Impact of Five Prophylactic Filgrastim Schedules on Hematologic Toxicity in Early Breast Cancer Patients Treated With Epirubicin and Cyclophosphamide

Papaldo, Paola; Lopez, Massimo; Marolla, Paolo; Cortesi, Enrico; Antimi, Mauro; Terzoli, E.; Vici, Patrizia; Barone, Carlo; Ferretti, Gianluigi; Cosimo, Serena Di; Carlini, Paolo; Nisticò, Cecilia; Conti, Francesca; Lauro, Luigi Di; Botti, Claudio; Filippo, Francox Di; Fabi, Alessandra; Giannarelli, Diana; Calabresi, F.

doi:10.1200/jco.2005.03.099

Cited by 94 publications

(52 citation statements)

References 69 publications

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“…However, use of CTX is often restricted due to cytotoxic effects that result from formation of reactive metabolites that alkylate DNA and proteins, and also produce cross-links. Among the adverse side-effects that often subsequently result are nausea, mucosal ulceration, vomiting, pulmonary fibrosis, skin pigmentation, hematopoietic suppression, nephrotoxicity, urotoxicity, and hepatotoxicity (Amudha et al, 2007;Kiuchi et al, 2009;Papaldo et al, 2005). To combat this, CTX is currently used in combination with other protective agents with the purpose of reducing the adverse toxic effects.…”

Section: Introductionmentioning

confidence: 99%

Acacia ferrugineainhibits cyclophosphamide-induced immunosuppression and urotoxicity by modulating cytokines in mice

Sakthivel

Guruvayoorappan

2014

Journal of Immunotoxicology

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Cyclophosphamide (CTX), commonly used as an anti-neoplastic drug, can cause adverse sideeffects including immunotoxicity and urotoxicity. Increasingly, plants have become sources of therapeutics that can help to restore host immunity to normal. In this study, Acacia ferruginea was assessed for an ability to protect mice against/mitigate CTX-induced toxicity. Coadministration of an extract of A. ferruginea (10 mg/kg BW, IP daily) for 10 consecutive days reduced CTX (25 mg/kg BW, IP daily)-induced toxicity. Apart from improvements in bladder and small intestine morphology, there was marked improvement in anti-oxidant (glutathione) levels in the bladder, suggesting a role for the anti-oxidant in reducing CTX-induced urotoxicity. Moreover, use of the extract significantly increased total leukocyte counts and bone marrow cellularity/-esterase activity in CTX-treated mice which suggested a protective effect on the hematopoietic system. Co-treatment with the extract also prevented decreases in organ (liver, kidney, spleen, thymus) weight as well as body weight, thereby seemingly lessening the potential impact of CTX on the host immune system. Further, CTX-induced increases in serum aspartate transanimase, alanine transaminase, and alkaline phosphatase were reversed by extract co-treatment, as were alterations in in situ formation/release of interferon (IFN)-, interleukin (IL)-2, granulocyte-macrophage colony stimulating factor (GM-CSF), and tumor necrosis factor (TNF)-. Overall, this study indicated there were some protective effects from use of an extract of A.ferruginea against CTX-induced toxicities, in part through modulation of levels of anti-oxidants and pro-inflammatory cytokines.

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Section: Introductionmentioning

confidence: 99%

Acacia ferrugineainhibits cyclophosphamide-induced immunosuppression and urotoxicity by modulating cytokines in mice

Sakthivel

Guruvayoorappan

2014

Journal of Immunotoxicology

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“…Despite these recommendations, the literature data confirm that the scheduling of rHu-G-CSF is extremely variable among different authors ranging from 2 days (19) to 14 days (20) or until recovery of 10,000 neutrophils/lL (21,22). In the Papaldo et al (13) study, one group of patients was treated prophylactically with 300 lg on the 8th and 12th day after chemotherapy. No differences were observed in the rate of FN in this group, compared with the more intensive treatments.…”

Section: Discussionmentioning

confidence: 99%

“…administration of G-CSF at the 8th and 12th day after chemotherapy, may equally prevent neutropenia and chemotherapy delay (13).…”

mentioning

confidence: 99%

Predictive value of hematological and phenotypical parameters on postchemotherapy leukocyte recovery

