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. Here we report on a case of advanced gastric cancer occurring in a 72-year-old man who underwent treatment with capecitabine plus oxaliplatin, achieving a complete response.

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: one group diagnosed in 2004 and a second group in 2005-2006. In the 460 cases of 2004, nodal involvement, receptor status, age at diagnosis and TNM maintained a strong predictive value (p < 0.0001). In this group of patients, overall survival was significantly different according to the HER2 expression levels (p = 0.001). In the second group of patients (941 incident cases in 2005-2006) there was a statistically significant survival difference comparing patients with high levels of HER2 expression treated with trastuzumab versus those untreated (p = 0.006). Our data show that elevated levels of HER2 are a negative prognostic factor. In addition, patients overexpressing HER2 show a significant increase of overall survival when treated with trastuzumab.

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). In particular, ERα66 was detected in nontumoral and, to a lesser extent, in cirrhotic liver tissues, whereas its expression decreased or became undetectable in HCC tissues and cell lines. The ERα46 splicing variant was detected ubiquitously in all samples; interestingly, however, the ERα36 variant was inversely expressed with respect to ERα66, being highest in HepG2 cells, intermediate in Huh7 cells, and lowest in HA22T cells. It is noteworthy that aromatase was correspondingly expressed with ERα36 and inversely related to ERα66. This observation suggests that a switch from ERα66 to a predominant expression of ERα36 may be associated with development and/or progression of human HCC.

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 ß (ERα and ERß) 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%). By contrast, no Aro activity could be detected in non-tumoral tissues and HA22T liver cancer cells. Cirrhotic samples and Huh7 cells exhibited intermediate enzyme activity, with estrogen formation of 4% and 34%, respectively. Markedly lower or undetectable Aro mRNA levels were observed in HA22T cells and non-tumoral liver tissues compared with HepG2 cells and HCC samples. Cirrhotic specimens displayed variable transcript levels. Interestingly, no or low expression of wild-type ERα and ERß could be observed in liver cancer cells and malignant tissues. However, ubiquitous expression of the hERα46 variant and occasional expression of the hERß2/Cx variant were observed in cancer tissues and cells. CONCLUSIONS: It is noteworthy that the pattern of wild-type ERα was inversely related to Aro, whilst AREG expression was consistently associated with that of Aro. This combined evidence suggests that locally elevated Aro activity may increase malignant cell proliferation also through AREG signalling.

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. METHODS: 244 patients with >3 N+ were randomized to receive either four 3-weekly courses of epirubicin (E: 100 mg/m(2), day 1) followed by four 4-weekly cycles of cyclophosphamide, methotrexate and 5-fluorouracil (CMF: 600, 40, 600 mg/m(2), days 1, 8: n = 122) or four 3-weekly courses of paclitaxel (T: 175 mg/m(2), day 1) followed by four 3-weekly cycles of epirubicin and vinorelbine (E: 75 mg/m(2), day 1; V: 25 mg/m(2), days 1, 8: n = 122). After CT, tamoxifen (plus an LH-RH analog in menstruating women) was given to all HOR-positive patients over a period of 5 years. Overall survival (OS) was the primary end point. Relapse-free survival (RFS) and toxicity were secondary end points. RESULTS: At a median follow-up time of 102 months (range 3-146), OS and RFS did not differ significantly between groups (E-CMF vs. T-EV: OS, HR 0.94, 95% CI 0.59-1.48, p = 0.8; RFS, HR 0.86, 95% CI 0.57-1.29, p = 0.45). The lack of any difference between assigned treatments was confirmed by multivariate analysis (E-CMF vs. T-EV: RFS, HR 0.98, 95% CI 0.64-1.48, p = 0.9). The 2 regimens showed different toxicity profiles. In fact, significantly more women assigned to E-CMF were affected by stomatitis (p = 0.001) while significantly more women in the T-EV group developed peripheral neuropathy (p < 0.0001) and musculoskeletal disorders (p < 0.0001). However, side effects were moderate and manageable and no toxic death occurred in either arm of the study. CONCLUSIONS: T-EV was safe and moderately toxic but was not superior to E-CMF.

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. The study included 35 patients, with 31 (88.5%) evaluable for efficacy and 35 (100%) for toxicity. A total of 28 patients (80%) had two or more sites of disease. Overall, 4 complete and 16 partial responses were noted with an overall response rate of 64.5%, with 6 cases of stable and 5 cases of progressive disease. Toxicity was found to be manageable in that the only grade 3-4 side effects recorded were palmar-plantar erythrodysesthesia, 8.5%; mucositis, 2.8%; leucopenia, 12.5%; anemia, 2.8% and AST/ALT, 2.8%. No cardiotoxicity was observed. In conclusion, weekly PLD plus paclitaxel appears to be a well-tolerated and effective approach for metastatic breast cancer patients with a high risk of cardiotoxicity.

