A multicenter prospective phase II randomized trial of epirubicin/vinorelbine versus pegylated liposomal doxorubicin/vinorelbine as first-line treatment in advanced breast cancer. A GOIM study

Vici, Patrizia; Colucci, Giuseppe; Giotta, Francesco; Sergi, Domenico; Filippelli, Gianfranco; Perri, Pasquale; Botti, Claudio; Vizza, Enrico; Carpino, Armando; Pizzuti, Laura; Latorre, Agnese; Giannarelli, Diana; Lopez, Massimo; Lauro, Luigi Di

doi:10.1186/1756-9966-30-39

Cited by 20 publications

(10 citation statements)

References 38 publications

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“…The changes in the blood cells especially erythrocytes, platelets, and leucocyte count were all DOX dose dependent and were consistent with the findings reported by Manno et al [ 5 ]; Tacar et al [ 51 ], which could be attributed to the known bone marrow suppressive effect of DOX and iron-DOX interaction, thus causing RBC membrane rupture as previously reported by Vici et al [ 52 ] and Pahouja et al [ 53 ] since DOX did not limit its effects not only to cancer cell alone but also to proliferating haematopoietic cells.…”

Section: Discussionsupporting

confidence: 91%

Toxicity and Safety Evaluation of Doxorubicin-Loaded Cockleshell-Derived Calcium Carbonate Nanoparticle in Dogs

Danmaigoro

Selvarajah

Noor

et al. 2018

Advances in Pharmacological Sciences

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Doxorubicin (DOX) is a potent anticancer agent with cytotoxic effects which limit its clinical usage. This effect is due to its nonselective nature causing injury to the cells as a result of reactive free oxygen radical's release. Cockleshell-derived calcium carbonate nanoparticle (CS-CaCO3NP) is a pH-responsive carrier with targeted delivery potentials. This study aimed at evaluating the toxicity effects of repeated dose administration of DOX-loaded CS-CaCO3NP in healthy dogs. Fifteen dogs with an average body weight of 15 kg were randomized equally into 5 groups. Dogs were subjected to 5 doses at every 3-week interval with (i) normal saline, (ii) DOX, 30 mg/m2, and the experimental groups: CS-CaCO3NP-DOX at (iii) high dose, 50 mg/m2, (iv) clinical dose, 30 mg/m2, and (v) low dose, 20 mg/m2. Radiographs, electrocardiography, and blood samples were collected before every treatment for haematology, serum biochemistry, and cardiac injury assessment. Heart and kidney tissues were harvested after euthanasia for histological and ultrastructural evaluation. The cumulative dose of DOX 150 mg/m2 over 15 weeks revealed significant effects on body weight, blood cells, functional enzymes, and cardiac injury biomarkers with alterations in electrocardiogram, myocardium, and renal tissue morphology. However, the dogs given CS-CaCO3NP-DOX 150 mg/m2 and below did not show any significant change in toxicity biomarker as compared to those given normal saline. The study confirmed the safety of repeated dose administration of CS-CaCO3NP-DOX (30 mg/m2) for 5 cycles in dogs. This finding offers opportunity to dogs with cancer that might require long-term administration of DOX without adverse effects.

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Section: Discussionsupporting

confidence: 91%

Toxicity and Safety Evaluation of Doxorubicin-Loaded Cockleshell-Derived Calcium Carbonate Nanoparticle in Dogs

Danmaigoro

Selvarajah

Noor

et al. 2018

Advances in Pharmacological Sciences

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“…In the current scenario, our reporting is of limited meaning and mainly confined to the particularly high rate of pCR and lack of development of significant cardiotoxicity. In an optimistic view, we may at least partly explain the efficacy rates by the use of epirubicin at a dose of 120 mg/m 2 per cycle instead than the canonical dose of 90 mg/m 2 , since a dose‐response effect has been more clearly demonstrated with epirubin than doxorubicin (Vici et al, ). In addition, the choice of a less cardiotoxic anthracycline‐analog such as epirubicin may have conditioned the lack of development of any significant cardiotoxicity, along with the cumulative epirubicin dose not exceeding 480 mg/m 2 , the strict criteria applied for patient selection, the low median age, and the absence of any previous treatment.…”

Section: Discussionmentioning

confidence: 99%

Neoadjuvant Sequential Docetaxel Followed by High‐Dose Epirubicin in Combination With Cyclophosphamide Administered Concurrently With Trastuzumab. The DECT Trial

