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).

Capecitabine in combination with oxaliplatin as first-line therapy for advanced gastric cancer: a case report.

Gastric cancer is one of the most common cancers worldwilde. The five-year survival for stage IV gastric cancer is around 5-10% in Western countries. Advanced gastric cancer is sensitive to numerous agents, but there is no generally accepted standard regimen.

Estrogen signalling through amphiregulin may be implicated in human hepatocellular carcinoma.

Background: We investigated aromatase (Aro)-driven estrogen formation in non-tumoral and malignant liver tissues and cells, also in relation to expression of the estrogen receptors α and β (ERα and ERβ) and amphiregulin (AREG), aiming to gain insights into the potential role of estrogens in human hepatocellular carcinoma (HCC).

Materials And Methods: Chromatographic and reverse transcriptase polymerase chain reaction (RT-PCR) analyses were used to assess activity and expression of the Aro enzyme and AREG as well as the expression of wild-type and variant ERs, both in vivo and in vitro.

Results: Following 24 h and 72 h incubation of liver tissues or cells with testosterone, human HCC tissues and HepG2 hepatoma cells showed elevated Aro activity (estrogen formation, respectively, of 20% and 52%-99%).

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 reaction (RT-PCR).

Weekly pegylated liposomal doxorubicin and paclitaxel in patients with metastatic breast carcinoma: A phase II study.

Pegylated liposomal doxorubicin (PLD) has the advantage of delivering active anthracycline directly to the tumor site, while exposing the patient to a lesser degree of doxorubicin-associated toxicities. Recently, a regimen in which paclitaxel is infused weekly over 1 h produced substantial antitumor activity with little myelosuppression. We designed a phase II trial to study the efficacy and toxicity of 10 mg/m(2) PLD on Days 1, 8 and 15, plus 70 mg/m(2) paclitaxel weekly in patients with untreated metastatic breast cancer and a high risk of cardiotoxicity.

Epirubicin followed by cyclophosphamide, methotrexate and 5-fluorouracil versus paclitaxel followed by epirubicin and vinorelbine in patients with high-risk operable breast cancer.

Objective: Breast cancer patients with >3 involved nodes (N+) have a poor outcome. Chemotherapy (CT), alone or combined with endocrine therapy (ET) in hormone receptor (HOR)-positive patients, is the standard for these women. However, there are still questions surrounding the optimal adjuvant CT regimen.

Docetaxel and gemcitabine in the treatment of metastatic breast carcinoma: a dose finding study.

Aims And Background: Patients with metastatic breast cancer previously treated with anthracyclines for advanced disease are usually refractory to any further treatment with anthracyclines and have a poor prognosis. Therefore, new drugs or new combinations of drugs are needed. One approach has been to focus on the type of chemotherapy with low toxicity that preserves quality of life during treatment, such as weekly drug administration.

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.

Endocrine therapy in metastatic breast cancer: data from Breast Cancer Registry of Palermo, 1999-2005 .

This study compares the survival of breast cancer patients who are metastatic at diagnosis (DMBC) and of recurrent metastatic breast cancer (RMBC) patients. We analyzed retrospectively the population-based data of Breast Cancer Registry of Palermo and collected a total of 4459 breast cancer cases in the years 1999-2005. Survival analysis did not show statistically significant differences between DMBC and RMBC patients (P= 0.

The management of cancer in the elderly: targeted therapies in oncology.

Cancer is universally considered a disease of ageing. Today the management of elderly cancer patients poses many specific problems and it should be revisited in the light of the most recent advances in both diagnosis and treatment of human malignancies. In particular, the potential use of novel therapeutic options, based on therapeutic agents raised against molecular targets (the so called targeted therapy), appears to be promising in this clinical settings especially in view of the limited side-effects.

Multicentric, randomized phase III trial of two different adjuvant chemotherapy regimens plus three versus twelve months of trastuzumab in patients with HER2- positive breast cancer (Short-HER Trial; NCT00629278).

Trastuzumab, a monoclonal antibody against the HER2 receptor, is currently approved as a part of adjuvant therapy for patients with HER2-overexpressing breast tumors. The Short-HER study is a phase III randomized, multicentric Italian trial aimed at testing the optimal duration of adjuvant trastuzumab. In this trial, 2500 patients with HER2-positive breast cancer will be randomized to receive the following: (arm A, long) 4 courses of anthracycline- based chemotherapy (doxorubicin/cyclophosphamide or epidoxorubicin/cyclophosphamide) followed by 4 courses of docetaxel or paclitaxel in combination with trastuzumab, followed by 14 additional courses of trastuzumab administered every 3 weeks (for a total of 18 3-weekly doses of trastuzumab); or (arm B, short) 3 courses of 3-weekly docetaxel in combination with weekly trastuzumab (for a total of 9 weekly doses of trastuzumab) followed by 3 courses of 5-fluorouracil/epirubicin/cyclophosphamide.