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. STUDY DESIGN: We designed a dose-finding study to determine the maximum tolerated dose of gemcitabine plus docetaxel, given on a weekly schedule in metastatic breast cancer previously treated with anthracyclines. Three escalating doses of gemcitabine (900, 1000 and 1100 mg/m2) on days 1 and 8 in combination with a fixed dose of docetaxel, 35 mg/m2 on days 1 and 8 were planned. Dose-limiting toxicity included grade > 3 hematologic toxicity, grade > 2 stomatitis, asthenia, diarrhea or organ-specific toxicity (except alopecia). Dose escalation was stopped if 1 out of 3 patients at any dose level experienced dose-limiting toxicity. RESULTS: Nine patients received a mean of 5.1 (range, 1-9) cycles. Gastrointestinal and leukopenia were the main dose-limiting toxicity. No patient experienced dose-limiting toxicity at dose level 1; at dose level 2, 2 out of 3 patients had dose-limiting toxicity and 3 additional patients treated at dose level 2 confirmed that the maximum tolerated dose had been reached. CONCLUSIONS: The recommended gemcitabine dose in combination with docetaxel (35 mg/m2 for a phase II study) was established at 900 mg/m2.

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 androstenedione (Ad) used as precursor resulted in a large extent of 17betaoxidation of T to Ad (cells: 28-77%; tissues: 35-50%). In malignant liver cell lines, both HA22T and Huh7 cells showed consistent amounts of the 5alpha-reductase enzyme products (18% and 15%, respectively), while 5beta-reductase activity was more pronounced in Huh7 cells (18%) than in HA22T cells (1.8%). Interestingly, a significant extent of estrogen formation could be observed in Huh7 cells (5.4-11.5%), while no aromatase activity could be detected in HA22T cells. In HepG2 cells, along with a relatively high proportion of Ad, estrogens represented the most prominent (50-55%) end product of androgen metabolism, regardless of the precursor used. In liver tissues, equivalent results could be obtained, with a consistent proportion of 17betaoxidation of T to Ad (35-50%) being observed in the majority of samples. However, while normal liver tissue samples exhibited a minor proportion of bioactive androgens (3.4%) with no aromatase products, HCC tissues showed a significant extent of aromatase activity (nearly 20%) with estrogen representing the most prominent metabolic product after 24h incubation with either T or Ad. HCV and alcoholic cirrhotic tissues displayed different patterns of androgen metabolism. The former produced limited amounts of bioactive androgens (5.3%) and considerable levels of the intermediate aromatase product 19OH-Ad (up to 28%), the latter exhibited a prevalence of androgen degradation through the 5beta-reductase pathway (9.8%) and a significant extent of aromatase activity (16% as a whole). In conclusion, three major metabolic states could be depicted, depending on prevalent pathways of androgen metabolism and steroid receptor status: estrogenic, androgenic, and mixed. This model supports the idea that local estrogen biosynthesis may be implicated in human HCC and provides a basis for the exploitation of aromatase inhibitors and/or ER antagonists or selective estrogen receptor modulators (SERMs) as a new therapeutic strategy in HCC patients.

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= 0.882). Endocrine manipulation is the treatment of choice in the case of hormone receptor-positive breast tumors. In 91 receptor-positive DMBC patients the endocrine treatment was associated with a prolonged overall survival (OS) (median survival 33.5 months compared to 29 months for receptor-positive patients who did not receive hormone treatment). Receptor-negative patients who underwent endocrine therapy (76% of cases) survived longer than receptor-negative patients who did not receive hormone treatment (median survival 28.5 months vs. 15 months, respectively). This evidence supports the concept that endocrine therapies impinging upon molecular targets other than hormone receptors may increase survival rates of breast cancer patients.

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. The primary objective is disease-free survival.

[Reports on nine cases of spondylodiscitis]. / Osservazioni su nove casi di spondilodiscite.

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. aureus and, in endemic areas, by Mycobacterium tuberculosis and Brucella spp. We describe 9 cases, from October 2004 to August 2005, all spontaneous diseases occurring in adults (mean age 64 years). The site of infection was lumbar in 7, lumbar-sacral in 1 and dorsal in 1. None were associated to sepsis. The causative bacteria were known in 6 cases (1 BK, 1 S. aureus, 4 Brucella) and unknown in 3 cases. In all cases therapy was only medical. Significant circulation in Sicily of both Mycobacterium tuberculosis and Brucella spp. make those microorganisms the most frequent agents of spondylodiscitis.