Pizzuti¹,

Barba

Giannarelli³

et al. 2016

J. Cell. Physiol.

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To report the results of the DECT trial, a phase II study of locally advanced or operable HER2-positive breast cancer (BC) treated with taxanes and concurrent anthracyclines and trastuzumab. Eligible patients (stage IIA-IIIB HER2-positive BC, 18-75 years, normal organ functions, ECOG 1, and left ventricular ejection fraction (LVEF) !55%) received four cycles of neoadjuvant docetaxel, 100 mg/m 2 intravenously, plus trastuzumab 6 mg/kg (loading dose 8 mg/kg) every 3 weeks, followed by four 3-weekly cycles of epirubicin 120 mg/m 2 and cyclophosphamide, 600 mg/m 2 , plus trastuzumab. Primary objective was pathologic complete response (pCR) rate, defined as ypT0/is ypN0 at definitive surgery. We enrolled 45 consecutive patients. All but six patients (13.3%) completed chemotherapy and all underwent surgery. pCR was observed in 28 patients (62.2%) overall and in 6 (66.7%) from the inflammatory subgroup. The classification and regression tree analysis showed a 100% pCR rate in patients with BMI !25 and with hormone negative disease. The median follow up was 46 months (8-78). Four-year recurrencefree survival was 74.7% (95%CI, 58.2-91.2). Seven patients (15.6%) recurred and one died. Treatment was well tolerated, with limiting toxicity being neutropenia. No clinical cardiotoxicity was observed. Six patients (13.4%) showed a transient LVEF decrease (<10%). In one patient weThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.L. Pizzuti and M. Barba contributed equally to this work. Conflicts of interest:The authors declare that they have no conflict of interest.

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“…In our study, doxorubicin administration resulted in anemia, leukopenia and thrombocytopenia due to the suppressive effects of doxorubicin on the bone marrow, with only partial reversibility in the high‐dose animals. Hematologic toxicity as a result of bone marrow suppression is a well‐known side effect of doxorubicin treatment and has been reported in humans (Vici et al ., ) as well as in animal models (Desai et al ., ). Such changes manifest as a decline in the red blood cell lineage, including a decreased red blood cell count, hematocrit and hemoglobin levels (Bertazzoli et al ., , Herman et al ., , Molyneux et al ., , Panis et al ., ).…”

Section: Discussionmentioning

confidence: 99%

The minipig as a new model for the evaluation of doxorubicin‐induced chronic toxicity

Manno¹,

Grassetti²,

Oberto³

et al. 2015

J of Applied Toxicology

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Doxorubicin can cause life-threatening toxic effects in several organs, with cardiotoxicity being the major concern. Although a large number of animal models have been utilized to study doxorubicin toxicity, several restrictions limit their use. Since the Göttingen minipig is an accepted species for non-clinical safety assessment and translation to man, we aimed at exploring its use as a non-rodent animal model for safety assessment and regulatory toxicity studies using doxorubicin. Three groups of three males and three females adult Göttingen minipigs received 1.5 mg kg(-1) , 3/2.3 mg kg(-1) or vehicle at intervals of 3 weeks for 7 cycles. Doxorubicin treatment resulted in a dose-related decrease in the erythrocytes, hemoglobin and hematocrit count, accompanied by leukopenia and thrombocytopenia. Bone marrow smears revealed dose-related hypocellularity. Urea and creatinine levels were elevated in treated animals, associated with proteinuria and hematuria. Histopathological evaluation detected nephropathy and atrophy of hematopoietic tissues/organs, mucosa of the intestinal tract and male genital tract. Cardiac lesions including chronic inflammation, endocardial hyperplasia, hemorrhage and myxomatous changes were evident in hematoxylin and eosin stains, and evaluation of semi-thin sections showed the presence of dose-related vacuolation in the atrial and ventricular cardiomyocytes. Cardiac troponin levels were increased in the high-dose group, but there was no direct correlation to the severity of the histopathological lesions. This study confirms that the Göttingen minipig has a comparable toxicity profile to humans and considering its anatomical, physiological, genetic and biochemical resemblance to humans, it should be considered as the non-rodent species of choice for studies on doxorubicin toxicity. Copyright © 2015 John Wiley & Sons, Ltd.

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A multicenter prospective phase II randomized trial of epirubicin/vinorelbine versus pegylated liposomal doxorubicin/vinorelbine as first-line treatment in advanced breast cancer. A GOIM study

Cited by 20 publications

References 38 publications

Toxicity and Safety Evaluation of Doxorubicin-Loaded Cockleshell-Derived Calcium Carbonate Nanoparticle in Dogs

Toxicity and Safety Evaluation of Doxorubicin-Loaded Cockleshell-Derived Calcium Carbonate Nanoparticle in Dogs

Neoadjuvant Sequential Docetaxel Followed by High‐Dose Epirubicin in Combination With Cyclophosphamide Administered Concurrently With Trastuzumab. The DECT Trial

The minipig as a new model for the evaluation of doxorubicin‐induced chronic toxicity

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