[Reports on nine cases of spondylodiscitis].

Spondylodiscitis is an infection of the intervertebral disk and the adjacent vertebrae, with or without associated epidural or psoas abscesses. It is a serious disease both due to its long-term course and the possible outcomes. It is frequently caused by S.

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).

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 25mg/m(2) on day 1, 8 and 15 plus CDDP 100mg/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.

[EBV reactivation in a patient undergoing chemotherapy for invasive thymoma].

Over the last few years evidence has emerged to indicate the involvement of herpes viruses in several infectious complications observed in patients undergoing antiblastic chemotherapy. We present a case of bilateral parotiditis due to EBV reactivation in a patient who had received chemotherapy because of an invasive thymoma. In October 2006, a 53-year-old man with pulmonary and pleural metastases owing to an invasive thymoma, was started on chemotherapy with cisplatin, adriamycin and cyclophosphamide.

A traditional Mediterranean diet decreases endogenous estrogens in healthy postmenopausal women.

Breast cancer incidence and mortality rates are markedly lower in the south than in the north of Europe. This has been ascribed to differences in lifestyle and, notably, dietary habits across European countries. However, little information exists on the influence of different dietary regimens on estrogens and, hence, on breast cancer risk.

HER2/neu expression in relation to clinicopathologic features of breast cancer patients.

We have evaluated HER2/neu expression in 1,355 breast cancer patients recruited at the Breast Cancer Registry in Palermo between January 1999 and December 2004. In this retrospective study, HER2/neu expression was related to clinicopathologic features of the disease, including tumor size, nodal and menopausal status, estrogen and progesterone receptors. Statistical analysis on all 1,355 patients showed a significant correlation between HER2/neu and nodal status (P < 0.

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/m2 and docetaxel 75 mg/m2, both administered on day 1 every 3 weeks for a maximum of 9 cycles.

Efficacy and safety of cetuximab/irinotecan in chemotherapy-refractory metastatic colorectal adenocarcinomas: a clinical practice setting, multicenter experience.

Background: 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/m2 as a 1-hour intravenous infusion and cetuximab 400 mg/m2 infused over 2 hours as the initial dose and 250 mg/m2 infused over 1 hour for the subsequent administrations.

Weekly paclitaxel, 5-fluorouracil and folinic acid with granulocyte colony-stimulating factor support in metastatic breast cancer patients: a phase II study.

We conducted a phase II study to determine the activity and tolerability of weekly paclitaxel, 5-fluorouracil (5-FU) and folinic acid plus granulocyte colony-stimulating factor (G-CSF) support in anthracycline-pre-treated or -resistant metastatic breast cancer patients. The phase II study was designed following the Simon optimal-two stage method. Patients received paclitaxel 80 mg/m, folinic acid 10 mg/m and bolus infusion of 5-FU 300 mg/m every week plus G-CSF on day 3 for 24 consecutive weeks in the absence of disease progression.

Phase III randomized trial of FOLFIRI versus FOLFOX4 in the treatment of advanced colorectal cancer: a multicenter study of the Gruppo Oncologico Dell'Italia Meridionale.

Purpose: We performed this phase III study to compare the irinotecan, leucovorin (LV), and fluorouracil (FU) regimen (FOLFIRI) versus the oxaliplatin, LV, and FU regimen (FOLFOX4) in previously untreated patients with advanced colorectal cancer.

Patients And Methods: A total of 360 chemotherapy-naive patients were randomly assigned to receive, every 2 weeks, either arm A (FOLFIRI: irinotecan 180 mg/m(2) on day 1 with LV 100 mg/m(2) administered as a 2-hour infusion before FU 400 mg/m(2) administered as an intravenous bolus injection, and FU 600 mg/m(2) as a 22-hour infusion immediately after FU bolus injection on days 1 and 2 [LV5FU2]) or arm B (FOLFOX4: oxaliplatin 85 mg/m(2) on day 1 with LV5FU2 regimen).

Results: One hundred sixty-four and 172 patients were assessable in arm A and B, respectively.

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.

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.

Activity and toxicity of oxaliplatin plus raltitrexed in 5-fluorouracil refractory metastatic colorectal adeno-carcinoma.

Background: This study evaluated the antitumor efficacy and safety of a novel oxaliplatin/raltitrexed combination in pretreated advanced colorectal cancer patients.

Patients And Methods: Forty-five patients with 5-fluorouracil-refractory metastatic colorectal cancer received raltitrexed 3.0 mg/m2 as a 15-minute intravenous (i.

Renal cancer treatment: a review of the literature.

Renal carcinoma represents about 3% of all adult tumors, with an estimate of 31,900 new cases diagnosed in 2003 in the United States. In the early phase of its natural history, renal cancer is potentially curable by surgery, but if the disease presents any signs of metastasis, the chances of survival are remote, even though anecdotal cases characterized by long survival have been reported. In fact, the treatment of metastatic renal cancer remains unsatisfactory.