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.

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.

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.

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.

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.

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.

[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.

[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.

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.

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.

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.

Local estrogen formation by nontumoral, cirrhotic, and malignant human liver tissues and cells.

We have investigated the activity and expression of aromatase enzyme in nontumoral, cirrhotic, and malignant human liver tissues and cells using both chromatographic and reverse transcription (RT)-PCR analyses. After 24- and 72-h incubation of tissue minces or hepatic cell lines with either testosterone or androstenedione as androgen precursor, human hepatocellular carcinoma (HCC) tissues and HepG2 hepatoma cells showed elevated aromatase activity, with estrogen formation rates being 20 and >95%, respectively, as opposed to nontumoral hepatic tissues and nonmalignant Chang liver (CL) cells, where no aromatase activity could be detected. Cirrhotic samples exhibited intermediate enzyme activity. Notably, exposure of HepG2 cells to the aromatase inhibitor Letrozole resulted in a striking decrease of estrogen formation, which became virtually absent at a Letrozole dose of 0.4 nM. RT-PCR analysis revealed markedly lower aromatase mRNA in both CL cells and nontumoral liver tissues, as compared with HepG2 cells and HCC samples. Cirrhotic specimens displayed variable transcript levels, in turn comparable with those observed in nontumoral or HCC tissues. Exon-specific RT-PCR showed prominent expression of exon I.3A-containing message and exon I.4-containing message in CL and HepG2 cells, as in nontumoral and HCC tissues, respectively. The present evidence implies that locally elevated estrogen formation in malignant human liver tissues and cells may have a role in the development and/or maintenance of human HCC, eventually leading to develop alternative strategies for treatment of HCC patients using antiaromatase agents.

Primary chemotherapy with epirubicin and vinorelbine in women with locally advanced breast cancer.

BACKGROUND: To assess the activity and toxicity of primary chemotherapy with epirubicin (60 mg/m2 every other week) and vinorelbine (25 mg/m2, weekly) plus granulocyte colony-stimulating factor (G-CSF) for 12 weeks, in patients with locally advanced breast cancer in a multicenter setting. PATIENTS AND METHODS: Patients with stage IIIA or IIIB breast cancer, not older than 70, were eligible. A two-stage phase II design was applied. Response was assessed clinically, instrumentally and pathologically. RESULTS: Out of 48 enrolled patients, 87.5% received all planned cycles, with a median dose-intensity of 30 mg/m2/week for epirubicin and 23.8 mg/m2/week for vinorelbine. A clinical or instrumental objective response was reached in 42 patients (87.5%, exact 95% CI: 74.7-95.3); significant downstaging was reached in all but one patient; 6 cases had a pathological complete response in the breast, and 2 cases in the lymph nodes too (pathological complete response rate 4.2%, exact 95% CI: 0.5-14.2); a further 2 patients had only microscopic cancer foci at pathological examination of the breast. Radiological tests underestimated the treatment effect on the breast. Toxicity was mild, neutropenia being the most frequent (grade 3-4 in 47% of patients), but never complicated with fever or sepsis. Mild constipation (< or =grade 2) occurred in 35% of patients. Moderate to severe asthenia occurred in 12% of 6 patients. No cardiac toxicity was reported. At 3 years, disease-free survival was 68% and overall survival 81%. CONCLUSION: Primary chemotherapy with epirubicin every other week, weekly vinorelbine and G-CSF support is highly active and well tolerated in patients with locally advanced breast cancer.

Tissue content of hydroxyestrogens in relation to survival of breast cancer patients.

PURPOSE: The main goal of our study was to assess estrogen contents of breast tumor tissues, having different estrogen receptor status, in relation to long-term follow-up of patients. EXPERIMENTAL DESIGN: Twenty-one breast cancer cases, all collected from January 1986 to January 1988 at the M. Ascoli Cancer Hospital Centre in Palermo, were included in the study and compared with 6 healthy women as a control group. Average follow-up time of patients was 144 +/- 10 months. The estrogen receptor status of tissues was determined by both ligand binding and immunohistochemical assays. A high performance liquid chromatography-based approach, jointly with gas chromatography/mass spectrometry, was used to identify and measure main estrogens, various hydroxyestrogens, and their methoxy derivatives in both normal and tumor tissues. RESULTS: Although variable concentrations of hydroxylated estrogens were detected, they consistently accounted for >80% of all of the estrogens. Significantly greater amounts of both 2- and 4-hydroxyestradiol, along with a marked increase of 16 alpha-hydroxyestrone (OHE(1)), were observed in cancer with respect to normal breast tissues. A significant positive association was observed with elevated 16 alpha OHE(1) (P = 0.015) in patients alive, leading to significantly lower (P = 0.043) 2OHE(1):16 alpha OHE(1) ratio values. Conversely, ratio values of 4:2 hydroxy+methoxy estrogens was significantly lower (P = 0.006) in deceased patients. Using cutoff values of 1.2 for 4:2 hydroxy+methoxy ratio and 150 fmol/mg tissue for 16 alpha OHE(1) we achieved a clear-cut separation of patients, with over-cutoff patients having 147 months and under cutoff patients showing only 47 months median survival time (P = 0.00008). CONCLUSIONS: Our data imply that individual hydroxyestrogens may have a distinct role in the onset and the clinical progression of breast cancer, with greater 16 alpha OHE(1) levels being in turn associated to cancer with respect to normal tissues and to a prolonged survival of breast cancer patients.