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. All patients were chemotherapy-naïve and had an ECOG performance status (PS) of 0-1. RESULTS: Overall 278 patients were enrolled into the trial. Overall response rate was 34% (95% CL 26-42%) in the weekly VNR/CDDP arm, and 32% (95% CL 24-40%) in patients treated with day 1-8 VNR/CDDP without any statistically significant difference. Median TTP was 4.5 and 4.6 months respectively for weekly VNR/CDDP arm and the day 1-8 VNR/CDDP one. This difference was not statistically significant (log-rank test, p=0.818). Median OS was 9.45 and 10 months respectively for weekly VNR/CDDP arm and the day 1-8 VNR/CDDP one without statistically a significant difference (log-rank test, p=0.259). The 1- and 2-year survival rates were 31 and 36%, and 10 and 11% respectively. The incidence of severe neutropenia (34% versus 68%; p=0.0001) and of febrile neutropenia (5% versus 12%; p=0.026), as well as the rate of therapy omissions (10% versus 24%; p=0.0037) were higher in the weekly VNR/CDDP arm than in the day 1-8 VNR/CDDP one. The weekly VNR/CDDP regimen was associated with a lower received dose intensity in a statistically significant fashion (9% versus 22%; p=0.0001) and with a lower non-statistically significant quality of life score as compared to the day 1-8 VNR/CDDP schedule. CONCLUSIONS: The combination of day 1-8 VNR plus CDDP every 3 weeks is less toxic and better tolerated than the regimen of weekly VNR plus CDDP every 4 weeks. The two schedules are equivalent in terms of overall response rate, median time-to-progression and overall survival. The combination of VNR on day 1-8 plus CDDP every 3 weeks may be considered as a reference regimen for the treatment of patients with advanced disease and those who deserve a postoperative therapy, and for future studies.

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. The mainstays of cancer treatment during the twentieth century were surgery, radiation and chemotherapy. However, surgery is not curative in metastatic disease, radiation and chemotherapy are limited by side effects because they can't discriminate between healthy and cancerous cells. When key molecular changes responsible for malignant transformation were identified (e.g. growth factors and their receptors), it was hoped that new targeted agents, by inhibiting cancer-specific pathways, would spare normal cells and thereby offer improved safety benefits and a higher therapeutic index over standard chemotherapeutics. The most common targeted therapies used in clinical practice, i.e. monoclonal antibodies and small molecules, are described.

[EBV reactivation in a patient undergoing chemotherapy for invasive thymoma]. / Riattivazione di EBV in un paziente sottoposto a chemioterapia per metastasi da timoma misto invasivo.

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. In January 2007, after consultation with an infectious disease specialist, the patient was admitted to the oncology department because of bilateral swelling of the parotid glands which was most likely of infectious or mycotic origin and attributed to immunosuppression by chemotherapy (the last cycle was completed on 28th December 2006). During his hospital stay, the patient underwent routine blood tests, serological tests (EBV-VCA IgM/IgG: positive/positive, EBV-EBNA IgG: positive), cultural and instrumental tests. Due to the serological results, we decided to search for EBV in blood by using PCR (23,000 copies/100,000 cells). We hypothesize that EBV infection could have caused both thymoma and bilateral parotiditis. Accordingly, a multidisciplinary approach, including consultation with an oncologist, infectious disease and microbiology specialists, is the best way to manage infectious complications in patients with a deficit of cells-mediated immunity.

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. 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 chemotherapy in 7.3% of cases, adjuvant chemotherapy in 71%, and front-line chemotherapy for advanced disease in 50% of cases. RESULTS: A total of 273 cycles of chemotherapy were delivered (mean 6 cycles/patient). All patients were assessable for toxicity: alopecia was recorded in all patients, grade 2-3 neutropenia in 34% and grade 4 in 9.7%; grade 2-3 nausea/vomiting in 29%, grade 2-3 mucositis in 24.3%. Out of 39 patients evaluable for response, 7 (18%) complete responses and 13 (33%) partial responses have been recorded with an overall response rate of 51%. Six patients (15%) experienced stable disease and 13 patients (33%) progressed. Mean duration of responses was 15.2 months. Median time to progression and median overall survival were 6.2 and 14 months, respectively. CONCLUSION: In patients with metastatic breast cancer previously treated with anthracyclines the combination vinorelbine-docetaxel is very active and well tolerated representing a valid therapeutic option for the management of this patient population.

