0000000000019243
AUTHOR
Biagio Agostara
Adjuvant anastrozole versus exemestane versus letrozole, upfront or after 2 years of tamoxifen, in endocrine-sensitive breast cancer (FATA-GIM3): a randomised, phase 3 trial
Background: Uncertainty exists about the optimal schedule of adjuvant treatment of breast cancer with aromatase inhibitors and, to our knowledge, no trial has directly compared the three aromatase inhibitors anastrozole, exemestane, and letrozole. We investigated the schedule and type of aromatase inhibitors to be used as adjuvant treatment for hormone receptor-positive early breast cancer. Methods: FATA-GIM3 is a multicentre, open-label, randomised, phase 3 trial of six different treatments in postmenopausal women with hormone receptor-positive early breast cancer. Eligible patients had histologically confirmed invasive hormone receptor-positive breast cancer that had been completely remov…
Expression Levels and Clinical-Pathological Correlations of HER2/neu in Primary and Metastatic Human Breast Cancer
In this retrospective study we assessed the expression of the HER2/neu oncogene product in a series of 574 consecutive breast cancer cases, all recruited at the Maurizio Ascoli Cancer Center of Civico Hospital, in Palermo, between January 1998 and June 2003. The HER2/neu expression was evaluated using immunohistochemistry and scored from 0 to +3 as per FDA recommendations. The HER2/neu expression levels were related to the clinical-pathological features of the disease, including tumor size, nodal and menopausal status, estrogen and progesterone receptors, and hormonal or chemotherapeutic treatment. In 108 patients with a follow-up period of 3 years or more, the HER2/neu expression was also …
Gemcitabine plus vinorelbine in stage IIIB or IV non-small cell lung cancer (NSCLC): A multicentre phase II clinical trial
Abstract A phase II study in patients with stage IIIB/IV non-small cell lung cancer (NSCLC) was carried out to evaluate the clinical activity and toxicity of the chemotherapeutic combination of gemcitabine+vinorelbine (GEM/VNR). Forty-five patients (40 male, 5 female) with a median age of 67 years (range 37–73) and a median ECOG performance status of 1 (range 0–2) were enrolled into the trial. Twenty patients had stage IIIB (two positive supraclavicular nodes and 20 cytologically positive pleural effusion), and 25 had stage IV NSCLC. GEM 1000 mg/m 2 diluted in 250 cc 3 of normal saline was administered iv on days 1, 8, and 15, while VNR was given 30 mg/m 2 on days 1 and 8 every 4 weeks. The…
Sex steroids, carcinogenesis, and cancer progression
The relationship between sex steroids and cancer has been studied for more than a century. Using an original intact cell analysis, we investigated sex steroid metabolism in a panel of human cancer cell lines, either hormone responsive or unresponsive, originating from human breast, endometrium, and prostate. We found that highly divergent patterns of steroid metabolism exist and that the catalytic preference (predominantly reductive or oxidative) is strictly associated with the steroid receptor status of cells. We explored intra-tissue concentrations and profiles of estrogens in a set of human breast tumors as compared to normal mammary tissues, also in relation to their estrogen receptor s…
Efficacy and Safety of Cetuximab/Irinotecan in Chemotherapy-Refractory Metastatic Colorectal Adenocarcinomas: A Clinical Practice Setting, Multicenter Experience