Bononi¹,

Lanza

Ferrari

et al. 2009

Cytometry Part B Clinical

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Background: Grade IV chemotherapy toxicity is defined as absolute neutrophil count <500/lL. The nadir is considered as the lowest neutrophil number following chemotherapy, and generally is not expected before the 7th day from the start of chemotherapy. The usual prophylactic dose of rHu-G-CSF (Filgrastim) is 300 lg/day, starting 24-48 h after chemotherapy until hematological recovery. However, individual patient response is largely variable, so that rHu-G-CSF doses can be different. The aim of this study was to verify if peripheral blood automated flow cytochemistry and flow cytometry analysis may be helpful in predicting the individual response and saving rHu-G-CSF.Methods: During Grade IV neutropenia, blood counts from 30 cancer patients were analyzed daily by ADVIA 120 automated flow cytochemistry analyzer and by Facscalibur flow cytometer till the nadir. ''Large unstained cells'' (LUCs), myeloperoxidase index (MPXI), blasts, and various cell subpopulations in the peripheral blood were studied. At nadir rHu-G-CSF was started and 81 chemotherapy cycles were analyzed. Cycles were stratified according to their number and to two dose-levels of rHuG-CSF needed to recovery (300-600 vs. 900-1200 lg) and analyzed in relation to mean values of MPXI and mean absolute number of LUCs in the nadir phase. The linear regressions of LUCs % over time in relation to two dose-levels of rHu-G-CSF and uni-multivariate analysis of lymphocyte subpopulations, CD34 1 cells, MPXI, and blasts were also performed.Results: In the nadir phase, the increase of MPXI above the upper limit of normality (>10; median 27.7), characterized a slow hematological recovery. MPXI levels were directly related to the cycle number and inversely related to the absolute number of LUCs and CD34

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“…33 Less frequent dosing of daily G-CSF through a cycle has been studied in the setting of patients receiving relatively lower myelosuppressive chemotherapy, consisting of an anthracycline and cytoxan for breast cancer. 34 Intermittent schedules were not significantly worse in daily dosing.…”

Section: Prophylaxis Of Chemotherapy-induced Neutropoeniamentioning

confidence: 96%

Management of Chemotherapy-induced Neutropoenia

Schwartzberg¹

2008

European Oncology &Amp; Haematology

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During the past several years, a number of novel targeted anticancer drugs have been integrated into clinical practice. Despite the efficacy and variety of new agents, traditional myelosuppressive chemotherapy remains the backbone of cancer treatment. In addition, the new biologicals often increase myelotoxicity when added to standard chemotherapy regimens.Therefore, myelosuppression remains the most common toxicity encountered in the oncology clinic today and this complication is likely to remain a serious problem indefinitely. Chemotherapy-induced neutropoenia (CIN) is defined clinically as an absolute neutrophil count (ANC) of <1.0x10 9 /l, at which point the risk of infection begins to rise. This risk is related both to the depth and duration of neutropoenia. 1 An ANC below 0.5x10 9 /l is therefore considered severe neutropoenia (SN) and febrile neutropoenia (FN) is defined as a temperature >38.2ºC on two determinations with an ANC <0.5x10 9 /l, which indicates a high likelihood of a localised or systemic infection. FN requires prompt intervention with broad spectrum antibiotics until endogenous recovery of the bone marrow occurs. Subsequent evaluation of the MASCC index has validated the prognostic accuracy of the score in other patient populations. 5 The tool has proven clinical utility in allowing patients at low risk to be treated successfully with oral antibiotics and be followed as outpatients. 6,7 Attempts to incorporate blood inflammatory marker analysis into the clinical scale did not add to the predictive value of the MASCC score. 8 A risk-adapted strategy utilising the MASCC index allows a significant fraction of low-risk patients to be treated in the outpatient setting when follow-up is careful and adherence to medical care is high. 9 Nonetheless, the majority of patients with FN do require at least some inpatient observation and treatment with intravenous antibiotics. The costs associated with FN and its treatment are substantial and are not limited to the direct cost of hospitalisations. It is likely that even separating out low-risk patients for outpatient treatment will not have a great impact on costs, which are driven mostly by the fraction of patients who have severe complications. 10 Health systems may therefore be obligated to expend increased resources caring for patients with FN.Risk of SN and FN from chemotherapy depends on several factors, most importantly the myelosuppressive intensity of the chemotherapy regimen utilised. One way to reduce the risk of CIN is to reduce the drug dosage delivered. However, substantial direct and retrospective evidence suggests that reduction in relative dose intensity is deleterious in terms of disease-free outcome and overall survival in the curative and perhaps life-prolonging indications for chemotherapy. 11,12 CIN is a common cause of chemotherapy dose delay and dose reduction, 13 and prolonged recovery from FN may compromise subsequent cycle delivery of full dose on schedule. Colony-stimulating Factors for Chemotherapy-induced NeutropoeniaAn alte...

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Impact of Five Prophylactic Filgrastim Schedules on Hematologic Toxicity in Early Breast Cancer Patients Treated With Epirubicin and Cyclophosphamide

Cited by 94 publications

References 69 publications

Acacia ferrugineainhibits cyclophosphamide-induced immunosuppression and urotoxicity by modulating cytokines in mice

Acacia ferrugineainhibits cyclophosphamide-induced immunosuppression and urotoxicity by modulating cytokines in mice

Predictive value of hematological and phenotypical parameters on postchemotherapy leukocyte recovery

Management of Chemotherapy-induced Neutropoenia

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