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. A single treatment cycle comprised 4 weekly infusions followed by 2 weeks of rest. RESULTS: According to an intent-to-treat analysis, a partial response was exhibited in 12 of 60 enrolled patients (20%; 95% confidence interval, 11%-32%) with a median duration of 5.1 months (range, 3-7.4 months). The tumor growth control rate was 50% (95% confidence interval, 37%-63%). Objective responses did not correlate with performance status, number of sites of disease, and pretreatments or epidermal growth factor receptor status. The median progression-free survival was 3.1 months (range, 1.2-9 months), whereas median overall survival was 6 months (range, 2-13 months). Both survival parameters correlated with performance status at the beginning of treatment. The main grade 3/4 toxicities were nausea (33%), diarrhea (27%), leukopenia (18%), asthenia (13%), and acne-like reaction (13%). CONCLUSION: Our data suggest that the weekly irinotecan/cetuximab regimen is feasible in an outpatient setting and tolerated by most patients. At present, combinations of chemotherapy with cetuximab are being evaluated in patients with earlier-stage disease in a number of ongoing studies.

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. From May 1998 to May 2000, 51 patients entered the study. Patients received a median relative dose intensity of 97.5% (range 81-100%). No severe toxicities were observed. Seven patients (14%) experienced neutropenia grade 2. Seven patients (14%) experienced grade 2 anemia. Two patients (4%) experienced severe asthenia. Three out of 50 evaluable patients [6%, 95% confidence interval (CI) 2-12.6%] showed a complete response, whereas 23 (46%, 95% CI 32.2-59.8%) had a partial response, with an overall response rate of 52% (95% CI 38.2-65.8%). In addition, eight patients (15.7%) had stable disease. In the 13 patients untreated for metastatic disease, the overall response rate was 92.3% (CI 77.8-100), with one complete response and 11 partial responses (84.6% CI 65-100%). In the whole group, the median time to progression and overall survival were 8 (range 1-18) and 14 months (95% CI 11-17), respectively. Thus, in metastatic breast cancer patients pre-treated with anthracyclines, the weekly administration of paclitaxel, 5-FU and folinic acid with G-CSF support seems to be extremely tolerable and active.

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. Here we report results of our MeDiet Project, a randomized, dietary intervention study aimed to assess the effect of a Mediterranean diet on the profiles of endogenous estrogens in healthy postmenopausal women. Out of the 230 women who initially volunteered to participate in the study, 115 were found to be eligible and were enrolled. Women were then randomly assigned into an intervention (n = 58) and a control (n = 57) group. Women in the intervention group adhered to a traditional, restricted Mediterranean diet for 6 mo, whereas women in the control group continued to follow their regular diet. Women in the intervention group changed their dietary regimen substantially, and this eventually led to a shift from a prevalent intake of animal fat and proteins to a prevalent intake of vegetable fat and proteins. Regarding urinary estrogens, no significant difference was observed between the intervention and control groups at baseline. After 6 mo, however, control women did not show any major change but women in the intervention group exhibited a significant decrease (over 40%) of total estrogen levels (P < 0.02). The largest part of this modification was based on a marked decrease of specific estrogen metabolites, including hydroxy- and keto-derivatives of estradiol or estrone. To our knowledge, this is the first report to show that a traditional Mediterranean diet significantly reduces endogenous estrogen. This may eventually lead to identify selected dietary components that more effectively decrease estrogens levels and, hence, provide a basis to develop dietary preventive measures for breast cancer.

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 < 0.001), and a significant association between HER2/neu overexpression and estrogen and progesterone receptors status (P < 0.001). In 194 patients without metastasis, with an average follow-up > or =5 years, only HER2/neu 3+ and histopathologic grading G3 were significantly associated with overall survival.

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. Overall response rates (ORR) were 31% in arm A (95% CI, 24.6% to 38.3%) and 34% in arm B (95% CI, 27.2% to 41.5%; P = .60). In both arms A and B, median time to progression (TTP; 7 v 7 months, respectively), duration of response (9 v 10 months, respectively), and overall survival (OS; 14 v 15 months, respectively) were similar, without any statistically significant difference. Toxicity was mild in both groups: alopecia and gastrointestinal disturbances were the most common toxicities in arm A; thrombocytopenia and neurosensorial were the most common toxicities in arm B. Grade 3 to 4 toxicities were uncommon in both arms, and no statistical significant difference was observed. CONCLUSION: There is no difference in ORR, TTP, and OS for patients treated with the FOLFIRI or FOLFOX4 regimen. Both therapies seemed effective as first-line treatment in these patients. The difference between these two combination therapies is mainly in the toxicity profile.