Publications (7)8.58 Total impact
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Article: Chemotherapy-induced anemia in breast cancer patients treated with pegfilgrastim-supported dose-dense regimens.
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ABSTRACT: The primary use of recombinant granulocyte colony-stimulating factors has reduced the incidence of febrile neutropenia during dose-dense adjuvant/neoadjuvant chemotherapy programs for breast cancer. Otherwise, in this population, filgrastim seems to worse chemotherapy-induced anemia, especially when administered with prolonged schedules that induced leukocytosis. No exhaustive data are available about the effect of long-lasting formulation of filgrastim (pegfilgrastim) on hemoglobin levels. We retrospectively analyzed the data regarding hemoglobin level and leukocyte count of 38 breast cancer patients treated with dose-dense anthracycline and/or taxane-based chemotherapy with pegfilgrastim support, both in adjuvant and in neoadjuvant settings. Mean hemoglobin levels progressively decreased throughout the treatment (without correlation with both the schedule of chemotherapy and the patient's age) but only two patients developed mild anemia. No significant correlation was found between the degree of leukocytosis and the hemoglobin decrease. These data suggest that pegfilgrastim, per se, doesn't seem to worse chemotherapy-induced anemia. This fact may be at least in part explains by its "balanced" impact on hematopoietic recovery during dose-dense chemotherapy.Clinical and Experimental Medicine 10/2009; 10(2):135-8. · 1.58 Impact Factor -
Article: Biological effects of pegfilgrastim on circulating neutrophils in breast cancer patients undergoing dose-dense chemotherapy.
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ABSTRACT: Pegfilgrastim is a covalent conjugate of filgrastim and polyethylene glycol that has proved to be effective in supporting myelopoiesis during chemotherapy. Since very limited information is available on the biological effects of pegfilgrastim on neutrophils exposed to chemotherapy, we analyzed the following parameters in neutrophils of patients undergoing dose-dense chemotherapy for breast cancer: apoptosis, by a TUNEL technique; actin polymerization, using FITC-labeled phalloidin, and alkaline phosphatase activity by cytochemistry. Peripheral blood buffy coat smears were obtained before starting treatment and immediately before each chemotherapy course. After pegfilgrastim stimulation we observed the following: (1) stability of the absolute neutrophil count for the whole duration of treatment and no infectious events; (2) a reduction in the neutrophil constitutive apoptosis rate in comparison with that observed in control patients treated with standard chemotherapy courses with no growth factor support; (3) persistent abnormalities of actin assembly in neutrophils, indicative of changes in cytoskeletal organization, and (4) a significant increase in the activity of leukocyte alkaline phosphatase, a sensitive marker of the later stages of neutrophil maturation. In conclusion, these results suggest that pegfilgrastim improves the neutrophil functions in patients exposed to chemotherapy by inhibition of constitutive apoptosis, thereby prolonging the survival of these cells.Oncology 11/2008; 75(3-4):237-44. · 2.27 Impact Factor -
Article: Weekly docetaxel and gemcitabine following docetaxel plus epirubicin or vinorelbine as first-line treatment of metastatic breast cancer: results of a multicenter phase II study.
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ABSTRACT: Sequential docetaxel and gemcitabine following initial docetaxel plus epirubicin or vinorelbine association could be worthwhile as first-line treatment of metastatic breast cancer. Fifty-eight patients entered a phase II study that included two sequential phases. In the first phase, 36 and 22 patients previously unexposed or exposed to adjuvant anthracyclines received the association of docetaxel (75 mg/m2, day 1) with epirubicin (75 mg/m2, day 1) or vinorelbine (20 mg/m2, days 1 and 5), respectively, every 21 days for 4 courses. In the second phase, patients who had a response (R) or stable disease (SD) received docetaxel (35 mg/m2) and gemcitabine (800 mg/m2) on days 1, 8 and 15 every 28 days for 4 courses. In the first phase, grade > or = III neutropenia occurred in 51% and 37% of patients during docetaxel-epirubicin and docetaxel-vinorelbine, respectively. In the second phase, it occurred in the 27% and 15% of patients initially treated with docetaxel-epirubicin and docetaxel-vinorelbine, respectively. On an intention to treat basis, the complete (CR) + partial response (PR) rate to the first phase was 71%, and 22% of patients had SD, without a significant difference between the docetaxel-epirubicin and docetaxel-vinorelbine arms. After the second phase, the CR + PR rate was 65%, and 14% of patients had SD. Median time to progression and survival were 12.1 and 22.0 months, respectively, without a significant difference between patients initially treated with docetaxel-epirubicin and docetaxel-vinorelbine. Following an initial docetaxel-based treatment, weekly docetaxel and gemcitabine maintains high percentages of R and SD, with improved toxicity. Survival was similar in patients previously untreated and treated with adjuvant anthracyclines.Tumori 92(1):6-12. · 0.86 Impact Factor -
Article: Bisphosphonates in oncology: physiopathologic bases and clinical activity.