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 related to their survival characteristics. A significant correlation (P = 0.011) between HER2/neu +3 and estrogen receptor-negative cases was observed in the 487 M0 patients. In addition, HER2/neu +3 cases were associated with a positive nodal status (57.4%), although this association was not quite significant (P = 0.06). More importantly, follow-up data revealed that, in the 91 M0 patients with an average follow-up period of 37 months, the percentage of HER2/neu +3 patients who relapsed was remarkably greater (54.8%) than that observed for the HER2/neu +1/0 cases when combined (34.2%). Furthermore, the disease-free interval (DFI) was 47 months in the HER2/neu +1/0 group, while it dropped to 45 months in c-HER2/neu +3 cases. Although the limited number of cases does not allow us to draw any definitive conclusions, our data suggest that high expression levels of HER2/neu +3 are associated with an early relapse and a shorter disease-free interval in M0 breast cancer patients.

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 intratissue 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 status. In particular, we showed that, with hydroxyestrogens representing the majority of all tissue estrogens, concentrations of individual metabolites, as well as their ratios, significantly differ when comparing normal tissue with cancer tissues or when they are related to the overall survival of cancer patients.

Paclitaxel and epidoxorubicin or doxorubicin versus cyclophosphamide and epidoxorubicin as first-line chemotherapy for metastatic breast carcinoma: a randomised phase II study.

Fifty-eight patients with metastatic breast cancer were randomly treated with a combination of cyclophosphamide 500 mg/m2 on days 1 and 2 plus epidoxorubicin 90 mg/m2 on day 1 every 3 weeks (group A = 18 patients), or paclitaxel 175 mg/m2 cycle plus doxorubicin 50 mg/m2/cycle every 3 weeks (group B = 20 patients), or paclitaxel as above plus epidoxorubicin 90 mg/m2/cycle every 21 days (group C = 20 patients). The trial was designed as a randomized, multi-institutional phase II study where the cyclophosphamide/epidoxorubicin regimen represented the calibration arm. The overall response rate was 50% (95% CL 26-74%) for arm A, 65% (95% CL 41-85%) for arm B and 70% (95% CL 46-88%) for arm C. The complete response rate was 6% for arm A, 10% for arm B and 15% for arm C. Although this trial was non comparative, the median duration of response and median overall survival were almost superimposable in all arms. The taxane-based regimens were associated with significant neurotoxicity in nearly 20% of cases, while febrile neutropenia represented the most severe side-effect. Our data suggest that the anthracycline/taxane combinations are more effective than the epidoxorubicin/cyclophosphamide regimen, at least in terms of objective response rates. These regimens may represent the treatment of choice when oncologists are faced with aggressive visceral metastatic breast cancer in non elderly women.

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.v.) infusion, followed 45 min later by l-OHP 130 mg/m2 i.v. as 2-h venous infusion on 1 day every 3 weeks. All patients had histologically proven metastatic colorectal cancer, age 18-75, measurable disease and normal baseline biological values. Most patients (60%) had >2 disease sites. All patients were assessed for safety and also for response according to an intent-to-treat fashion. RESULTS: The overall response rate was 29% (95% CL 16%-44%) including one CR (2%) and 12 PR (27%). Six patients (16%) showed a stabilization of disease for a tumor growth control rate of 45%. The median time to progression was 4 months (range 1-12+) and median overall survival was 9 months (range 1-29+). CONCLUSION: These data confirm that this oxaliplatin/raltitrexed combination is effective against metastatic colorectal carcinoma, well tolerated with low grade toxicity and easy to administer. Further evaluation of this regimen seems warranted as an alternative to fluoropyrimidine-based combinations.

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. Systemic treatment with single agents and with polychemotherapy, with or without cytokine-based immunotherapy, has not been successful, obtaining very low response rates without a significant benefit in overall survival. This review highlights the most interesting issues regarding conventional therapeutic strategies, in localized and in advanced disease. New approaches such as monoclonal antibodies, vaccines, gene therapy, angiogenesis inhibitors and allogeneic cell transplantation and their possible clinical applications are also discussed.

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.