This study was designed to evaluate the efficacy and safety of irinotecan/cetuximab administered as third- or fourth-line therapy in a retrospective series of patients with metastatic colorectal cancer refractory to oxaliplatin and irinotecan. Patients and Methods: Most patients (90%) had been previously treated with adjuvant 5-fluorouracil/leucovorin, and all had received oxaliplatin-based regimens before receiving irinotecan- based second-line treatment. Sixty patients with irinotecan-refractory colorectal cancer received a regimen comprising weekly irinotecan 120 mg/m 2 as a 1-hour intravenous infusion and cetuximab 400 mg/m 2 infused over 2 hours as the initial dose and 250 mg/m 2 infus…
Mitomycin 'C' and vinorelbine as second line chemotherapy for metastatic breast carcinoma
Aims and background Patients with metastatic breast carcinoma resistant to first line chemotherapy may require further treatment. Results o second line chemotherapy are still largerly unsatisfactory. For this reason a phase II study on the combination of mitomycin C and vinorelbine was carried out. Methods Forty patients with anthracycline pretreated metastatic breast cancer were treated with a combination of mitomycin C 10 mg/m2 i.v. on day 1, and vinorelbine 25 mg/m2 i.v. on days 1 and 8. This cycle was repeated every 28 days. Responses were evaluated according to the WHO criteria. Results A major objective response was recorded in 16 cases (40%; 95% confidence limits 32%-48%), with 2 pat…
Androgen metabolism and biotransformation in nontumoral and malignant human liver tissues and cells
There is indirect multiple evidence that hints at a potential role of sex steroids in development and progression of human hepatocellular carcinoma (HCC). In the present study, we have investigated androgen metabolism in a panel of human liver cancer cell lines (HA22T, Huh7, HepG2) and in normal, cirrhotic and malignant human liver tissues aiming to dissect the potential impact of individual enzyme activities and their products in normal and diseased human liver, both in vivo and in vitro. Using our intact cell analysis we were able to assess rates and pathways of androgen metabolism in living conditions. Overall, incubation of cultured cells or tissue minces with either testosterone (T) or…
Abstract 1726: Estrogen implication in human hepatocellular carcinoma is associated with changes in estrogen receptors and aromatase expression
Abstract There is evidence that hints at a potential role of sex steroids in development and progression of human hepatocellular carcinoma (HCC). Previous studies have revealed that estrogen receptors (ER) are expressed in primary HCC. However, the use of antiestrogens has failed to improve disease-free and overall survival of patients. In the present study we have investigated aromatase-driven estrogen formation in nontumoral and malignant human liver tissues and cells, also in relation to the expression of ERα, ERβ, and their splicing variants, aiming to get insights into the potential role of estrogens and the underlying mechanism(s) in human HCC. Chromatographic and exon-specific RT-PCR…
A phase I-II study of cyclophosphamide, epidoxorubicin, levofolinic acid/5-fluorouracil and recombinant human granulocyte colony stimulating factor in metastatic breast carcinoma.
Thirty patients with measurable metastatic breast carcinoma were treated with a combination of cyclophosphamide 600 mg/m2 on day 1, levofolinic acid 100 mg/m2 plus 5-fluorouracil 375 mg/m2 on days 1-3, and epidoxorubicin (EDXR) in three refracted doses on days 1-3 with G-CSF rescue for 10 days. In the phase I part of the study, groups of 3 patients received EDXR 20, 25, 30, 35, and 40 mg/m2/day until the dose limiting toxicity (DLT) was reached. At the dose of 40mg/m2/day prolonged grade 4 leukopenia, severe proctitis, and grade 3 diarrhea represented the DLT. All subsequent partients were treated at the maximal tolerated dose of EDXR (35 mg/m2/day). In the group of 18 patients treated at 3…
Expression of Wild-Type and Variant Estrogen Receptor Alpha in Liver Carcinogenesis and Tumor Progression.