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ABSTRACT: Osteoclastic activation is the ultimate way of bone resorption in neoplasia, induced by the combined effects of tumor-secreted humoral factors (especially parathyroid hormone-related peptides) and osteoclastic-osteoblastic interaction. Bisphosphonates inhibit the osteoclast activity and reduce bone resorption and are a valuable supportive measure for bone disease of neoplasms. Experimental models also suggest an activity of bisphosphonates against cancer cells. Controlled studies, especially in advanced breast cancer and multiple myeloma, indicate different effectiveness against the distinct skeletal-related events. Intravenous clodronate and, especially, pamidronate and zoledronate are the first-choice drugs for hypercalcemia, and they play a significant role in reducing metastatic bone pain. Their prolonged use delays, without hampering, the progression of bone disease, including the appearance of osteolysis and the occurrence of pathologic fractures. This effect is probably more valuable when bisphosphonates are administered early in the course of the disease. The evidence that adjuvant bisphosphonates improve survival needs to be confirmed in ongoing studies. Although poorly absorbed by the gastrointestinal tract, oral bisphosphonates are effective in preventing and treating cancer-induced osteoporosis in long-living patients with operable breast cancer. At present, there is little hope that newer bisphosphonates are more effective than those currently used.Tumori 89(3):223-36. · 0.86 Impact Factor -
Article: In vivo biological effects of pegfilgrastim after myelosuppressive chemotherapy in breast cancer.
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ABSTRACT: No exhaustive data are available on the in vivo biological effects of pegfilgrastim utilized in dose-dense chemotherapy (CT). The cytokinetic effects exerted in a multicyclic CT program by this cytokine on CD34+/38+ peripheral blood (PB) progenitor cells was the focus of this study. PB samples from 19 breast cancer patients treated with 4 courses of docetaxel and epirubicin followed by pegfilgrastim were studied. The absolute number of CD34+/38+ circulating progenitor cells (CPCs) along with the percentage undergoing GO/G1, S and G2-M phases of the cell cycle or showing apoptotic features, were evaluated at baseline, after the first and before the fourth CT course using a dedicated flow cytometric technique. Pegfilgrastim, after CT, exerted stimulatory effects on the cell cycle status of PB CD34+/38+ CPCs, at the same time protecting them from apoptosis. This was particularly evident 7 days after administration and tended to decrease one week later, without additional cytokinetic changes during the subsequent CT courses.Anticancer research 27(5A):3399-402. · 1.73 Impact Factor -
Article: Single-dose palonosetron and dexamethasone in preventing nausea and vomiting induced by moderately emetogenic chemotherapy in breast and colorectal cancer patients.
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ABSTRACT: Palonosetron, a unique second-generation 5-HT3 receptor antagonist, has been demonstrated to control emesis related to chemotherapy-induced nausea and vomiting (CINV). The aim of this study was to evaluate the efficacy and tolerability of palonosetron followed by a single dose of dexamethasone in patients with breast cancer (BC) or colorectal cancer (CRC) receiving moderate emetogenic chemotherapy (MEC). Chemotherapy-naive BC and CRC patients were given MEC as adjuvant or first-line treatment. Palonosetron (0.25 mg IV) and dexamethasone (8 mg IV) were administered before chemotherapy on day 1. The primary endpoint was complete response (CR; no vomiting and no use of rescue medication) during the overall study period (days 1-5). The antiemetic response was evaluated during the acute (day 1) and delayed (days 2-5) phases. Sixty-eight patients were enrolled (median age 61 years, 56 females; BC = 40, CRC = 28). CR was observed in 46 of 68 patients (67.6%), while CR during the acute and delayed phases was 75.0% in each cancer group. The antiemetic regimen was well tolerated. A single administration of palonosetron and dexamethasone on day 1 in BC and CRC patients adequately controls CINV during the entire period of emetic risk.Tumori 97(3):362-6. · 0.86 Impact Factor -
Article: Effect of peg-filgrastim-supported dose-dense adjuvant chemotherapy on the peripheral blood leukocyte phenotype in breast cancer patients.
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ABSTRACT: The aim of this study was to evaluate the effect of dose-dense adjuvant chemotherapy regimens with peg-filgrastim support on the phenotype of peripheral blood leukocytes in breast cancer patients. We evaluated the leukocyte phenotype of 14 patients aged 46-67 years undergoing 4 courses of chemotherapy with either epirubucin/cyclophosphamide (n=7) or 5-fluorouracil/epirubucin/cyclophosphamide (n=7) followed by 4 courses of taxol supported by peg-filgrastim (6 mg) administered 72 h after each chemotherapy course. The overall leukocyte number significantly increased from the first treatment course, while total lymphocytes tended to decrease with a negative peak following the 6th course (p=0.03). B (CD19+, CD20+) and early B lymphocyte subsets (CD20+/CD38+) significantly decreased during treatment (p<0.05), while T lymphocyte subsets did not show significant changes, except a decrease in T helper (CD4+) cells. Immature T lymphocytes (CD4+/CD8+ subset), dendritic cells (CD11c+) and NK cells (CD56+) increased with respect to the baseline. Our results suggest that dose-dense chemotherapy programs with the support of peg-filgrastim did not significantly impair the immune system of breast cancer patients and allowed for a rapid restoration of most immune competent cells. These observations may have important clinical implications with a view to vaccination or other immunotherapeutic approaches to solid tumours.Molecular Medicine Reports 2(1):85-8. · 0.42 Impact Factor
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Institutions
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2009
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Policlinico San Matteo Pavia Fondazione IRCCS
Pavia, Lombardy, Italy
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