neutrophil count for each patient recorded during rst-line treatment. The endpoint of the study was severe CIN survival. This was de ned as the time from the start date of cisplatin-based chemotherapy to the date of death or the last day of the follow-up period. Statistical analysisNeutropenia occurring during the treatment period was graded (grade 0-4) according to CTCAE v5.0.Survival curves for overall survival (OS) were generated for each grade of neutropenia using the Kaplan-Meier method and compared using the log-rank test. To analyze the effect of severe CIN development on

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Chemotherapy-induced neutropenia as a prognostic factor in patients with pancreatic cancer treated with gemcitabine plus nab-paclitaxel: a retrospective cohort study

Cited by 8 publications

References 27 publications

Phase I study of aflibercept in combination with docetaxel in Japanese patients with advanced solid malignancies

Phase I study of aflibercept in combination with docetaxel in Japanese patients with advanced solid malignancies

Neutrophil Extracellular Traps in Cancer Therapy Resistance

Chemotherapy-induced neutropenia as a prognostic factor in patients with extensive-stage small cell lung cancer

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