Although estrogen receptors (ERs) are expressed in human hepatocellular carcinoma (HCC), several clinical trials have failed to demonstrate the efficacy of antiestrogen treatment in HCC patients. Recently, the identification of several ER splicing variants has enlightened the complex nature of estrogen signaling in peripheral tissues; this may help understanding estrogen role in either nontumoral or malignant nonclassical target organs, including liver. In this work we have investigated mRNA expression of wild-type and splice variants of ERα in nontumoral, cirrhotic, and malignant human liver, as well as in HCC cell lines, using an exon-specific reverse transcription polymerase chain reacti…
Vinorelbine, cisplatin, and 5-fluorouracil as initial treatment for previously untreated, unresectable squamous cell carcinoma of the head and neck
BACKGROUND The combination of vinorelbine (VNR), cisplatin (CDDP), and 5-fluorouracil (5-FU) has previously been shown to be active in recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCHNC). This multicenter Phase II study was carried out with the aim of evaluating the effectiveness of this combination in patients with previously untreated, unresectable locally advanced SCHNC. METHODS Sixty patients with previously untreated, unresectable SCHNC were treated with CDDP 80 mg/m2 on Days 1, 5-FU 600 mg/m2 as a 4-hour infusion on Days 2-5, and VNR 25 mg/m2 iv bolus on Days 2 and 8. There were 15 patients with laryngeal carcinoma, 19 patients with oropharyngeal carcinoma…
Target therapy in HER2-overexpressing breast cancer patients.
The development of new therapeutic strategies, such as monoclonal antibodies directed against human epidermal growth factor receptor-2 (HER2), has offered new hopes for women with early breast cancer whose tumors overexpress HER2. We retrospectively analyzed the population-based data of Breast Cancer Registry of Palermo in 2004-2006, and selected 1401 invasive breast cancer cases, nonmetastatic at diagnosis, having HER2/neu oncogene expression determined. We have correlated this information to age, tumor stage at diagnosis (TNM), nodal involvement, and receptor status (ER and PgR). Survival analysis was conducted dividing the patients in two different groups according to date of diagnosis: …
Doxorubicin-docetaxel sequential schedule: results of front-line treatment in advanced breast cancer.
<i>Objective:</i> We conducted a multi-institutional phase II study to evaluate the tolerability and activity of a sequential schedule of treatment with doxorubicin and docetaxel in chemotherapy-naive women with advanced breast cancer. <i>Methods:</i> A total of 73 patients with PS (ECOG) 0–2, aged <70 years and adequate bone marrow, renal, liver and cardiac functions were included in the study (13 stage III B and 60 stage IV). The schedule of administration was doxorubicin 50 mg/m<sup>2</sup> by intravenous (i.v.) 30 min injection on day 1 followed the day after by docetaxel 75 mg/m<sup>2</sup>, by i.v. 60 min infusion. Cycles were repeate…
Treatment of metastatic breast cancer with vinorelbine and docetaxel.
Objective: A phase II study was performed to evaluate efficacy and safety of the combination vinorelbine and docetaxel in patients with metastatic breast cancer previously treated with anthracycline-based regimens. Overall 41 patients were included in the study. Methods: Treatment consisted of vinorelbine 25 mg/m 2 and docetaxel 75 mg/m 2 , both administered on day 1 every 3 weeks for a maximum of 9 cycles. Most patients (92%) were postmenopausal with a median age of 57 years, and median ECOG performance of 1. Sites of disease were viscera in 42% of patients, bones in 30%, soft-tissues in 32%. Sixty-five percent of patients had >2 metastatic sites. Previous treatments included neo-adjuvant …
Cisplatin plus weekly vinorelbine versus cisplatin plus vinorelbine on days 1 and 8 in advanced non-small cell lung cancer: a prospective randomized phase III trial of the G.O.I.M. (Gruppo Oncologico Italia Meridionale).
Summary Purpose A phase III randomized trial was carried out to compare two schedules of the vinorelbine (VNR)–cisplatin (CDDP) regimen in patients with locally advanced unresectable poor prognosis stage IIIB or metastatic stage IV non-small cell lung cancer. The primary endpoints were overall survival (OS) and analysis of toxicity, while secondary endpoints included response rates, time-to-progression (TTP) and quality of life (QoL). Patients and methods Eligible patients were randomized to receive: (a) VNR 25 mg/m 2 on day 1, 8 and 15 plus CDDP 100 mg/m 2 on day 1 every 4 weeks or (b) VNR 30 mg/m 2 on day 1 and 8 plus CDDP 80 mg/m 2 on day 1 every 3 weeks. All patients were chemotherapy-n…